Within days of acclimatization, however, Q normalizes following an unexplained reduction in stroke volume (SV). To investigate whether the altitude-mediated reduction in plasma volume (PV) and hence central blood volume (CBV) is the underlying mechanism we increased/decreased CBV by means of passive whole body head-down (HDT) and head-up (HUT) tilting in seven lowlanders at sea level (SL) and after 25/26 days of residence at 3454 m. Prior to the experiment on day 26, PV was normalized by infusions of a PV expander. Cardiovascular responses to whole body tilting were monitored by pulse contour analysis. After 25/26 days at 3454 m PV and blood volume decreased by 9 ± 4% and 6 ± 2%, respectively (P < 0.001 for both). SV was reduced compared to SL for each HUT angle (P < 0.0005). However, the expected increase in SV from HUT to HDT persisted and ended in the same plateau as at SL, albeit this was shifted 18 ± 20° toward HDT (P = 0.019). PV expansion restored SV to SL during HUT and to an ∼8% higher level during HDT (P = 0.003). The parallel increase in SV from HUT to HDT at altitude and SL to a similar plateau demonstrates an unchanged dependence of SV on CBV, indicating that the reduced SV during HUT was related to an attenuated CBV for a given tilt angle. Restoration of SV by PV expansion rules out a significant contribution of other mechanisms, supporting that resting SV at altitude becomes reduced due to a hypovolemia.During acute altitude exposure tachycardia increases cardiac output (Q) thus preserving systemic O All were physically active but not involved in elite sport. To avoid influence from previous hypoxic exposure persons that had traveled to altitudes >2000 m within the last 4 weeks before the onset of the study were excluded.The baseline study period at SL lasted 5 weeks and included four measurements of intravascular volumes by carbon monoxide (CO) rebreathing, all of them separated by 7–12 days, assessment of resting pulmonary artery pressure by Doppler echocardiography and the first tilt table experiment.At the onset of the altitude period subjects were transported by train to the Jungfraujoch research station which offers bedrooms, kitchen facilities, and living space with normal room temperatures. The sojourn lasted 4 weeks over which the subjects did not descend below the altitude of the station. They maintained their usual physical activity by hiking, mountaineering activities, and exercising on a cycle ergometer. Subjects were encouraged to pursue their habitual diet for which they ordered their desired groceries. During the altitude period, duplicate measurements of intravascular volumes were performed after 2 and 3 weeks and Doppler assessments of pulmonary artery pressure after 3 weeks. The tilt table experiments were repeated after 25 and again after 26 days at altitude. Prior to the last tilt table experiment blood volume was restored to baseline levels by intravenous infusion of isotonic Dextran solution .After the altitude period subjects were transported back to Zurich by train.Intravascular volumes were determined by a modified version of the CO rebreathing protocol of Burge and Skinner . After t2 through an open circuit from a Douglas bag for 4 min to eliminate N2 from the airways. Thereafter, the breathing circuit (previously O2 flushed) was closed by a sliding valve. After a few breaths a priming dose (20 mL) of 99.997% chemically pure CO  was administrated as a bolus and rebreathed for 10 min while a soda lime container eliminated CO2 from the circuit. At the end of this period, 2 mL of venous blood was sampled and analyzed in quadruplicate for percent carboxy-hemoglobin (%HbCO) and [Hb] in a hemoximeter . Furthermore, hematocrit was determined by the micromethod . While the subjects remained connected, the rebreathing circuit was then flushed with pure O2 and the main CO dose was administered (1.2 mL/kg bodyweight) and rebreathed for 10 min. Thereafter, a second 2 mL blood sample was obtained and analyzed. The change in %HbCO between the first and second blood sample (ΔHbCO) was used for calculation of total hemoglobin mass , taking into account the ∼2.2% of CO remaining in the rebreathing circuit at the end of the rebreathing period (Burge and Skinner Subjects then breathed pure OTo account for the reduced barometric pressure the CO doses were increased to 30 mL (priming dose) and 1.5 mL/kg (main dose) during the altitude period. All CO rebreathing tests were performed by the same operator as duplicate measurements on subsequent days. The typical measurement errors (SD of difference scores/√2) for blood volume, red cell volume and PV, assessed from the first duplicate measurement at SL, were 2.6%, 1.6%, and 3.3%, respectively.The here reported SL values for intravascular volumes correspond to the average over the four duplicate measurements conducted during the baseline period. Similarly, the intravascular volumes at altitude correspond to the average over the duplicate measurements conducted after 2 and 3 weeks.Subjects rested in the supine position on the tilt table with their feet strapped into a retainer. A fixed bicycle saddle was adjusted to support their body weight during HUT. After 5 min in the horizontal position the subjects were tilted to −90°, −60°, and −30°  and to 15°, 30°, and 60° , respectively, remaining in each position for 3 min. The order of the positions was randomized but HUT was always alternated with HDT, and vice versa.Throughout the tilt table experiments mean finger arterial pressure was measured by the volume clamp method as the integral over one heart beat . HR was the inverse of the inter beat interval. SV was determined by a three-element model of arterial input impedance  incorporating age, sex, height, and weight from the blood pressure waveform  was performed in the supine position at SL and after 3 weeks at altitude. Systolic pulmonary artery pressure was estimated from the peak tricuspid regurgitation jet velocity, using the simplified Bernoulli equation and combining this value with an estimate of the right atrial pressure. Right atrial pressure was estimated from the inferior vena cava diameter and respiratory changes  prior to each assessment of intravascular volumes, with the subjects supine. The here reported SL values correspond to the average over all measurements conducted during the baseline period whereas the altitude values correspond to the average over the measurements conducted prior the CO rebreathings performed after 2 and 3 weeks at altitude.t-tests. Statistics were performed using SAS 9.3.  and Sigmaplot 11.0 . A P-value <0.05 was considered as statistically significant.The hemodynamic responses to the tilt table experiments at the different time points were compared by application of a general linear model (GLM) with Tukey–Kramer post hoc test. For the analysis the data were categorized as HUT, supine, and HDT.The tilt angle at which a plateau in SV was reached over the range from HUT to HDT was estimated by a two-segment linear regression analysis that determined the tilt angle at which the breakpoint between the two regression lines was located.Changes in intravascular volumes, blood pressure, and pulmonary artery pressure from SL to altitude were evaluated by paired During the baseline period weekly blood withdrawals for the experiments reported here and for other study purposes ranged from 4–50 mL. At altitude another 10–65 mL/week were withdrawn. The total volume of blood withdrawal was ∼150 mL over the baseline period and ∼180 mL over the altitude period.P = 0.006 vs. first measurement) but had normalized 1 week later. At altitude, no differences in either blood volume, PV, or red cell volume were observed between the measurements conducted after 2 and 3 weeks. The results obtained at SL and altitude were then averaged for comparison (Table P < 0.001 for both) while red cell volume remained unchanged. As a result, [Hb] and hematocrit both increased at altitude.The four duplicate CO rebreathings at SL revealed no significant changes in blood volume and red cell volume whereas PV was increased by 6% 2 weeks before the onset of the altitude period  that led to a plateau where after SV remained independent of the tilt angle  but not in the supine position (P = 0.3) or during HDT (P = 0.7). Two-segment linear regression indicated that, at SL, the onset of the SV plateau was located at a tilt angle of 0.8 ± 9° (P = 0.9 vs. supine position) whereas, at altitude, it was shifted 18 ± 20° toward HDT (P = 0.019).In all tilt table experiments, we observed a similar increase in SV from HUT to HDT P < 0.000 that ledP = 0.003; supine position, P = 0.04; HUT, P < 0.0001) . The onset of the SV plateau had reverted to a tilt angle that was not significantly different from the supine position .Normalization of blood volume increased SV in all tilt positions . The PV expansion did not affect HR during HDT but flattened the HR response to HUT (P = 0.04)  than at SL (4) Table .Cardiac output always remained unaffected by changes in tilt position. At altitude, Q was similar to SL whereas PV expansion increased Q throughout all tilt angles.P = 0.047 and P = 0.03).According to the volume clamp method both systolic and diastolic blood pressures were reduced at altitude and partially restored by the PV expansion. In all conditions systolic blood pressure remained unaffected by changes in tilt angle whereas diastolic blood pressure tended to be lowest in the supine position and increase toward both HUT and HDT. In contrast, oscillometry indicated a slight increase in blood pressure from SL to altitude with systolic and diastolic pressures raising from 126 ± 7 to 132 ± 6 mmHg and from 68 ± 6 to 73 ± 6 mmHg, respectively (P = 0.005).Systolic pulmonary artery pressure was 17.4 ± 4.3 mmHg at SL. After 3 weeks of altitude exposure it had increased to 25.2 ± 5.8 mmHg (P = 0.019). Normalization of PV at altitude restored SV to SL during HUT and to ∼8% higher levels during HDT.We investigated the contribution of hypovolemia to the reduction in SV at altitude. After 3 weeks at 3454 m blood volume had decreased by 6% due to a 9% PV contraction. SV during HUT was lower than at SL but the increase toward the supine position, and the plateau that was eventually reached, were similar. At SL the onset of the SV plateau was located in the supine position whereas it was shifted 18 ± 20° toward HDT at altitude  defines and maintains the diameter at which the finger artery is clamped, keeping transmural vascular pressure across the finger arterial wall constant during the measurement. As long as constancy of transmural vascular pressure is maintained, environmental barometric pressure does not affect vascular compliance. In this regard it is important to note that, in a previous validation of Modeflow determination of SV/Q, simulation of a systematic offset in blood pressure over a range of 20 mmHg did only minimally affect the measurement of SV/Q (Wesseling et al. Over the course of the study we repeatedly collected blood for experimental purposes. At altitude the blood withdrawal conformed to ∼3% of the initial red cell volume and may have offset the 2.5–5% increase in red cell volume that can be expected to occur during 3 weeks at ∼3500 m (Rasmussen et al. In conclusion our results indicate that a lower blood volume is the mechanism responsible for the reduced resting SV at 3454 m altitude whereas myocardial contractility is preserved. The complete restoration of SV to or above baseline levels after normalization of PV rules out contribution of mechanisms other than hypovolemia.


This study investigated the effect of proximity to city parks on blood pressure categories during the first trimester of pregnancy. This cross-sectional study included 3,416 female residents of the city of Kaunas, Lithuania, who were enrolled in the FP7 PHENOTYPE project study. The women were classified into four blood pressure categories: optimal, normal, high-normal blood pressure, and hypertension. Multinomial regression models were used to investigate the association between three women’s groups with respect to the residence distances from city parks  and four blood pressure categories. When using the optimal blood pressure as the reference group, the crude and adjusted odds ratios (OR) for normal blood pressure and for high-normal blood pressure proved to be statistically significantly higher after the inclusion of the selected covariates into the regression analysis. The probability of normal blood pressure increased by 9%, and that of high-normal blood pressure—by 14% for every 300 m increase in the distance to green spaces. The findings of this study suggest a beneficial impact of nearby city parks on blood pressure amongst 20- to 45-year-old women. This relationship has important implications for the prevention of hypertension and the reduction of hypertension-related morbidity. Environmental exposures have long been suspected to have an independent influence on health outcomes, particularly in terms of cardiovascular disease and hypertension—the second leading cause of chronic diseases worldwide ,2,3,4. BThere is little research on the association between air pollution exposure with blood pressure levels in early pregnancy ,8, but tAssessments of the relationships between exposure to natural outdoor environments and blood pressure are sparse, and the associations with the effects of different blood pressure categories remain uncertain ,4,13,22;www.phenotype.eu [This study was conducted as part of the Positive Health Effects of the Natural Outdoor Environment in Typical Populations in Different Regions in Europe (PHENOTYPE) project funded by the European Commission Seventh Framework Programme (otype.eu ). The stotype.eu .To our knowledge, this is the first study to examine the association between green space and blood pressure groups in early pregnancy. In this paper, we hypothesised that the impact of green space on blood pressure amongst women depends on the proximity of the place of residence from the city park. Furthermore, we explored whether the associations of city park proximity differed in four blood pressure categories among the studied women, while controlling for confounding variables. www.phenotype.eu [This cross-sectional study was a part of a larger project on health effects of the natural outdoor environment (otype.eu ). The paotype.eu . The womThe study participants’ blood pressure was measured by a well-trained physician. The blood pressure measurements were taken in a seated position, after five minutes of rest, using a mercury column sphygmomanometer placed on the right arm. The mean value of two blood pressure readings—systolic (SBP) and diastolic (DBP) blood pressure levels—over a two-minute interval was documented for each participant. The estimation of the blood pressure category was based on at least two blood pressure readings taken on two separate occasions. At baseline examination, women were classified into one of the four blood pressure categories based on the ESH-ESC 2007criteria: optimal (SBP < 120 mm Hg and DBP < 80 mm Hg), normal (SBP 120 to 129 mm Hg or DBP 80 to 84 mm Hg), high-normal blood pressure (SBP 130 to 139 mm Hg or DBP 85 to 89 mm Hg), and hypertension (SBD ≥ 140 or DBP ≥ 90 mm Hg) . The nor2). The respondents’ perceived stress was measured by a question: “My daily activities are very trying and stressful”. The four response options were: “this describes me very well” (1), “fairly well” (2), “not very well” (3), or “not at all” (4), were scored with 1–4 points, and were used to define stress. Values 1 and 2 were considered to represent “stress”, and values 3 or 4—“no stress”.Pregnant women were asked to complete questionnaires provided to them at the clinic. The interview queried women regarding demographics, chronic diseases , and duration of residence. Women reported their age at inclusion (less than 30 years or 30 years and older), education , social status , marital status , smoking (non-smoker or smokes at least one cigarette per day), alcohol consumption (0–1 drinks per week or 2 and more drinks per week), and other potential risk factors for hypertension. Body mass index (BMI)  was calculated as weight (kg) divided by height squared  and locations .We used GIS to estimate the distance to the nearest park for 3,416 women at their current residential address. We determined three green space distance categories to the nearest park, using circular buffers with a radius of <300 m, 300–1,000 m, and >1,000 m around each woman’s place of residence. This choice was selected on the basis of European guidelines for access to recreation green spaces , and on p < 0.05) to the outcome were treated as possible risk factors for hypertension, and were included in the multinomial regression models. Multinomial regressions were used to assess the relationship between green space proximity as a categorical variable and as a continuous variable, and the blood pressure categories, adjusting for age, education, socioeconomic position, passive smoking, BMI, chronic disease, parity, and stress. The optimal blood pressure group was used as the reference group. The effects of green space on doctor-diagnosed blood pressure categories were estimated as crude and adjusted odds ratios (OR) with 95% confidence intervals (CI). All statistical analyses were performed using SPSS version 18.0 . We used chi-square tests to compare the values and frequencies of baseline characteristics by the blood pressure category of the women. Predictor variables whose univariate test showed a statistically significant association (p < 0.05): education, marital status, socio-economic status, BMI, parity, passive smoking, chronic disease, and stress. We treated these variables as possible risk factors for hypertension. In this cross-sectional study, 3,416 women had complete blood pressure data and could be geocoded according to their residential address. The women who participated in the study were predominantly Lithuanian by their ethnic origin (97.4%), and were non-smokers (93.2%). The mean age was 28.4 years, and the women tended to be well-educated (54.6% of them—with a university degree). The prevalence of hypertension was 14.0%. Study participants were evenly distributed by distance to green spaces according to age, marital status, maternal stress, education, smoking, ethnicity, and other variables, but not for parity. The proportion of women with optimal blood pressure tended to be higher in the area nearest to the park (26.3%) than in the farthest area (20.9%), while the proportion of women with high-normal blood pressure tended to be higher in the area farthest to the park than in the nearest to the park area . Overweight and maternal stress tended to increase with increasing distance between the place of residence and the nearest city park.vs. the nearest distance to city parks. We did not find any statistically significant association between the proximity of city parks and the hypertension group: the crude ORs were 1.00, 95% CI 0.77–1.33 and 1.18, 95% CI 0.81–1.72, respectively, for moderate and the farthest distance vs. the nearest distance to city parks.In univariate analysis (crude OR), distance to green spaces was positively related to the normal blood pressure category, compared to the reference category . With increasing distance to city parks, the increase in the odds ratios for high-normal blood pressure was statistically significant; the crude ORs were 1.12, 95% CI 0.82–1.52 and 1.83, 95% CI 1.22–2.75, respectively, for moderate and the farthest distance vs. the nearest distance, respectively). The association between the proximity of city parks and the hypertension group was not statistically significant: the adjusted ORs were 1.18, 95% CI 0.79–1.77 for the farthest vs. the nearest distance, accordingly. The analysis of park proximity as a continuous variable also showed statistically significant results for the normal and high-normal blood pressure groups. The adjusted ORs for high-normal blood pressure group increased by 1.14, 95% CI 1.02–1.26 for every 300 m increase in the distance between the place of residence and city parks.Adjusting for age, education, socioeconomic position, passive smoking, BMI, chronic disease, parity, and stress did not substantially change the odds ratios, showing statistically significant results for the normal and high-normal blood pressure categories  for normal blood pressure and for high-normal blood pressure were statistically significant higher after the inclusion of the selected covariates in the categorical multinomial regression models. The analysis of continuous variables also showed an increase in the risk for normal blood pressure group by 9% and for high-normal blood pressure group ‒ by 14% for every 300 m increase in the distance from green spaces. However, the association between proximity to city parks and the hypertension group was not statistically significant.To address the question regarding if and how much green space as an independent factor contributes to blood pressure differences during first trimester of pregnancy, we used data from the well-characterised study of pregnant women of the city of Kaunas. Women during the first trimester of pregnancy are a suitable group for the study of hypertensive disorders, since even though changes in pregnancy lead to an increased stress on the cardiovascular system, such effects mainly occur from the second trimester of pregnancy on . TherefoIn this study, the impact of residential proximity to city parks on the doctor-diagnosed increased blood pressure were estimated by multinomial regression models with adjustments for age, education, body mass index, passive smoking, chronic diseases, alcohol consumption, and parity. We observed an impact on blood pressure even when the distance to a city park was included simultaneously in the model together with other individual covariates. The estimated impact showed an exposure-response pattern. Our results may show random variation; however, distance estimation on the individual level, control for the subjects’ migration effect, a strict protocol for measuring blood pressure, and control for possible confounding suggest that green space might contribute to blood pressure differences as an independent factor. This study is the first to investigate the association between residential proximity to city parks and the risk of increased blood pressure among pregnant women.Previous epidemiological research has found direct relationship between the blood level and the occurrence of cardiovascular events . A numbeOther publicised data showed that the availability of recreational spaces—such as parks—is associated with better perceived overall health , higher Our results are in accordance with other studies in which no statistically significant association was observed between access to parks and the prevalence of obesity or overweight ,40, or sTo our knowledge, only few published studies investigated the association between green environment and blood pressure using objective environmental characteristics . The autStudy findings from the Netherlands showed that neighbourhood-level environmental stressors were associated with blood pressure in ethnic minority groups, but the association was less evident in the Dutch group . The autStrength of the present population-based study is that we individually estimated green space exposure to the participants with the same ethnic culture and the health care system. Additional strengths include the possibility to control for potential confounding factors and the covariates of hypertension. Misclassifications of increased blood pressure cases were not likely, as physician-diagnosed blood pressure is generally considered to be reliable. Therefore, this study provides valid data for assessing the associations between proximity to city parks and blood pressure. We assigned increased blood pressure cases independently of environmental exposure; however, non-differential classification errors may have tended to underestimate the effects of the distance to green spaces , and thePreviously published data showed  that comIn conclusion, the findings of the present study extend the knowledge base with objective measures of the effect of green spaces on blood pressure elevation, and have an important public health application in supporting green urban planning policy, prioritising health, and preventing hypertension. Our results suggest that proximity to green spaces may positively affect women’s blood pressure. This association seemed to be independent of other known risk factors of hypertension. Further studies are required to explore the effects of the magnitude of green space exposure-response modifying factors (such as genetic susceptibility) on the course of hypertension, physical activity, use of recreational greenery and to explore the underlying mechanisms.


Prehypertension has been shown to be an early risk factor of cardiovascular disease (CVD). We investigated the prevalence and pattern of cardiometabolic risk factors in prehypertension in three ethnic Asian populations in Singapore.1c), body mass index (BMI), triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were examined as indicators of adverse cardiometabolic profile. The association between metabolic variables and prehypertension was examined using logistic regression models adjusting for potential confounders.We examined data from Chinese (n = 1177), Malay (n = 774), and Indian (n = 985) adults aged 40–80 years who participated in three independent population based studies conducted from 2004–2011 in Singapore who were free of diabetes, hypertension and previous CVD. Prehypertension was defined as systolic blood pressure (BP) 120–139 mm Hg or diastolic BP 80–89 mm Hg. Random blood glucose, glycated haemoglobin  of prehypertension in Chinese, Malays and Indians were: 1.42 , 1.53 , 1.49  for high-glucose; 3.50 , 3.72 , 2.79  for high-HbA1c; 1.86 , 2.96 , 1.68  for high-BMI. In addition, higher levels of LDL cholesterol in Chinese and higher levels of triglycerides were significantly associated with prehypertension. These associations persisted when metabolic variables were analysed as continuous variables.The prevalence of prehypertension was 59.8% (Chinese), 68.9%  and 57.7% Indians. Higher levels of blood glucose, HbA1c and BMI were associated with prehypertension in all three ethnic groups in Singapore. Screening for prehypertension and lifestyle modifications could potentially reduce the burden of CVD in otherwise healthy Asian adults living in Singapore.Higher levels of blood glucose, HbA Hypertension  is an imTo date no study has examined the association of cardiometabolic risk factors with prehypertension in Asia. This information is important because the prevalence of CVD is high among Asians and the contribution of major risk factors to CVD ,9 and diSingapore has a diverse ethnic population of Chinese, Malay and Indians and therefore ideally placed to study the ‘Asian’ cardiometabolic risk profiles and its association with prehypertension. In the current study, we examined the association between cardiometabolic risk factors and prehypertension in an apparently healthy multi-ethnic Singaporeans without diabetes mellitus, hypertension and preexisting CVD. Additionally, we examined the association of non-metabolic variables including demographic, lifestyle and socioeconomic factors with prehypertension. Examining the contribution of both cardiometabolic and non-cardiometabolic factors to prehypertension in different ethnic groups may better inform about the pathogenesis of prehypertension and intervention programs aimed at preventing and stemming the progression of cardiac or metabolic illnesses.We used data from three cross-sectional population based studies conducted in Singapore from 2004–2011: These studies include the Singapore Malay Eye (SIMES) Study  , hypertension n = 4124) and pre-existing CVD (n = 87), missing information on variables included in the multivariable analysis (n = 36), leaving 2936 for the final analysis . Questionnaires on demographic, lifestyle, personal and medical history were administered by trained interviewers. Physical examination by trained personnel included measurement of blood pressure and anthropometry. Information on random blood glucose, HbA4 and pre samples . WrittenSystolic and diastolic blood pressures were measured by trained clinic research assistants using a digital automatic blood pressure monitor , after the subject was seated for at least 5 minutes. Blood pressure was measured twice, 5 minutes apart. A third measurement was made if the systolic blood pressure differed by more than 10 mmHg or the diastolic by more than 5 mmHg. The mean between the two closest readings was then taken as the blood pressure for that individual. The blood pressure monitor was regularly calibrated by trained clinic staff. Participants with history of diabetes, CVD, and hypertension (includes those on hypertensive medication(s)) at the time of the study were excluded from the statistical analysis. Prehypertension was defined as systolic blood pressure (BP) ranging from 120–139 mm Hg and/or diastolic BP ranging from 80–89 mm Hg (definition used by JNC7) .1c), high-density lipoprotein (HDL), triglycerides, low density lipoprotein (LDL) and body mass index (BMI), as components of the metabolic syndrome. We defined the components of the metabolic syndrome categorically as 1. High-blood glucose, defined as blood glucose ≥ 5.5 mmol/L; 2. High-HbA1c as hbA1c > 6.5%; 3. Low-HDL cholesterol as HDL cholesterol < 1.0 in men and <1.3 mmol/L in women; 4. High-triglycerides as triglycerides ≥ 1.7 mmol/L; 5. High-LDL cholesterol ≥ 2.6 mmol/L; and 6. High-BMI as BMI ≥ 25.0 kg/m2. The above cut-off points were chosen based on the clinical cut points for adverse outcomes defined by the World Health Organization (WHO) and ATP-III [We examined blood glucose, glycated haemoglobin .All statistical analyses were performed using STATA version 12.0 . Characteristics of the study population were examined using proportions, or means, and standard deviation (SD) as appropriate for the variables. Metabolic variables were analysed both as categorical and continuous (per SD increase) variables. We examined the association of metabolic variables with prehypertension in two logistic regression models: model 1 adjusted for age and sex and model 2 adjusted additionally for income, education status, smoking, and alcohol consumption. We then examined the association of non-metabolic categorical variables with prehypertension in the same regression models. We performed the analysis separately for each ethnic group. Finally, in a separate analysis, we combined all three ethnic groups and in the whole population, we tested for interaction between metabolic variables and ethnicity by including cross-product interaction terms in the corresponding multivariable logistic regression models.Overall characteristics of the study population without hypertension, diabetes, and self-reported CVD by ethnic groups are shown in Table 1c.The age-adjusted prevalence of prehypertension was 63.7% in Chinese, 42.4% in Malays and 61.4% in Indians. Within each ethnic group . In analyses examining metabolic variables as continuous variables . Therefore, we do not believe that the main study results would be different if they were conducted in the same period . Finally1c and BMI were significantly associated with prehypertension in all three ethnic groups. Our findings suggest that prehypertension could serve as an early marker of adverse cardiometabolic profile in apparently healthy Asian adults and early detection and control of prehypertension could potentially reduce the burden of CVD in this Asian population.In conclusion, in a study involving apparently healthy Chinese, Malay and Indian adults free of diabetes, hypertension and CVD, we found that higher levels of blood glucose, HbAThe authors declare that they have no competing interests.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/730/prepub


In the past two decades, the international health efforts have been focused on the control of infectious diseases in developing countries with noncommunicable diseases (NCDs) given a lower priority. However,CKD is now a common health problem globally; up to 10% of world’s population is estimated to suffer from CKD. Number oIn 2004, over 700,000 patients were estimated to have CKD in Iran with incidence rate of 173.5/100,000. CKD was responsible for 1,145,654 disability adjusted life years (DALYs). Among the underlying causes for stages of 1 to 4 of CKD in Iranian population, DM and hypertension were the most common ones. In 2008, more than 24,000 patients were estimated to suffer from ESRD (stage 5 of CKD) in Iran. Patients with ESRD constitute the tip of iceberg of patients with varying degrees of CKD. By c By c10] Dipstick urine examination at least for high risk groups and shared care program are cost-effective for CKD screening and prevention. The costReducing the rate of hypertension, DM and its attendant cardiovascular disease will involve lifestyle modifications like weight reduction and a healthy diet including decrement in the consumption of saturated fat and synthetic foods and increment in consumption of fruits and vegetables, regular exercise, and cessation of smoking. DecreasiIn patients with CKD, target blood pressure (BP) levels should be < 130/80 mmHg and a tighter BP control (<125/75 mmHg) is recommended in patients with DM or proteinuria > 1 gram/ 24 hours.  AngiotenTraining of nephrologists and sustained education of general physicians and other health care personnel is an essential part of development of preventive measures for CKD. Furthermore, sustained collaboration among governmental agencies, health policy makers, pharmaceutical industry, international societies and philanthropic bodies is necessary. On March 10, 2011, the sixth World Kidney Day will be celebrated. This annual event has been initiated by International Society of Nephrology and International Federation of Kidney Foundations in order to raise the awareness of health care providers, government health officials and general public about kidney diseases and their attendant complications. World Kidney Day activities will provide a very good opportunity to appreciate and robust the notion that kidney disease is common, preventable and treatable. The theme of this year’s world kidney day is “Protect your kidneys and Save your heart”. CKD is aIn summary, CKD and its underlying diseases are becoming a major health problem in developing countries. Screening for the risk factors of CKD and their proper management has a great role in prevention of CKD in children and adults. This demands collaboration between health policy makers and governmental agencies, educated healthcare staff, sufficient financial support and extensive public education.


We investigated the effect of perindopril on pulse-wave velocity  and endothelin-1 (ET-1) levels in black hypertensive patients.Forty-four newly diagnosed hypertensive patients who received 4 mg perindopril daily were monitored for nine months. Pulse-wave velocity (PWV) was measured non-invasively along the carotid–femoral arterial segment (high elastic content) and the brachial–ulnar segment (low elastic content).There was a significant increase in arterial elasticity, as indicated by a slower PWV in the carotid–femoral segment of the treatment group, from 11.6 to 7.5 m/s after nine months. The PWV of the treatment group (7.5 m/s) after nine months was lower than that of the healthy volunteer group (8.2 m/s) but it was not statistically significant. No correlation between ET-1 and PWV could be found.In addition to its blood pressure-lowering effect, our study confirmed the improvement in arterial elasticity in patients on perindopril therapy, without involvement of ET-1. Pulse-wave velocity (PWV) has become the standard for measuring arterial elasticity or stiffness.4Decreased arterial elasticity and endothelial dysfunction are associated with end-organ damage and, together with pulse pressure, are independent predictors of cardiovascular risk in hypertensive patients.8Only a few studies, however, have reported the effect of different drug therapies on abnormal arterial elasticity. The methods differed widely and the patient numbers varied between 10 and 20.11In patients with congestive heart failure it has been shown that captopril decreased endothelin production.13In this study we investigated the effect of a nine-month treatment of the angiotensin converting enzyme inhibitor (ACEI) perindopril on arterial elasticity, brachial pulse pressure and the role of ET-1 in black hypertensive patients.Newly diagnosed hypertensive patients with a diastolic pressure of > 85 mmHg and/or a systolic pressure of > 135 mmHg were enrolled in the study. Only treatment-naïve patients were admitted into the trial, after informed consent was obtained.Patients with secondary hypertension or any concomitant disease were excluded from the study. Those who needed any treatment other than 4 mg of perindopril to control their hypertension were excluded. Patients who were on any chronic or acute medication were also excluded.Forty-four patients received 4 mg of perindopril daily for a period of nine months. Fifty-one healthy volunteers served as a reference group.PWV was used as a surrogate indicator of arterial elasticity and was measured non-invasively using a Powerlab 4 SP system  and connected to a desktop computer. PWV was measured along two segments of the arterial tree, the carotid–femoral segment  and the brachial–ulnar segment .t) between the recorded proximal (carotid) and distal  beginning of the upstroke of the wave, and the distance (∆d) separating the two respective transducers, according to the equation:The carotid–femoral PWV was calculated from the time delay (∆v) = ∆d∆tspeed  equipment . Other parameters and measurements included pulse pressure, body mass index (BMI) and lead II of an ECG.125I immuno-assay radioactive ligand system . Briefly, the assay is based on the competition between unlabelled ET-1 and a fixed quantity of 125I-labelled ET-3 (synthetic) for a limited number of binding sites on an ET-1-specific antibody. With fixed amounts of antibody and radioactive ligand, the amount of radioactive ligand bound by the antibody is inversely proportional to the concentration of the added non-radioactive ligand.Endothelin-1 was measured using an The antibody-bound ET-1 is then reacted with a second antibody that is bound to magnetisable polymer particles. Separation of the antibody-bound fraction is effected by centrifugation of the suspension and decantation of the supernatant. Measurement of the radioactivity in the pellet enables the amount of labelled ET-3 in the bound fraction to be calculated. The concentration of the unlabelled ET-1 in the sample was determined from a standard curve. All samples were done in triplicate.g for 10 minutes at 4°C to remove the cells, after which the plasma was stored at –70°C for later analysis. Samples were then prepared and analysed according to the manufacturer’s instructions.Venous blood (5 ml) was collected into heparinised tubes and centrifuged immediately at 2 000 × Blood was also collected for routine blood analysis, including renin, aldosterone, cholesterol, glucose and electrolyte levels, and liver function. In the hypertensive patients all measurements were done and blood samples collected at baseline (before therapy), and after one, three, six and nine months of therapy.p-value of < 0.05 was considered significant. Pearson’s coefficient was used to determine correlations between PWV, ET-1 levels and the other parameters. Descriptive statistics were given as median (1st quartile–3rd quartile).Analysis of variance (applying the Bonferroni principle) was used to determine intra-group variations at the different intervals. Comparisons between the control  and the experimental group (treatment-naïve patients) were done using the Mann-Whitney rank sum test. A The study was approved by the Medunsa Research Ethics Committee of the University of Limpopo, IRB 00005122.2 for the control group and 31.5 ± 6.9 kg/m2 for the patient group.Of the 44 newly diagnosed hypertensive patients, 14 were male and 30 female, aged 50.4 ± 7.6 years, whereas in the control group, 19 were male and 32 female, aged 43.2 ± 8.3 years. The BMI at the beginning of the study period was 28 ± 6.9 kg/mFive patients were regarded as lost to follow up, of whom three did not respond to perindopril alone and were give 2.5 mg indapamide, and three patients developed a dry cough. Thirty-nine patients completed the nine-month period on 4 mg perindopril.There was a significant decrease in systolic, diastolic and mean arterial pressure in the treatment group at each visit compared to baseline, but pulse pressure did not change. Values never reached the same level as those of the control group There was a significant continuous reduction in PWV that could indicate an increase in arterial elasticity in the carotid–femoral segment of the treatment group, from a median of 11.6 to 7.5 m/s over the nine-month period. The PWV of the treatment group (median 7.5 m/s) after nine months was lower than that of the healthy volunteer group (median 8.2 m/s) but was not statistically significant Although the absolute values of the PWV in the brachial–ulnar segment of the treatment group decreased over time, it was not significant. After the nine-month treatment, the average value was lower than that of the healthy volunteer group. The median PWV in the brachial–ulnar segment at all treatment intervals was lower than that of the carotid–femoral segment All values are given as median (1st–3rd quartile). ET-1 levels in the treatment group first increased from 6.15 (3.5–7.89) pmol/l at baseline to reach a maximum of 8.15 (5.32–9.63) pmol/l after six months but it was not significant. They then decreased to 4.53 (3.68–9.2) pmol/l after nine months.The ET-1 levels of the treatment group after nine months were lower than those of the healthy volunteer group but it was not significant. The baseline level of ET-1 in the treatment group was significantly higher [6.15 (3.5–7.89) pmol/l] than that of the healthy volunteer group [4.69 (3.0–5.4) pmol/l] Neither BMI nor other routine blood tests changed during the nine-month study period.In this study we investigated the effect of a nine-month treatment with the ACE inhibitor perindopril on PWV and the role of ET-1 in black hypertensive patients. PWV was used as a surrogate to indicate arterial elasticity, which includes structure, elastin and collagen.It has been shown that β-adrenergic blocking agents, diuretics, and some direct vasodilators such as hydralazine and dihydralazine, only lowered blood pressure but had no effect on vascular elasticity, whereas the ACE inhibitors, calcium channel blockers in general and nitroprusside, in addition to their blood pressure-lowering properties, also improved arterial elasticity.11In a number of studies, possible mechanisms were investigated. It was suggested that vascular collagen metabolism plays a role. However, no correlation could be found between matrix metalloproteinase (MMP)-1, the tissue inhibitor of MMP-1 (TIMMP-1), PWV and blood pressure in patients who received perindopril for six months.12However, in our study, no correlation could be found between ET-1 levels and arterial elasticity in any arterial segment or at any of the measured intervals. This was in contrast to a study done in endurance-trained men, where a linear correlation between ET-1 and aortic PWV was found.16The segment in which the arterial elasticity is measured is important. In a previous study it was found that perindopril had a smaller effect on the elasticity in the carotid artery than the femoral artery.18In addition to its blood pressure-lowering effect, our study confirms the improvement in arterial elasticity in the carotid–femoral segment but not the brachial–ulnar segment in patients on perindopril therapy. Furthermore, we have shown that ET-1 was not correlated to arterial elasticity in patients receiving perindopril.et al., the European Society of Hypertension has now included in their guidelines the improvement of arterial elasticity as one of the therapeutic aims in the treatment of hypertension.19As referenced by Milan


Sirs:The underlying mechanisms for the rise in blood pressure in individuals with autosomal dominant polycystic kidney disease (ADPKD) are complex, and experimental and clinical data support the concept that sympathetic hyperactivity may contribute to the pathogenesis of hypertension in ADPKD , 2.More recently, a catheter-based percutaneous aimed at ablating both efferent and afferent renal nerve fibres has been introduced into clinical medicine and has been demonstrated to safely and effectively reduce blood pressure in patients with treatment resistant hypertension and normal renal function –6. HowevA 26-year-old male with polycystic kidney disease was referred to the Department of Hypertension by the end of 2012 for the consideration of percutaneous renal denervation due to resistant hypertension. At the age of 20, the patient was first diagnosed with hypertension and also with ADPKD. A family history of polycystic kidney disease was present in the mother and in addition to in a sister.2. The patient was not troubled by chronic flank pain.At the time of referral, the patient had an office blood pressure of 162/77 mmHg and an average day-time ambulatory blood pressure of 138/73 mmHg despite four antihypertensive medications comprising valsartan 160 mg od, amlodipine 10 mg od, nebivolol 2.5 mg od, and hydrochlorothiazide 25 mg od. No history of cardiovascular disease or diabetes was reported, the patient has never smoked. The patient has normal renal function at baseline with a serum creatinine of 74 μmol/L and estimated glomerular filtration rate by MDRD formula of >60 mL/min/1.73 mOn Doppler duplex examination renal arteries were normal, renal resistive index values were 0.61 and 0.66 in the right and left kidney, respectively. Abdominal ultrasound showed enlarged size of right (145 mm) and left (180 mm) kidney with multiple simple renal cortical cysts with a maximum diameter of 3 cm. Hepatic cysts were not present. Abdominal MRI showed bilateral simple appearing renal cysts in the upper and lower poles.Microneurography was performed before and 3 months after the renal denervation. Muscle sympathetic-nerve activity (MSNA) signals were recorded by an electrode placed into the peroneal nerve at the popliteal fossa, posterior to the fibular head and the reference electrode was placed subcutaneously 2–3 cm from the recording electrode.® system was performed as described previously [Due to his uncontrollable blood pressure percutaneous renal sympathetic denervation using the Symplicity Cathetereviously , with fiThe patient was reviewed at 1 and 3 months post renal sympathetic denervation. At 1 month follow up he had improvement in his systolic blood pressure with an office reading of 129/60 mmHg and at 3 month follow up his blood pressure had dropped to 120/74 mmHg. A 24-h ambulatory blood pressure monitoring at 1 and 3 months confirmed blood pressure control with a mean day-time blood pressure of 131/68  and 128/65 mmHg, respectively. His renal function remained unchanged at 1 and 3 months. Microneurography at 3 months showed a reduction in MSNA (Fig. Our case report confirms the safety and effectiveness of a catheter-based renal denervation approach for the treatment of resistant hypertension in patients with ADPKD. While a single case has its obvious limitations, the fall in blood pressure after the procedure was accompanied by the decrease in the sympathetic activity being likely mediated via ablations of different fibres responsible. However, it should be mentioned that MSNA may not give information specifically about renal sympathetic activity .In our case, larger reductions in office than in ambulatory blood pressure were noticed. However, these changes were of comparable magnitude as reported in the prospective studies , 9, 10. Confirmation of substantial BP lowering via catheter-based renal afferent denervation in patients with ADPKD in future studies may provide a valuable and safe alternative for the management of this difficult clinical condition.


We aimed at reviewing age-related changes in kidney structure and function, methods for estimating kidney function, and impact of reduced kidney function on geriatric outcomes, as well as the reliability and applicability of equations for estimating glomerular filtration rate (eGFR) in older patients. CKD is associated with different comorbidities and adverse outcomes such as disability and premature death in older populations. Creatinine clearance and other methods for estimating kidney function are not easy to apply in older subjects. Thus, an accurate and reliable method for calculating eGFR would be highly desirable for early detection and management of CKD in this vulnerable population. Equations based on serum creatinine, age, race, and gender have been widely used. However, these equations have their own limitations, and no equation seems better than the other ones in older people. New equations specifically developed for use in older populations, especially those based on serum cystatin C, hold promises. However, further studies are needed to definitely accept them as the reference method to estimate kidney function in older patients in the clinical setting. Conversely, individuals with a GFR from 60 to 89 mL/min/1.73 m2 without kidney damage are classified as “decreased GFR.” In UK, the prevalence of CKD stages 3–5 (GFR < 60 mL/min/1.73 m2) is estimated to be 8.5%, and based on a review of 26 studies, a prevalence of CKD of 7.2% in patients aged >30 years and of 8% in patients aged >64 years was reported [Chronic kidney disease (CKD) is an important epidemic and public health problem, resulting in end-stage renal disease (ESRD) and increased risk of morbidity and mortality . Hence, In USA, the prevalence of CKD based on data from the third NHANES (NHANES III) was 11% . In this study, a graded increase in the prevalence of CKD was shown at older age groups . In a re125I-iothlamate, 51Cr-EDTA, or iohexol, are used to determine GFR. In the oldest subjects, the above mentioned techniques are not easily applicable and a 24-hour urine collection for creatinine clearance is often impracticable [The association between age and incident CKD was investigated among community-dwelling participants who were part of the Framingham Offspring Study (mean age at baseline: 43 years). For every 10-year increase in age, the odds ratio for developing incident CKD was 2.56 . CKD is cticable . For theThe aging process determines important modifications of kidney structure and function, such as kidney vasculature, filtration, and tubule-interstitial function . OverallSuch morphological changes determine important functional alterations and make the aging kidney more vulnerable to the development of kidney disease . Indeed,Aging kidney progressively loses its ability to maintain sodium/potassium balance due to the reduced tubular sodium secretion and potassium absorption . Sodium  per se seems to play a minor role in endocrine kidney functions.The kidney also plays an important role in synthesis, metabolism, and elimination of different hormones. While CKD naturally progresses with hormonal disorders , the agiKidneys are the primary sources of erythropoietin (EPO). Peritubular fibroblasts in the renal cortex are the main site of EPO synthesis, which is controlled by hypoxia-inducible transcription factors (HIFs) . EPO is α-hydroxylase to form the metabolically active form of vitamin D, 1,25-dihydroxvitamin D  . Parathyroid hormone (PTH) increases activity of the renal 1α-hydroxylase in response to low calcium levels. Age per se does not affect PTH and active vitamin D levels, which are usually normal in healthy older people [Vitamin D is necessary to maintain calcium homeostasis and optimal bone health . The mair people , whereasr people .A progressive reduction in renal function is linked to alterations in thyroid hormone levels and/or metabolism, resulting in high prevalence of subclinical hypothyroidism and the low T3 syndrome . This syKidney is the major site of insulin clearance from the systemic circulation, removing approximately 50% of insulin in the peripheral circulation. Insulin clearance by the kidney is accomplished by glomerular filtration and proximal tubular uptake and degradation . The ageFinally, alterations of sex steroid production and metabolism  are observed when moderate GFR reductions arise. As many as 40 to 60% of CKD stage-5 men have been reported to be hypogonadal on the basis of low concentrations of total and free testosterone .Measurement of renal function is important in the diagnosis and management of renal diseases. GFR is the standard measure of renal function. GFR is the rate at which substances are filtered from the blood of the glomeruli into Bowman's capsules of the nephrons. Any substance freely filtered by the glomerulus and not subsequently secreted, reabsorbed, or metabolized by the distal parts of the renal system has a clearance equivalent to the GFR. It correlates with renal damage in the kidneys of patients with chronic kidney disease, and it therefore reflects overall renal functional capacity. In addition, most functions of the kidney, including endocrine ones , are directly related to GFR. In addition, appropriate dosing of drugs excreted by the kidney depends on accurate estimation of GFR. For these reasons, GFR is the most widely accepted measurement for assessing the overall function of the kidney .Conventional techniques for estimating GFR use the principle of renal clearance of various markers of GFR, including creatinine, cystatin C, inulin, and radiocontrast agents . Renal clearance techniques involve measuring blood and urine concentrations of either endogenous  or exogenous  substances and calculating GFR from the ratio of urine to plasma concentrations of the marker, multiplied by the urine flow rate. These methods however are not always easily suitable in clinical practice. For this reason, equations for estimating GFR  were developed. In this section, we will discuss feasibility and reliability of these methods, with special attention to eGFR equations in older people.Inulin is an inert polyfructose sugar that does not bind to plasma protein, is freely filtered by the kidney, does not undergo metabolism, tubular secretion, or absorption, and is therefore rapidly excreted into the urine by glomerular filtration only. Measuring inulin clearance needs an indwelling intravenous cannula, and urinary catheter must be in place. The technique involves oral water loading (15–20 mL/kg) and intravenous loading dose of inulin of 30 to 50 mg/kg followed by a continuous infusion until establishing a steady-state plasma concentration of 15 to 20 mg/dL. The bladder is usually flushed with air to eliminate any pooled urine. After a 1 h equilibration period, three to four 30-min urine collections with midpoint (or flanking) blood specimens are obtained for measurement of blood and urine concentration of inulin . Clearan125I-Iothalamate has been widely adopted for measurement of GFR. To block thyroidal uptake, cold iodine is administered at the time of 125I-iothalamate administration, thus precluding its use in people with known allergies to iodine [Iothalamate is commonly administered as a radioactive iodine label for ease of assay after small doses; it is most commonly administered using bolus subcutaneous injection . 125I-Ioo iodine .In order to avoid the use of radioactive compounds, techniques have been developed aimed at detecting low levels of iodine compounds in the urine. This has allowed the use of nonradiolabeled iodinated contrast agents, such as iohexol. The assay of these agents can be obtained by high performance liquid chromatography (HPLC) , which i51Cr-EDTA consistently underestimates inulin clearance, probably because of tubular reabsorption [99mTc, may undergo extrarenal elimination and can bind to plasma proteins to a nonpredictable extent, leading to imprecision and bias [Among other markers, sorption . Diethetand bias .Measurement of the clearance of endogenous filtration markers, such as creatinine, is widely used in clinical setting.Creatinine is a metabolic product of creatine and phosphocreatine arising from the muscle compartment. Thus creatinine is directly related to muscle mass and undergoes little daily change . HoweverCurrent recommendation for creatinine measurement suggests the use of a standardized method based on modified Jaffé reaction, able to separate creatinine from noncreatinine chromogens , 52. UnfTo obtain creatinine clearance, a long urinary collection period—6 to 24 h—is used to avoid the requirement for water loading and, in the steady state, a single blood sample obtained either at the beginning or the end of the collection period may be assumed to represent the average serum concentration during the urine collection. Timed collections are subject to errors in older patients, due to inaccurate record of time and incomplete urine collection in patients with incontinence . The tubCystatin C (CysC) is a single chain basic protein with low molecular weight (13 kD) produced by all nucleated human cells, whose circulating concentrations can be easily determined by an automated particle-enhanced immunoturbidimetric method . CysC isEquations have been proposed in order to provide the physician an easy way of calculation and an accurate estimation of kidney function . The Coc125I-iothalamate clearance and were normalized to 1.73 m2 body surface area (BSA) [The Modification of Diet in Renal Disease Study (MDRD) equations were derived on the basis of measured ea (BSA) . Their uea (BSA) . Additioea (BSA) . Neverthea (BSA) . Indeed ea (BSA) .2 and more accurate than the MDRD equation at higher GFR values [CYS) or in combination with creatinine (CKD-EPICR-CYS) have been developed. Overall, the CKD-EPICR-CYS equation had better precision and accuracy than that based on creatinine alone or CysC alone [The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were developed in an attempt to improve the estimation of GFR in patients older than 70 years . CreatinR values , 79. To sC alone . NeverthCR-CYS and BIS2 equations showed better accuracy compared to MDRD, CKD-EPI, and BIS1 estimates.Recently, two eGFR equations were developed and validated in a population of older adults aged 70 years or more enrolled in the Berlin Initiative Study (BIS): the BIS1 equation based on serum creatinine alone and the BIS2 equation based on both serum creatinine and cystatin C . BIS equAlthough the overall prevalence of CKD is roughly 10% in the general population, it increases with age . AdditioSeveral studies have demonstrated that a reduction of eGFR is associated with lower scores in subjective physical function and physical activity scales . In an e2 compared to the general population [Osteoporosis and CKD are both common conditions in older adults and may be associated with substantial morbidity . In the pulation . Additiopulation . DisordeCognitive impairment has been frequently observed in patients with CKD especially in older subjects . CKD is Stroke is the most frequent neurological disease and represents a continuously evolving medical and social problem . A TaiwaDepression is frequently observed in elderly patients with CKD . This isAnemia is commonly related to CKD, and it is typically normocytic, normochromic, and hypoproliferative . In prosObstructive sleep apnea (OSA) is an important and common comorbidity in patients with CKD . OSA incChronic obstructive pulmonary disease (COPD) dramatically increases with age and it is a progressive, debilitating respiratory condition . COPD isCachexia is an important cause of death in elderly CKD patients, even if it is not completely clear whether malnutrition is part of a cause-effect relationship. In adult CKD patients, decreased appetite plays a major role in wasting. Wasting has also been linked to high levels of leptin and proinflammatory cytokines . MalnutrWhen renal function declines, many drugs or their active metabolites that depend on renal excretion may accumulate with an increase of potential toxicity, and patients with renal disease may be more vulnerable to a given drug effect . This neDespite the huge amount of findings described above, eGFR has some important limitations when applied to older and frail patients. Indeed, whatever is the equation used to estimate GFR, the interpretation of results obtained in older people may not be so easy.2 enrolled in the Hull and East Yorkshire renal and diabetes registers [2 or more enrolled in the HYVET trial [2 in the large population study of the Alberta Kidney Disease Network repository [An example of how it can be difficult to understand the meaning of these measures in frail and older patients comes from studies showing the existence of a U-shaped relationship between eGFR and mortality. By using MDRD equation, Cox et al. showed for the first time that all-cause mortality risk increased in subjects with eGFR higher than 89 mL/min/1.73 megisters . An incrET trial . All-caupository . Finallypository . There apository : (i) a dpository , 125 (hopository ); (ii) apository ; (iii) hpository . Interespository . Thus, dpository , CysC-baAnother potential issue is represented by the difference among kidney function estimates obtained with different equations. Structural differences between equations likely account for discrepancy. Indeed, the Cockcroft-Gault equation intends to measure the creatinine clearance, whereas all other equations listed in The prevalence of CKD increases with age, and CKD is often associated with several comorbid conditions and adverse outcomes in older patients. Thus, the availability of an accurate method for estimating kidney function in this highly vulnerable population would be of paramount importance.Methods based on clearance of radiolabelled or nonradiolabelled exogenous markers are expensive and not easy to apply in clinical settings. Kidney function estimate based on simple determination of serum creatinine level is hardly reliable in older patients because of the frequent loss of muscle mass secondary to age itself and aging-related conditions. Additionally, the clearance of creatinine is often biased in older patients due to inaccurate or incomplete urine collection. GFR equations may facilitate the estimation of kidney function in older patients. However, all of them have their own limitations, and no equation proved to be better than the other ones. New equations specifically developed for use in older people, especially those based on serum cystatin C, hold promises. However, few studies have been carried out to definitely accept them as the reference method to estimate kidney function in older patients in clinical practice. Further research is needed to verify whether these new equations can overcome the above described issues in prognostic stratification and dosing of kidney cleared drugs.


Genetic variants of Y chromosome predispose to hypertension in rodents, whereas in humans the evidence is conflicting. Our purpose was to study the distribution of a panel of Y chromosome markers in a cohort from a cross-sectional population-based study on the prevalence of cardiovascular risk factors in Poland (WOBASZ study). The HindIII, YAP Y chromosome variants, previously shown to influence blood pressure, lipid traits or height, as well as SNPs defining main Y chromosome haplogroups, were typed in 3026, 2783 and 2652 samples, respectively. In addition, 4 subgroups (N∼100 each) representing extremes of LDL concentration or blood pressure (BP) were typed for a panel of 17 STRs. The HindIII and YAP polymorphism were not associated with any of the studied traits. Analysis of the haplogroup distribution showed an association between higher HDL level and hg I-M170 (P = 0.02), higher LDL level and hg F* (P = 0.03) and lower BMI and hg N3-Tat (P = 0.04). Analysis of STRs did not show statistically significant differences. Since all these associations lost statistical significance after Bonferroni correction, we conclude that a major role of Y chromosome genetic variation  in determining cardiovascular risk in Poles is unlikely. Genetic variants of Y chromosome have been shown to predispose to hypertension in a series of rodent experiments Despite the abovementioned reports, the association between Y chromosome HindIII polymorphism and hypertension or lipid profile remains controversial as it was not observed in recent relatively large studies encompassing Caucasians from the UK Whereas analysis of candidate markers chosen on the basis of proven or likely functional significance represent a direct way to study the role of Y chromosome variation in predisposing to disease(s), the problem may also be approached by taking advantage of growing knowledge of the evolutionary history of this part of the genome. Since the major part of Y chromosome does not recombine during meiosis, all newly arising variants remain in virtually absolute linkage disequilibrium with variants present in the chromosome in which the mutation has occurred In order to resolve the described controversies we set out to study the distribution of Y chromosome genetic markers in a large sample of Polish males, comprehensively characterized with respect to cardiovascular risk factors and ascertained independently from previously studied cohorts We studied males from the WOBASZ study, which is a cross-sectional population-based study aimed at delineation of classical and genetic risk factors for cardiovascular diseases as described previously All participants gave two consents in writing: one for evaluation of conventional cardiovascular risk factors and one for taking a blood sample for DNA isolation and genetic tests. Questionnaire data were collected by certified pollsters who were also responsible for ascertaining that all subjects had full capacity/ability to participate in the study as well as to give their informed consent. The study was approved by The Medical Ethics Committee of the National Institute of Cardiology in Warsaw.2. Blood pressure measurements were taken thrice on the right arm after 5 minutes of rest in a sitting position in one minute intervals. The value used in analyses was the average of the 2nd and 3rd measurement. Hypertension was defined as systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or use of antihypertensive medication.The height and weight of each patient were measured and the body mass index (BMI) was calculated according to the formula: BMI = weight (kg)/height (m)Two blood samples obtained after 8–12 h of fasting were used for DNA isolation and for biochemistry tests, respectively. The blood samples for DNA extraction were stored at −70°C until the DNA was isolated by a salting out-method. Biochemical tests  were performed at the Central Laboratory of the National Institute of Cardiology in Warsaw. Total cholesterol, LDL-cholesterol, HDL-cholesterol and glucose concentration were estimated using the Roche INTEGRA 400 Analyzer with Roche reagents. Concentration of triglycerides (TG) was determined by the enzymatic-colorimetric method (GPO/PAP/kit), with glycerophosphate and 4-amidoantypiryn. Glucose concentration was estimated using the enzymatic reference method with hexokinase.In males typed for HindIII from whom a sufficient amount of DNA was available, we also performed an analysis of YAP variants and Y chromosome haplogroups. The call rate was >0.95% and the results were obtained for following numbers of samples: N = 3026 (HindIII), N = 2 783 (YAP) and N = 2 652 (Y chr. haplogroups). Furthermore, we performed an analysis of STR markers in four groups of ∼100 samples representing extreme phenotypes for blood pressure and LDL concentration, which are likely to be enriched for genetic variants influencing these traits. The groups were selected from those genotyped for HindIII polymorphism according to following criteria: group 1 (H_BP) – presence of hypertension, age below 35 years, group 2 (L_BP) – normal blood pressure, age over 55 years, group 3 (H_LDL) – LDL concentration above 4 mmol/l, age below 40 years, group 4 (L_LDL) – LDL concentration below 3 mmol/l, age over 55 years. The call rate in STR analysis ranged from >0.92%–98% .Genotyping for HindIII polymorphism was performed by PCR-RFLP as described previously Haplogroup typing was based on a phylogenetic tree published by YCC Applied Biosystems, Foster City, CA). After the SNaPshot reaction samples were run on a Genetic Analyzer 3130 (Applied Biosystems) and the data were analyzed by GeneScan Analysis software (Applied Biosystems). Analysis of chromatograms for each triplex allowed to assign samples to haplogroups: R1a1-M17, R1*(xR1a1-M17), J2-M172, N3-Tat, I-M170 and E3b-M35. Samples with no mutated allele in any of the tested loci were additionally typed for M74 and M89 markers. PCR amplification of the M74 marker was performed according to data shown in Fermentas, Vilnus, Lithuania) at 37°C for 3 hours. RsaI digestion yields fragments of sizes 104 and 47 bp when the segment contains allele M74A and 151 bp when the probe contains ancestral allel M74G. Typing for M89 marker was performed according to Ke et al. Y-Filer kit from Applied Biosystems, according to the manufacturer's instructions. DYS385 1 and DYS385 2 were not analyzed due to the fact that these loci are amplified by one set of Y-filer primers and thus cannot be reliably distinguished Samples typed as M9G were subsequently genotyped by SNaPshot technique for the M17, M173 and Tat (M46) markers, whereas samples typed as M9C for the M170, M172 and M35 markers. PCR amplification of these markers was performed in two triplex reactions. Primers were designed according to guidelines of Juan and Sanchez Statistica or SPSS software packages. In the analysis of the Y chromosome haplogroups, Bonferroni correction was applied with correction factor of 7 .For continuous variables, differences between groups were analyzed with student t test. Calculations were performed with Our study had the following power to detect effects of HindIII polymorphism, as previously reported in a Polish population Distribution of the studied parameters according to Y chromosome HindIII and YAP markers is shown in In When comparing distribution of alleles of 19 Y chromosome STRs in groups with high and low LDL concentration , and high and low blood pressure  we found no statistically significant differences  we also determined distribution of SNPs allowing to assign major Y chromosome haplogroups. Whereas these SNPs probably do not have any functional significance, they define phylogenetically distinct Y chromosome pools and at least some of them would be expected to be in linkage disequilibrium with the putative variant(s) influencing cardiovascular risk sought in this study. Although we observed three associations significant at alpha = 0.05 we think they are unlikely to be genuine for two reasons: (i) none withstood Bonferroni correction despite the modest correction factor applied (n = 7), (ii) they did not point to a single haplogroup as harboring risk variant(s). Analysis of Y chromosome STRs in subgroups likely to represent the extremes of distribution of the genetic burden for high LDL concentration or high BP did not show any associations, further strengthening the conclusions from HindIII, YAP and haplogroups analyses.In conclusion, our study shows that in humans Y chromosome genetic polymorphism, in particular the widely studied HindIII variant, does not influence blood pressure, lipid traits or anthropometric measures, such as height, weight or waist/hips circum ference.File S1Comparison of distribution of alleles of studied Y-STR loci in groups with high and low LDL concentration  and high and low blood pressure . P values calculated by permutation based Fisher exact test . The ‘Total’ refers to samples in which result was obtained . Table S1, Comparison of distribution of DYS456 in groups with high and low LDL concentration. Table S2, Comparison of distribution of DYS389I in groups with high and low LDL concentration. Table S3, Comparison of distribution of DYS390 in groups with high and low LDL concentration. Table S4, Comparison of distribution of DYS389II in groups with high and low LDL concentration. Table S5, Comparison of distribution of DYS19 in groups with high and low LDL concentration. Table S6, Comparison of distribution of DYS391 in groups with high and low LDL concentration. Table S7, Comparison of distribution of DYS439 in groups with high and low LDL concentration. Table S8, Comparison of distribution of DYS635 in groups with high and low LDL concentration. Table S9, Comparison of distribution of DYS392 in groups with high and low LDL concentration. Table S10, Comparison of distribution of GATAH4 in groups with high and low LDL concentration. Table S11, Comparison of distribution of DYS437 in groups with high and low LDL concentration. Table S12, Comparison of distribution of DYS448 in groups with high and low LDL concentration. Table S13, Comparison of distribution of DYS456 in groups with high and low blood pressure. Table S14, Comparison of distribution of DYS389I in groups with high and low blood pressure. Table S15, Comparison of distribution of DYS389II in groups with high and low blood pressure. Table S16, Comparison of distribution of DYS19 in groups with high and low blood pressure. Table S17, Comparison of distribution of DYS385I in groups with high and low blood pressure. Table S18, Comparison of distribution of DYS391 in groups with high and low blood pressure. Table S19, Comparison of distribution of DYS439 in groups with high and low blood pressure. Table S20, Comparison of distribution of DYS635 in groups with high and low blood pressure. Table S21, Comparison of distribution of GATAH4 in groups with high and low blood pressure. Table S22, Comparison of distribution of DYS437 in groups with high and low blood pressure. Table S23, Comparison of distribution of DYS438 in groups with high and low blood pressure. Table S24, Comparison of distribution of DYS448 in groups with high and low blood pressure.(DOC)Click here for additional data file.


Establishment of the health impact of hypertension on quality of life of Nigerians is a step towards controlling the disease. The study aimed to provide a Nigerian specific reference list of utility scores of hypertensive patients with various interacting conditions.An interviewer-based, cross-sectional study was conducted using hypertensive patients in two purposively selected tertiary hospitals located in South-Eastern Nigeria. Health Utility Index Mark 3 (HUI3) was used.A total of 384 participants with either hypertension alone or with hypertension-associated complications were interviewed in the two tertiary hospitals.The overall mean utility score was 0.35 +/- 0.42. Patients with hypertension alone had the highest overall mean utility score (0.57 +/- 0.29) while hypertensive patients with stroke had the lowest overall mean score (0.04 +/- 0.36). Being a male, increase in age and mean arterial blood pressure, emergency visit and loss of work due to illness were associated with significant decrease in overall utility scores.This study presented a reference for health state utilities of a population of Nigerian hypertensive patients. Hypertension is a major cardiovascular risk factor. Direct correlations between blood pressure (BP) values and risk of cardiovascular diseases (CVDs) have been established based principally on epidemiologic data. Beginning at a benchmark BP of 115/75 mmHg, the risk of CVD doubles with every increment of 20/10 mmHg [There is growing evidence that prevalence of hypertension is on the increase in most sub-Saharan African countries including Nigeria . The curEstablishing the health impact of hypertension on quality of life of Nigerians is a step towards checking the disease. This will highlight the need to address the emerging burden. For this, utility measures are often employed. Economic evaluation of programmes to detect and treat hypertension by improving awareness, treatment and adherence and level of control has been identified as a research priority in hypertension for developing nations such as Nigeria  and utilThe aim of this study is to provide a Nigerian specific reference list of utility scores of hypertensive patients with various interacting cardiovascular conditions. A catalogue of utilities scores of Nigerian hypertensive patients would enable more efficient economic analyses of health interventions.A descriptive study was conducted to assess a cross-section of hypertensive patients with or without hypertension-associated complications  in two pThe HUI3 was used to measure the health state utilities of the patients. This measure is a preference-based health related quality of life instrument that use multi-attributable utility theory to assign valuations to different health states . Health ® . A two-tailed significance level of 0.05 was used.To assess predictors of HUI scores, overall utility score served as the dependent variable while some selected patient's demographic and clinical variables served as independent variables. Study variables found to be correlated to overall utility scores after adjusting for confounding variables were used in a multiple linear regression. Stepwise method was used to model the effect of predictor variables on overall utility scores. Analysis of impact of cardiovascular comordities on overall utility scores of the patients was conducted using ANOVA (LSD for multiple comparisons). Data analysis was conducted with SPSS 11.0All procedures were carried out according to a study protocol approved by the Local Ethics Committee of University of Nigeria Teaching Hospital Enugu (UNTH/CSA.329.Vol.6) and Ebonyi State University Teaching Hospital (EBSUTH/CMAC/RM/VOL1/046/48). Oral informed consent was obtained. The information about participant's identity was not included with the other data and only the principal investigator had access to this information. No reference to the participant's identity was made at any stage during data analysisA total of 635 patients were approached for interview while only 384 participants (60.5%) with either hypertension alone or hypertension-associated complication participated in the study. Lack of time or interest was the major reason given by those that did not participate. Each interview took an average of 6 minutes +/- 1 minute. Majority of the participants were from University of Nigeria Teaching Hospital and the ratio of male to female was almost equal. A small number of the participants had no formal education. Other clinical variables of the participants are shown in Table In Table p < 0.001, showing that the results were unlikely to have arisen by sampling error.In Table Health state utilities of Nigerian hypertensive patients were assessed in this study employing a standard and widely used quality of life measure, the Health Utilities Index Mark 3 . AlthougIn this study, variables such as being a male as well as increase in age and mean arterial blood pressure, emergency visit to the hospital and loss of work due to illness were all associated with decrease in overall utility scores. Apart from sex  all the variables found to lower overall utility scores are expected to cause decrement in health related quality of life. It is important to state that the findings from most quality of life studies show the contrary (i.e. women have lower utilities compared to men) ,18. ThisAs established in this study, cardiovascular comorbidities were associated with lower utility scores. Specifically, stroke did not have any negative impact on hearing although it did affect vision. This finding is somewhat in agreement with another study which found that stroke and arthritis did not affect speech and cognition . CoronarThis study had some limitations which should be taken into consideration when interpreting the results. The cross-sectional nature of the study and the convenience sampling may affect the generalizability of the study. Secondly, the study made use of a small sample size as a result language barrier which precluded those that could not understand and speak English language.This assessment presents a reference for health state utilities of hypertensive patients with or without associated complications. The utility scores could facilitate health economic evaluations conducted to provide evidence for decision making in health care.The authors declare that they have no competing interests.OIE and CNA designed the study. OIE, EB and CJO actively implemented the study. MOA carried out the statistical analysis. All the authors were involved in articles write-up. All authors read and approved the final manuscript.


About 39,000 patients were newly prescribed renal replacement therapy in Japan in 2011, resulting in a total of more than 300,000 patients being treated with dialysis. This high prevalence of treated end stage kidney disease (ESKD) patients is an emergent problem that requires immediate attention. We launched a prospective cohort study to evaluate population specific characteristics of the progression of chronic kidney disease (CKD). In this report, we describe the baseline characteristics and risk factors for cardiovascular disease (CVD) prevalence among this cohort.New patients from 16 nephrology centers who were older than 20 years of age and who visited or were referred for the treatment of CKD stage 2–5, but were not on dialysis therapy, were recruited in this study. At enrollment, medical history, lifestyle behaviors, functional status and current medications were recorded, and blood and urine samples were collected. Estimated glomerular filtration rate (eGFR) was calculated by a modified three-variable equation.We enrolled 1138 patients, 69.6% of whom were male, with a mean age of 68 years. Compared with Western cohorts, patients in this study had a lower body mass index (BMI) and higher proteinuria. The prevalence of CVD was 26.8%, which was lower than that in Western cohorts but higher than that in the general Japanese population. Multivariate analysis demonstrated the following association with CVD prevalence: hypertension (adjusted odds ratio (aOR) 3.57; 95% confidence interval (CI) 1.82-7.02); diabetes ; hemoglobin level less than 11 g/dl ; receiving anti-hypertensive agents ; and statin therapy . The combination of decreased eGFR and increased proteinuria was also associated with a higher prevalence of CVD.The participants in this cohort had a lower BMI, higher proteinuria and lower prevalence of CVD compared with Western cohorts. Lower eGFR and high proteinuria were associated with CVD prevalence. Prospective follow up of these study patients will contribute to establishment of individual population-based treatment of CKD. Chronic kidney disease (CKD) is a major global health problem. In Japan, about 13% of the adult population, i.e. approximately 13.3 million people, are estimated to have CKD . The incCKD is also a well-known risk factor for cardiovascular mortality and morbidity -6. ReporWe established a large prospective cohort study of Japanese people with CKD called the CKD-ROUTE study (CKD Research of Outcomes in Treatment and Epidemiology). The specific aim of the CKD-ROUTE study is to evaluate the relationship of CKD progression, cardiovascular events and mortality to patient characteristics, complications and treatment. The findings of this study will contribute to development of appropriate therapy for CKD in the Japanese population, whose characteristics are quite different from Western populations. The study is presently ongoing, although enrollment of patients has been completed. In this report, we address whether the basic characteristics and risk factors related to CVD prevalence in Japanese patients are different from those in other ethnic groups.The CKD-ROUTE study is a prospective, observational cohort of a representative Japanese population with CKD stages 2–5 who are not on dialysis. Over 1000 participants were enrolled at the Tokyo Medical and Dental University Hospital and its 15 affiliated, larger than mid-sized clinical centers located in the Tokyo metropolitan area of Japan, where one third of the Japanese population lives. Most patients were referred from primary care clinics. At recruitment, written informed consent was obtained from all patients and their eligibility was determined. Approval for this study was obtained from the ethics committees of all institutions participating in the study (see Acknowledgments), and the research is being conducted in accordance with the ethical principles of the Declaration of Helsinki. The protocol was registered in UMIN Clinical Trials Registry (UMIN000004461).Participants were eligible for inclusion if they: (1) newly visited or were newly referred to the participant nephrology centers from October 2010 to December 2011; (2) were over 20 years of age; and (3) had CKD stages 2 to 5 according to Kidney Disease Improving Global Outcomes (KDIGO) classification . Stage 5The primary study outcome is decline in renal function, defined by reduction in eGFR. Secondary outcomes are incidence of CV events, initiation of dialysis, death, hospitalization, bone fractures, and changes in the levels of blood and urine biochemical measurements, blood pressure, bodyweight and body mass index (BMI).One of the major endpoints of the CKD-ROUTE study is initiation of dialysis. If the event rate of initiation of dialysis is presumed to be about 30% according to the rates shown in previous studies ,14, in t− 1.094 × age− 0.287  [At enrollment, medical history, lifestyle behaviors (self-feeding ability) and current medications were recorded. Anthropometric measurements (height and weight) were obtained and BMI was calculated. Blood pressure (BP) was measured using a standard sphygmomanometer. Blood and urine samples were collected to measure white blood cell, hemoglobin (Hb), platelet, total protein, albumin, urea nitrogen, creatinine, sodium, potassium, chloride, calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone (PTH), glucose, hemoglobin A1c (HbA1c), iron, unsaturated iron binding capacity, ferritin, C-reactive protein, urinary occult blood, urinary protein, and urinary creatinine. Estimated glomerular filtration rate (eGFR) was calculated using the modified three-variable Modification of Diet in Renal Disease (MDRD) equation developed by the Japanese Society of Nephrology to adjust for Japanese physical characteristics: eGFR = 194 × serum creatinine× 0.739) . Since t× 0.739) . Correct× 0.739) . All par× 0.739) ,17.Hypertension at entry was defined as systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, use of anti-hypertensive agents, or history of being diagnosed with hypertension. Diabetes was defined as either HbA1c ≥ 6.5%  method) or receiving anti-diabetic therapy. Etiology of kidney disease in each patient was determined by the physician who was treating the patient at the time of enrollment, based on patients’ past histories, clinical characteristics and findings, and histological findings in biopsied kidney specimens.CVD was defined as a history of coronary heart disease (angina pectoris (AP), myocardial infarction (MI), or coronary revascularization), congestive heart failure (CHF), peripheral arterial disease (PAD) , or stroke . Prevalence of CVD at enrollment represented a composite of self-reported history of CVD or information provided by previous doctors.Baseline characteristics are shown as mean ± standard deviation and median with interquartile ranges for continuous variables, while categorical data are presented as numbers and percentages. Analysis of variance and chi-square test were used to compare continuous and categorical variables across CKD stages, respectively. Multivariate logistic regression analysis was used to identify the relationship between the composite CVD prevalence and predictor variables.P-value <0.05 was considered statistically significant.Statistical analyses were performed using SPSS, version 20.0. After excluding those who matched the exclusion criteria, we enrolled 1138 patients in this cohort from October 2010 to December 2011. Although we did not accurately count the number of those who were excluded in this registry, we speculate that a less than 5% of the new CKD stage 2–5 patients were excluded due to the exclusion criteria.2, while 32.8% of them were overweight (BMI ≥ 25 kg/m2). 37.1% of the patients were diabetic. Although the percentage of patients with diabetes was significantly higher in advanced CKD stages, HbA1c was not significantly different among CKD stages. Regarding the causes of CKD, the incidence of diabetic nephropathy was higher in advanced CKD stages, while nephrosclerosis and glomerulonephritis were more frequent in moderate CKD stages. Nephrosclerosis was the overall leading cause of CKD in this cohort, through CKD stage 2–5. CVD was prevalent in 26.8% of all the patients, and patients with advanced CKD were more likely to have CVD, the prevalence being 35.7% in stage 4 and 30.6% in stage 5 patients. Regarding the individual causes of CVD, the incidence of AP, MI, PAD and stroke were highest in stage 4 patients, the incidence of CHF gradually increasing with CKD progression  was present in 35.6% of the patients, the incidence being higher in advanced CKD stages. Iron deficiency (transferrin saturation (TSAT) < 20% and ferritin < 100 ng/ml) was seen in 14.9% patients, its incidence being highest in stage 4 patients. The percentage of patients receiving oral iron supplementation and erythropoiesis stimulating agents (ESA) increased in advanced CKD groups.A trend existed between decreasing eGFR and the increasing percentage of patients with low HDL-cholesterol. The percentage of patients with high LDL-cholesterol was higher in stage 2 and stayed relatively low through stages 3 to 5. Statin therapy was prescribed in 28.6% of patients, the percentage significantly increasing in advanced CKD groups.Low corrected serum calcium levels (< 8.4 mg/dl) and high phosphorus levels (≥ 4.6 mg/dl) were seen in patients with stage 5 CKD. The percentage of patients with high intact PTH levels (> 65 pg/ml) was 15.9% in stage 2, 32.2% in stage 3, 68% in stage 4 and 95.5% in stage 5 CKD, respectively. On urinalysis, UPCR was significantly higher in advanced CKD stages, with 90% of stage 5 CKD patients having a UPCR over 0.5 g/gCr.The results of multiple logistic regression analysis of the risk factors that predict the prevalence of CVD at enrollment are shown in Table Figure The CKD-ROUTE study was established to identify the risk factors of CKD and effects of treatment on its progression. A unique characteristics of this study is that all enrolled patients are those who newly visited or were referred to our nephrology centers. This gives us information on the basic characteristics of the patients before they receive specific treatment from nephrologists, allowing clear evaluation of the efficacy of the treatment by nephrologists in a prospective manner. Although the dietary habits in Japan have been westernized, there are many differences between Japanese compared to Western populations, such as lower calorie intake, smaller body size and lower BMI ,19. It iKeeping such differences in mind, at the completion of the enrollment, we addressed whether the basic characteristics of ROUTE patients are different from those of Western cohorts, such as those in the CRIC study in the US ,21, CRISAlthough the prevalence of CVD in ROUTE participants is lower than that in Western CKD cohorts Table , it is sAs expected, hypertension and diabetes were associated with CVD prevalence. Although receiving anti-hypertensive therapy was an associated factor for CVD, SBP ≥ 130 mmHg at enrollment was not a significant predictor. This could be explained by the fact that patients with CVD were already prescribed anti-hypertensive drugs by primary care physicians, resulting in normalized BP. Interestingly, the adjusted odds ratio for the use of diuretics was higher than for other anti-hypertensive agents. A most likely explanation for this would be that participants with CVD have been prescribed diuretics for treatment of CHF or edema. Although not shown, the fact that 78.7% of the patients who experienced CHF used diuretics supports this explanation.Increasing UPCR was also associated with the prevalence of CVD. Furthermore, as shown in Figure Dyslipidemia is a conventional CV risk factor that is also commonly observed in CKD patients, with an increasing incidence with progression of CKD stage . Statins2 are much more likely to have anemia, and the prevalence and severity of anemia increases with declining kidney function [Anemia was also an associated factor of CVD prevalence in this study. Patients with eGFR below 60 ml/min per 1.73 mfunction . In the The ROUTE participants were characterized by low BMI, high proteinuria and low prevalence of CVD. Hypertension, diabetes, anemia, decreasing eGFR and increasing proteinuria are associated with the prevalence of CVD. Receiving anti-hypertensive agents, statin therapy and treatment for anemia are also associated with the prevalence of CVD. Prospective follow up of ROUTE participants treated by nephrologists will provide high quality evidence of the risk factors of progression of CKD and their appropriate treatment.ESKD: End stage kidney disease; CKD: Chronic kidney disease; CVD: Cardiovascular disease; eGFR: Estimated glomerular filtration rate; BMI: Body mass index; aOR: Adjusted odds ratio; NHANES: National health and nutrition examination surveys; CV: Cardiovascular; ROUTE: Research and outcome in treatment and epidemiology; NKF: National kidney foundation; K/DOQI: Kidney disease outcomes quality initiative; BP: Blood pressure; MDRD: Modification of diet in renal disease; Ca: Calcium; UPCR: Urinary protein to creatinine ratio; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; HbA1c: Hemoglobin A1c; NGSP: National glycohemoglobin standardization program; AP: Angina pectoris; MI: Myocardial infarction; CHF: Congestive heart failure; PAD: Peripheral arterial disease; Hb: Hemoglobin; TSAT: Transferrin saturation; ESA: Erythropoiesis stimulation agent; PTH: Parathyroid hormone.The authors declare that they have no competing interests.YN and SN contributed to the design of this study. SI managed the database, performed statistical analysis and drafted the manuscript. SS contributed to organizing the study and writing the manuscript. EK advised on statistical analysis. SI, YN, TO, SN, TT, YC, MK, RA, YN, YM, HT, TT, SK, EK, SI, MY, RO, MT, TK, KK, TR, SU and SS treated the patients and provided the patients’ data. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/14/152/prepubRisk factors for the presence of cardiovascular disease excluding congestive heart failure, CKD-ROUTE study (Oct 2010 - Dec 2011).Click here for file