Hypertension is a major challenge to public health as it is frequently associated with sudden death due to the silent nature of the condition. By the time of diagnosis, some patients would have developed target-organ damage (TOD) and associated clinical conditions (ACC) due to low levels of detection, treatment and control. TOD and ACC are easy to evaluate in a primary healthcare (PHC) setting and offer valuable information for stratifying cardiovascular risks in the patient. The aim of this study was to evaluate the prevalence and correlates of TOD and established cardiovascular disease (CVD) in hypertensive Nigerian adults.A cross-sectional study was conducted on 2 000 healthy Yoruba adults between 18 and 64 years who lived in a rural community in south-western Nigeria. Participants diagnosed to have hypertension were examined for TOD and ACC by the presence of electrocardiographically determined left ventricular hypertrophy (LVH), microalbuminuria or proteinuria, retinopathy, or history of myocardial infarction and stroke.A total of 415 hypertensive participants were examined and of these, 179 (43.1%) had evidence of TOD and 45 (10.8%) had established CVD. TOD was associated with significantly higher systolic (SBP) and diastolic blood pressure (DBP). The prevalence of LVH was 27.9%, atrial fibrillation 16.4%, microalbuminuria 12.3%, proteinuria 15.2%, hypertensive retinopathy 2.2%, stroke 6.3%, congestive heart failure (CHF) 4.6%, ischaemic heart disease 1.7%, and peripheral vascular disease 3.6%. Compared with those with normal blood pressure (BP), the multivariate adjusted odds ratios  of developing TOD was 3.61 (0.59–8.73) for those with newly diagnosed hypertension; 4.76 (1.30–13.06) for those with BP ≥ 180/110 mmHg; and 1.85 (0.74–8.59) for those with diabetes mellitus.This study provides new data on TOD and its correlates in a nationally representative sample of hypertensive adults in Nigeria. In this low-resource setting, attempts should be made to detect hypertensive patients early within the community and manage them appropriately before irreversible organ damage and complications set in. The methods used in this study are simple and adaptable at the primary healthcare level for planning prevention and intervention programmes. Hypertension is often asymptomatic and recording blood pressure is opportunistic. Many of these patients are unaware of their condition and therefore remain untreated. Untreated or poorly controlled hypertension and left ventricular hypertrophy (LVH) are risk factors for cardiovascular diseases (CVD),A number of hypertensives may present for the first time with target-organ damage (TOD) involving various organs. Therefore at initial diagnosis, they already have hypertensive heart disease (HHD); some with LVH, while some have frank congestive heart failure (CHF). CHF is a lethal disease with a poor prognosis and reduced life expectancy.Major TOD of hypertension such as LVH,11In Nigeria, little is known about the experiences of caregivers and care-seeking practices with regard to hypertension and factors influencing late presentation with TOD. Some of the undiagnosed hypertensives are detected incidentally during the course of management for other clinical conditions or during catastrophic events. The challenge to the physician therefore is early detection and treatment of hypertension before progression to complications of TOD, which portends a poor prognosis.There are few studies on target-organ involvement in hypertensive Nigerian patients at the secondary and tertiary level of care,This work was part of a community-based, descriptive, non-interventional, cross-sectional survey of cardiometabolic risk factors, conducted from December 2002 to November 2005 in the Egbeda local government area (ELGA), a rural community in south-western Nigeria, with a population of 128 000. The local governments are serviced by PHCs which are meant to serve as the initial point of care for the majority of patients in Nigeria. The study protocol was evaluated and approved by the Ethics of Human Research Committee of the State Ministry of Health. Individual consent was obtained verbally and where possible by written consent.Four hundred and fifteen confirmed hypertensive adults  above 18 years of age who participated in the cross-sectional, community-based survey formed the population for this study. Socio-demographic and anthropometric data were collected for each subject. Self-reported and patient clinical records of established CVD and complications such as heart failure, stroke, myocardial infarction, angina, peripheral vascular disease and kidney disease were recorded.Clinic blood pressure (BP) was measured by trained health workers in each PHC, according to guidelines of the International Society of Hypertension (ISH)/World Health Organisation (WHO) 1999 and the JNC-7.Participants with an elevated BP measurement were invited to attend a second clinic visit after one to two weeks to have their BP measured again. The average BP of the second visit was used as a criterion for the diagnosis and control of hypertension. In addition, all treated hypertensive patients were asked to return for a second visit after one to two weeks to have their BP measured.Hypertension was defined as systolic blood pressure (SBP) ≤ 140 mmHg, diastolic blood pressure (DBP) ≤ 90 mm Hg, or current treatment with antihypertensive drugs in subjects with a history of hypertension.2 + RV6 in males of ≥ 40 mm and females of ≥ 35 mm and RI ≥ 12 mm. These criteria have been shown to correlate better with echocardiograhic LVH in Nigerians.20Each subject underwent further physical examination to determine clinical features of LVH, CHF, stroke, renal failure, and fundoscopy for hypertensive retinopathy. Hypertensive cardiac damage was defined by the presence of electrocardiographic (ECG) LVH based on the voltage criteria of AraoyeRenal damage was diagnosed based on the presence of microalbuminuria as determined by spot urine albumin-to-creatinine ratio [ACR (mg/g)]. In males, ACR < 2.5 mg/g is normal, 2.5–25 mg/g defines microalbuminuria and > 25 mg/g indicates gross proteinuria. In females, ACR < 3.0 mg/g is normal, 3.0–30 mg/g defines microalbuminuria, and > 30 mg/g indicates gross proteinuria.24Venous blood samples were obtained via the ante-cubital vein for biochemical assessment, including fasting serum total cholesterol, high-density lipoprotein cholesterol (HDL-C) and fasting blood glucose levels.The data obtained were analysed using SPSS version 13.0 software . Descriptive analysis of the variables was performed to process the data as tables. Continuous variables were described by calculating the means and standard deviation (SD). Categorical variables were described using frequency tables.p < 0.001). SBP and DBP did not vary significantly according to gender. The detection and treatment rate of hypertension was low in the studied population. Only 14.2% of the subjects had self-reported hypertension and of these, only 18.6% had been on medications in the past three months; of whom only 27.3% had controlled blood pressure. This means that only 5.1% of subjects who had self-reported hypertension had controlled BP at the time of the study.A total of 415 subjects consisting of 184 men (44.3%) and 231 women (55.7%) participated in the study. The baseline characteristics of the subjects are shown in The antihypertensive drugs used either alone or in combination included centrally acting alpha-adrenergic agonists such as α-methyl DOPA and Brinerdin (74.3%), thiazide diuretics (86.1%), calcium channel blockers (15.6%) and ACE inhibitors (1.7%). Some of the subjects who self-reported hypertension were on benzodiazepines prescribed as antihypertensives by their general practitioner.The prevalence of diabetes among the participants was 9.6% (7.1% in men and 11.7% in women). The prevalence of smoking in the study population was 5.1% and all the cigarette smokers were men.p = 0.12). The blood pressure of subjects in relation to TOD is shown in p < 0.001) mean SBP (167.1 ± 15.6 mmHg) than those without TOD (156.3 ± 18.7 mmHg). Mean DBP was also significantly higher (p < 0.001) in those with TOD (102.3 ± 9.5 mmHg) than those without (95.8 ± 13.5 mmHg).p < 0.001) SBP (161.7 ± 18.9 mmHg) compared to those without LVH (153.3 ± 16.2 mmHg) and their DBP was also significantly higher (p < 0.001) at 99.4 ± 9.5 mmHg, compared with 91.5 ± 10.1 mmHg.The prevalence of LVH was 27.9% and atrial fibrillation was 16.4%. Subjects with LVH had significantly higher , followed by grade 2 (37.6%). Microalbuminuria was present in 12.3% and gross proteinuria in 15.2%. The established CVD found in the subjects is shown in The results of multiple regression analyses after adjusting for potentially confounding variables are presented in The main findings of this study were the following: (1) The presence of TOD was frequent in this rural adult population; (2) The peak age for incidence of TOD was around 47 to 50 years, that is middle age; (3) TOD was related to the presence of newly diagnosed hypertension, stage 3 SBP and DBP, and diabetes mellitus; (4) The presence of established CVD was relatively frequent in this population; (5) There was a low detection rate, treatment and control of hypertension; (6) Atrial fibrillation was found in 16.4% of the population and this may have increased the risk of stroke as no patients were on treatment; (7) In spite of the low levels of angina and myocardial infarction, ischaemic changes and evidence of old infarcts were found in the ECGs of 12.3% of the population studied.The present study contributes to our knowledge on TOD in Nigerian hypertensives in several ways. First, our study demonstrates an incidence rate of TOD of 43.1% and established CVD of 10.8% among a nationally representative sample of the adult population of hypertensive Nigerians. Most studies of this nature have been conducted in hypertensive Nigerian patients attending healthcare facilities.The relatively high prevalence of TOD among the community of rural-dwelling adults is worrisome as it approaches previously reported hospital-based values of 53.3%Some of the subjects had had their blood pressure measured for the first time during the study. Of those who had had previous blood pressure measurements, the definition of hypertension by their attending medical team was 160/95 mmHg. These physicians had failed to commence appropriate management even at this level. Furthermore, only 18.6% of the self-reported hypertensives were on any form of treatment, which was mostly suboptimal. Of these, only 27.3% had their blood pressure controlled. There is an urgent need for training and retraining of both the care givers and care seekers at the community and PHC levels in order to reduce the burden of CVD in the population.The prevalence of ECG-LVH was nearly 28%, based on Araoye’s criteria,28Left atrial enlargement (LAE) was present on the ECGs of 21.9% of the subjects and atrial fibrillation in 16.4%. These are known risk factors for thrombo-embolic strokes and in the presence of hypertension, they may worsen the prognosis. Hypertension, a major risk factor for stroke in sub-Saharan Africa, including Nigeria, has been reported to occur in 33 to 62% of those with cerebral infarction and 60 to 92% of those with cerebral haemorrhage.29The relatively high prevalence of stroke in our study population was 6.3% and this was comparable to a hospital-based report of 8.9%Kidney damage was found in 27.5% of the subjects and of these, 12.3% had microalbuminuria, while 15.2% had gross proteinuria. There is disparity between our findings and a previous study that reported microalbuminuria in 37% and overt proteinuria in 2% of newly diagnosed Nigerian hypertensives.16p < 0.001) higher SBP and DBP compared with subjects who had neither TOD. In a study on TOD in hypertensive Ghanaian civil servants,In our study, subjects who had ECG abnormalities and evidence of kidney damage had statistically significantly . Invariably, patients on such treatments will have uncontrolled BP and are likely to have more TOD and established CVD, with worse outcomes. Newly diagnosed hypertensives should have their cardiovascular risks fully assessed and appropriately managed. Since stage 3 hypertension was associated with significantly increased odds of developing TOD, efforts should be made to aggressively lower and control BP in such individuals.Our study had some limitations. The investigations did not include echocardiography for assessment of LVH, which is more sensitive than ECG. However, we used locally validated Araoye’s criteria to determine LVH with ECG, as this was likely to give us a more accurate diagnosis.This study showed a high level of TOD and established CVD in this rural population of hypertensives. Our findings strongly suggest that the epidemiological transition from communicable to non-communicable diseases is occurring at a faster rate than previously envisaged. In this low-resource setting, there is an urgent need for primordial and primary prevention of hypertension and its complications. Once detected, BP should be properly controlled with appropriate medications. To this effect, both the populace and health practitioners should receive health education and health promotion to reduce the burden of disease.


Aims. Aim of the study was to evaluate the effect of smoking on autonomic nervous system (ANS) activity and QTc interval duration in patients with Type 2 diabetes mellitus (T2DM). Methods. A total of 70 patients with T2DM  treated with oral antidiabetic medications underwent continuous ECG Holter monitoring for 24 hours and analysis of time- and frequency-domain measures of heart rate variability (HRV). HRV over short time was also assessed using the deep breathing test. In addition, baroreflex sensitivity (BRS) was evaluated using the spontaneous sequence method. The mean QTc interval was measured from the 24-hour ECG recordings. Results. Smokers had lower body mass index (BMI) and exhibited higher 24-hour mean heart rate. There was no difference regarding all measures of ANS activity between the two groups. Smokers showed increased mean QTc duration during the 24 hours  as well as in both day  and night periods . The association between smoking status and mean QTc interval persisted after adjusting for BMI. Conclusions. Cigarette smoking is associated with prolongation of the QTc interval in patients with T2DM by a mechanism independent of ANS dysfunction. Patients with Type 2 diabetes mellitus (T2DM) who smoke are at increased risk of developing cardiovascular disease, including cardiac arrhythmias . ProlongAutonomic nervous system (ANS) function has been consistently shown to be associated with QTc interval duration in patients with diabetes and in healthy individuals . FurtherIt is well known that cigarette smoking alters autonomic cardiac control  and arteThe aim of the present study was to evaluate QTc interval duration in smokers compared to nonsmokers with Type 2 diabetes mellitus, in relation to ANS activity.β-blockers, antiarrhythmic drugs, and medications known to affect ANS activity or increase QT interval duration. In addition, patients who had coronary heart disease, cardiac arrhythmias, or any history of other chronic disease were excluded from the study. All patients had normal thyroid function and serum electrolytes. Patients who reported any hypoglycaemic event during the 24 hours prior to the study were also excluded. Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or the use of antihypertensive medication. The study was approved by the participating Hospital's Ethics Committee and carried out in accordance with the principles of the Declaration of Helsinki, as revised in 2008 [A total of 35 consecutive chronic smokers with T2DM, matched one-to-one for age, sex, and duration of diabetes with 35 never-smokers with T2DM, were included in the study. To decide about the required sample size and since there is lack of relevant data in the literature, we, a priori, hypothesised that a QTc difference of 10 ± 5 ms between the two studied groups would be clinically significant and meaningful. Thus, and in order to achieve statistical power greater than or equal to 90%, at 5% Type I error rate of two sided hypotheses, a total of 35 consecutive chronic smokers with T2DM, matched one-to-one for age, sex, and duration of diabetes with 35 never-smokers with T2DM, was deemed adequate. Smoking status was expressed using the Brinkman index (BI), which was calculated by multiplying the number of cigarettes smoked per day by the duration of smoking in years . None of in 2008 . The patAll patients underwent continuous ECG Holter monitoring for 24 hours. For this study the digital ECG Holter recorder Spider View  with seven electrodes was used to record three-channel ECGs. The 24-hour recordings were analysed using the SyneScope Holter analysis software . Artefacts and ectopic beats were automatically edited from analysis. In addition, the QRS complex classification was reviewed by an experienced cardiologist blinded to the patients' clinical characteristics.2. Furthermore, the LF and HF powers were expressed in normalised units (nu). The LF and HF powers expressed in nu represent the relative value of each power component in proportion to the total power minus the VLF component [All the time- and frequency-domain parameters of HRV recommended by the Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology were calculated from the 24-hour ECG recordings . The valomponent .QT intervals were measured from the 24-hour ECG recordings using the semiautomated method and corrected for heart rate using Bazett's formula (QTc = QT/√RR) . The QTcAll measurements took place between 8:00 and 10:00 am in a quiet room, with stable temperature (20–24°C). Both tests were performed following an adequate rest period of 20 minutes. All patients were fasted for 8 hours and studied in the supine position.BRS estimation was carried out by the spontaneous sequence method using the BaroCor System . The BaroCor System enables the calculation of BRS from the estimated central blood pressure changes on heart rate using a radial artery tonometer . Central blood pressure values were estimated from radial measurements using the mathematical transfer function proposed by Chen et al. . ContinuHRV during deep breathing was evaluated in all patients using the VariaCardio TF4-System . The result provided by the software was assessed by calculating the ratio of the maximum and minimum heart rates during six cycles of paced deep breathing and expressed as the Expiration-Inspiration ratio (E/I ratio) .t-test, while nonparametric variables with the Wilcoxon Mann-Whitney U Test. Associations between categorical variables were tested with the use of contingency tables and the calculation of the Chi-square test. Multivariate linear regression analysis was performed to assess the possible combined influence of the different variables on QTc interval duration. All statistical tests were performed by using SPSS v18.0 .Continuous variables are presented as mean ± one-standard deviation. Normality of distributions was evaluated with the Kolmogorov-Smirnov test, and a significance level <0.05 was used to reject the null hypothesis of normal distribution. Nonnormally distributed variables were log-transformed for analysis. Comparisons between normally distributed continuous variables were performed with the calculation of the Student's 2, P = 0.026). In addition there was no difference between the two groups regarding the use of medications for treatment of T2DM, hypertension, and dyslipidaemia. As expected, smokers had significantly higher mean 24-hour heart rate , due to smoking-induced adrenergic stimulation.The demographic and clinical characteristics of the study participants are summarised in All values of HRV parameters are presented in detail in Tables P = 0.021), as well as in both day  and night periods  , as well as during the day  and night periods . However, there was no statistically significant correlation between mean QTc interval duration and the Brinkman index.Smokers showed increased mean QTc duration during the 24 hours  , Table 4P = 0.086) exhibited QTc values longer than 440 ms  versus 11/35 (31%) (P = 0.22) during the day and 19/35 (54%) versus 11/35 (31%) (P = 0.064) during the night periods). Furthermore, during the 24-hour period, 17/35 (48.5%) chronic smokers versus 10/35 (28.5%) nonsmokers  compared to never-smokers, suggesting impaired ANS activity in the former group. HRV indices  were not different between the two groups. The distinction however of the present study was that BRS was assessed by the phenylephrine method, and HRV analysis was performed on 5 min ECG recordings. In the present study, BRS was assessed by the spontaneous sequence method, and HRV was measured by 24-hour ECG recordings, which are considered as more reliable techniques [Although there are many reports suggesting that smoking reduces HRV and attenuates BRS in normal individuals , there ichniques . The assP = 0.086) to exhibit QTc > 440 ms and, respectively, during the day (P = 0.22) and the night periods (P = 0.064).There is evidence that, in patients with diabetes, QTc interval prolongation could be associated with an increased risk of unexpected death, while at the same time QTc has been shown to be an accurate predictor of cardiac death in newly diagnosed patients with T2DM . In the There is no widely accepted single approach to the evaluation of ANS function in diabetes. Many methods have been proposed , a multiStrength of the present study is the fact that ANS function was assessed by a multitude of methods  and thus could provide an accurate assessment of it. In addition, smokers were matched one-to-one to nonsmokers in terms of age, gender, and diabetes duration and thus could eliminate potential bias due to these confounding factors.Cigarette smoking, especially in combination with T2DM, is well known to increase the risk for accelerated atherosclerosis, which leads to coronary artery disease . EndotheFurthermore, it is very difficult to deduce that there is a cause and effect connection between QTc interval prolongation and smoking from the present data. Subclinical coronary heart disease, known to prolong QTc interval , cannot In conclusion, the present study showed that cigarette smoking was associated with prolongation of the QTc interval in patients with T2DM by a mechanism independent of ANS dysfunction, and this effect may be implicated with an increased cardiovascular risk in this population. Confirmation of the current findings in a larger prospective cohort study is definitely needed in order to validate these results and assess their generalizability in the general diabetic population.


Type 2 diabetes mellitus (T2DM) patients are at increased risk of developing cardiovascular events. Unfortunately traditional risk assessment scores, including the Framingham Risk Score (FRS), have only modest accuracy in cardiovascular risk prediction in these patients.We sought to determine the prognostic values of different non-invasive markers of atherosclerosis, including brachial artery endothelial function, carotid artery atheroma burden, ankle-brachial index, arterial stiffness and computed tomography coronary artery calcium score (CACS) in 151 T2DM Chinese patients that were identified low-intermediate risk from the FRS recalibrated for Chinese (<20% risk in 10 years). Patients were prospectively followed-up and presence of atherosclerotic events documented for a mean duration of 61 ± 16 months.P = 0.21). Among different vascular assessments, CACS > 40 had the best prognostic value  and offered significantly better accuracy in prediction compared with FRS (P = 0.038 for AUC comparisons). Combination of FRS with CACS or other surrogate vascular markers did not further improve the prognostic values over CACS alone. Multivariate Cox regression analysis identified CACS > 40 as an independent predictor of atherosclerotic events in T2DM patients .A total of 17 atherosclerotic events in 16 patients (11%) occurred during the follow-up period. The mean FRS of the study population was 5.0 ± 4.6% and area under curve (AUC) from receiver operating characteristic curve analysis for prediction of atherosclerotic events was 0.59 ± 0.07 (In T2DM patients identified as low-intermediate risk by the FRS, a raised CACS > 40 was an independent predictor for atherosclerotic events. Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing adverse atherosclerotic events including acute coronary syndrome (ACS) and ischemic stroke -3. VarioSurrogate markers of atherosclerosis, including brachial artery flow-mediated dilatation (FMD), carotid artery atheroma burden, ankle-brachial index (ABI), arterial stiffness and computed tomography coronary artery calcium score (CACS) have been increasingly used for the prediction of cardiovascular events -16. PrioConsecutive Chinese patients with T2DM as defined by the WHO criteria were prospectively recruited from the Medical Outpatient Clinics from July 2005 to December 2006 ,25. PatiBaseline demographic data, cardiovascular risk factors and cardiovascular medication at the time of recruitment were documented. Cardiovascular risk factors including tobacco smoking, hypercholesterolemia, hypertension and family history of CVD diagnosed in first-degree relatives before 55 years of age were assessed. Hypertension was defined as either resting systolic or diastolic blood pressure ≥140 or ≥90 mmHg respectively, recorded at two different clinical visits or the prescription of anti-hypertensive medication . Hyperch2. Systolic and diastolic blood pressures were measured and fasting blood samples were obtained to measure serum levels of glucose, hemoglobin A1c (HbA1c), total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and creatinine. Glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease Study equation [Anthropometric measurements including body weight, height and waist-hip circumference ratio (WHR) were performed. Body-mass index (BMI) was calculated as kg/mequation .Vascular ultrasound examination for brachial endothelial function, carotid IMT and presence of carotid plaque was evaluated through a standard B-mode ultrasound examination with the use of a 7.5 MHz linear array transducer and a high resolution ultrasound system  as described previously . MeasureA single experienced operator blinded to the status of the study subjects performed all vascular ultrasound examinations. Another experienced operator, also blinded to the status of study subjects, operated on VP-2000 and obtained ABI and arterial stiffness parameters.Patients were studied in the fasting state and vasoactive medications were withheld for 12 hours prior to the scans. Longitudinal brachial artery diameter was obtained at rest, and then during FMD, induced by inflation of a pneumatic tourniquet placed around the forearm to a pressure of 50 mmHg above systolic blood pressure for 5 minutes. The cuff was then released and serial imaging of the brachial artery was recorded for 5 minutes. FMD was defined as the percentage change in brachial artery diameter between 1 minute following cuff deflation and that on the baseline scan. All digital images were stored on optical diskettes for subsequent off-line analysis using a computer workstation . A single operator measured the brachial artery diameter and an average value from three consecutive measurements was calculated. The intra-observer correlation coefficient for FMD was 0.90 (2 repeated measurements in 20 randomly chosen subjects).Carotid IMT was determined by measuring manually the distance between the lumen-intima and media-adventia border of the vascular wall using electronic calipers. Each ultrasonic scan was performed in the anterior, lateral and posterior projections of the right and left carotid arteries. Three IMT measurements were made on the near and far wall of the common carotid arteries, carotid bifurcation and internal carotid arteries. The mean maximum IMT (mmIMT) was used for analysis and was calculated by averaging the values of maximum IMT from 12 pre-selected segments of the carotid arteries. Presence of carotid plaque was defined as an endoluminal protrusion of the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstration of an IMT of >1.5 mm . The intMeasurements of ABI and arterial stiffness were performed with subjects in the supine resting position in a quiet and temperature-controlled room. Pneumatic pressure cuffs with oscillometric pressure sensors were wrapped tightly around both arms and both ankles. Electrocardiographic electrodes were attached to both wrists and a phonocardiogram was placed at the left second intercostal space, at the margin of the sternum. After ensuring that patients had rested for 15 minutes, fully automatic data acquisition began. Pressure waveforms of the brachial and posterior tibial arteries were recorded. Based on the height of the patient, the device estimated the path lengths from the brachial artery to the posterior tibial artery. BaPWV was calculated as the path length divided by the corresponding time interval (cm/s). The right and left baPWV were averaged and the resulting value selected as the representative baPWV.The pneumatic cuffs over both arms and ankles enabled simultaneous measurement of systolic blood pressure at each limb. The right-and left-sided ABI were calculated as the ankle systolic blood pressure divided by the brachial systolic blood pressure measured from the right and left side, respectively. The right and left ABI were averaged and the resulting value selected as the representative ABI.The intra-observer correlation coefficient for ABI was 0.85 and the intra-observer correlation coefficient for baPWV was 0.98 (2 repeated measurements in 20 randomly chosen subjects).All subjects underwent computed tomography imaging of the coronary arteries using a 64 slice MDCT  as described previously ,31. All The acquired MDCT images were reviewed at the post-processing image workstation . Complete data were available from all scans, with no mis-registration of slices due to artifacts of motion, respiration, or asynchronous electrocardiographic triggering. To ensure continuity and consistency of interpretation of calcium scores, two expert investigators, who were unaware of subject’s clinical status, analyzed all scans. The inter-observer and intra-observer variability correlation coefficients of CACS measurements were 0.92 and 0.91, respectively.Measurement of CACS was performed using a commercially available software “smart score”  using the threshold option set for pixels >130 Hounsefiled units and expressed in Agaston units. CACS was calculated as the sum of calcium scores in the left main coronary artery, left anterior descending artery, left circumflex coronary artery, right coronary artery, and posterior descending artery.All patients were followed-up in our clinic every 3–4 months. Clinical data of all patients were retrieved from the medical records and subsequently during the most recent clinic visit. An adverse atherosclerotic event was defined as ACS, ischemic stroke, new onset symptomatic peripheral vascular disease, death due to ACS or ischemic stroke or symptom driven revascularization procedures of the carotid, coronary or peripheral arteries.Power calculation was performed based on the prediction values of coronary artery calcium score for atherosclerotic events in patients with type 2 diabetes. Using an alpha of 0.05 and total sample size of 151 would give a power of 80%.t-test or Chi-squared test, as appropriate. Pearson’s correlation was used to measure the correlations between vascular assessment variables. Area under receiver operating curves (AUC) were calculated and the cut-off values of the vascular assessments with optimal sensitivity and specificity were obtained. These cut-off values were then used in subsequent analysis to determine the prognostic role of these surrogate markers in the prediction of atherosclerotic events. Chi-squared test was also used to compare the predictive accuracy between FRS and vascular markers in atherosclerotic event prediction. The associations between vascular assessment parameters, categorized by AUC cut-off values, and event-free survival were evaluated using Cox regression models with adjustment for potential confounding variables. Only parameters with P < 0.1 in uni-variate analysis were entered into a multi-variate model to identify the independent predictors for atherosclerotic events. Cumulative event rates were estimated using the Kaplan-Meier method and compared using log-rank test.Data were expressed as mean ± standard deviation for continuous variables and proportions for categorical variables. Baseline characteristics were compared between groups using Student’s P value <0.05 was considered statistically significant.All statistical analyses were performed using the statistical software SPSS for Windows  and STATA for Windows . A 2. The mean FRS of the study population was 5.0 ± 4.6%. Results of the vascular assessment parameters are shown in Table Clinical characteristics of the study population are summarized in Table P < 0.01). CACS also correlated well with mmIMT, ABI and baPWV  and mmIMT correlated well with CACS, ABI and baPWV . FMD showed no correlation with the FRS nor with the other vascular markers.Table During a mean follow-up of 61 ± 16 months (range 3–75 months), 17 atherosclerotic events including 1 cardiovascular death, 1 ACS, three ischemic stroke, 2 new onset peripheral vascular disease and 11 percutaneous coronary interventions were observed in 16 patients (11% of the study population). Elective percutaneous coronary interventions were performed at a mean of 8 ± 4 months following CT examination. All percutaneous coronary interventions were performed for treatment of symptomatic coronary artery disease and / or based on the presence of inducible ischemia detected by functional assessment rather than the results of CACS.P = 0.047). There was also a trend for patients with atherosclerotic events to be older , have a lower BMI  and a lower GFR . There were nonetheless no significant differences between the two groups in terms of gender, proportions with hypertension or hypercholesterolemia, duration of DM, HbA1c or use of medication.Table P = 0.047) and CACS  than those without atherosclerotic events. No significant differences in FRS, brachial artery FMD, prevalence of carotid plaque, ABI or baPWV were observed between the two groups.Patients with atherosclerotic events had a significantly greater carotid artery mmIMT . In contrast, of all the vascular assessment parameters tested, CACS >40 had the best predictive power for an atherosclerotic event  followed by carotid artery mmIMT > 1.07 mm .ROC curves were constructed to obtain the prognostic values and optimal cut-off values of the FRS as well as different vascular assessment parameters Table . All of P < 0.1). Multi-variate Cox regression analysis revealed that mean ABI ≤0.98 (Hazards ratio (HR) 7.17, 95% CI  1.63-31.52, P = 0.009) and CACS >40  were independent predictors of an atherosclerotic event (Table P = 0.077). In Kaplan-Meier analysis, a raised CACS >40 was associated with the occurrence of an atherosclerotic event during follow-up . There were no significant differences in AUC between other vascular markers and FRS . Combining CACS with FRS provided incremental benefit in risk prediction compared with FRS alone  but did not offer further benefit compared with CACS alone. Combination of FRS with other vascular markers also did not provide further incremental benefit.Finally, we compared the predictive power of FRS for atherosclerotic events against other vascular assessment markers, alone and in combination with the FRS Table . CACS haThis study compared the diagnostic value of non-invasive markers of atherosclerosis, used alone and with the FRS, in the prediction of atherosclerotic events in Chinese T2DM deemed low-intermediate risk. The results of our study show that in Chinese T2DM patients of low-intermediate risk, 11% developed an atherosclerotic event during a mean follow-up of 61 ± 16 months. The FRS only had a modest accuracy in prediction of atherosclerotic events in our study. In contrast, among the different surrogate markers of atherosclerosis evaluated, a raised CACS > 40 offered the best prognostic value and was superior to FRS in risk prediction. It was also an independent predictor of a future atherosclerotic event. Although combination of CACS with FRS provided incremental benefit in risk prediction versus FRS alone, such a combination did not offer further prognostic value compared with CACS alone.The FRS has been successful in prediction of CVD in general populations. The risk algorithm nonetheless lacks accuracy in patients with diabetes ,5. StudiIn view of the FRS’s drawbacks, further strategies to improve risk stratification should be implemented. Previous studies have identified that use of non-invasive surrogate markers of atherosclerosis including brachial artery FMD, carotid atheroma burden, ABI, arterial stiffness and CACS improve CVD risk stratification in the general population ,15,17-22Amongst commonly used non-invasive surrogate markers of atherosclerosis, a raised CACS was determined to have the best prognostic value in this study with a high negative predictive value of 98.7%. This finding is consistent with similar studies that also showed CACS to be superior to other markers for CVD prediction in the general population ,34. It hThe most recent international guidelines provide clear recommendations for initiation of antiplatelet therapy in diabetic patients considered to be at high cardiovascular risk  and does not recommend such therapy for those at low risk (men <50 years or women <60 years with no major cardiovascular risk factors) . NonetheIn this prospective observational study, there was a small sample size that of only 151 Chinese patients with T2DM resulting in 17 events. Further large scale studies replicated in other ethnic populations and using other risk algorithms are needed to confirm our findings. In addition, there is increasing interest in coronary artery plaque location and morphology as detected by contrast CT coronary angiogram but this was not assessed in the current study ,37. FinaIn this small study, detection of CACS > 40 was an independent predictor for atherosclerotic events in T2DM patients identified as low-intermediate risk by the FRS.The author(s) declare that they have no competing interests.KKL carried out the study and wrote the manuscript; YKW retrieved the follow-up data & performed the statistical analysis; YHC, KHY & KCT recruited the subjects & performed the vascular assessments; LSWL, SLH, KHC & CWS supervised the study; and HFT supervised the study design as well as writing of the manuscript. All authors read and approved the final manuscript.


Additionally, we emphasize the putative contributions of gene-environment interactions, discuss the implications of these findings to treat and prevent hypertension and CKD. Finally, we conclude with a strategic agenda and vision required to accelerate advances in this under-studied field of renal pharmacogenomics with vast significance for global public health.Pharmacogenomics is a field with origins in the study of monogenic variations in drug metabolism in the 1950s. Perhaps because of these historical underpinnings, there has been an intensive investigation of 'hepatic pharmacogenes' such as CYP450s and liver drug metabolism using pharmacogenomics approaches over the past five decades. Surprisingly, kidney pathophysiology, attendant diseases and treatment outcomes have been vastly under-studied and under-theorized despite their central importance in maintenance of health, susceptibility to disease and rational personalized therapeutics. Indeed, chronic kidney disease (CKD) represents an increasing public health burden worldwide, both in developed and developing countries. Patients with CKD suffer from high cardiovascular morbidity and mortality, which is mainly attributable to cardiovascular events before reaching end-stage renal disease. In this paper, we focus our analyses on renal function before end-stage renal disease, as seen through the lens of pharmacogenomics and human genomic variation. We herein synthesize the recent evidence linking selected Very Important Pharmacogenes (VIP) to renal function, blood pressure and salt-sensitivity in humans, and ways in which these insights might inform rational personalized therapeutics. Notably, we highlight and present the rationale for three applications that we consider as important and actionable therapeutic and preventive focus areas in renal pharmacogenomics: 1) ACE inhibitors, as a  In the latter study [ACE DD genotype was associated with higher risk of stroke (OR[95%CI]=1.91 1.56-2.34). In a meta-analysis involving 1121 patients with preeclampsia and 1361 controls from 11 studies =1.24 [1.12-1.37]) ) . This wa2-1.37]) . When st2-1.37]) . The ACEhropathy .ACE I/D polymorphism in non-diabetic renal disease is less well established [ACE I/D polymorphism was not associated with renal function [ACE locus did not come out from large scale genome-wide meta-analyses of renal function or CKD [ACE I/D polymorphism was not associated with ESRD or risk of hypertension in patients with autosomal dominant polycystic kidney disease [ACE D allele was also associated with increased risk of minimal change nephritic syndrome in Asians (OR [95%CI]=1.38[1.07-1.79]) [>50]. In a meta ->1 studies [250], the ACE DD genotype was associated with susceptibility to, and progression of, IgA nephropathy with stronger associations in Asians than in Caucasians.The role of the ablished . In 2847function . The ACEn or CKD , 141. In disease . The ACEACE I/D polymorphism and blood pressure salt-sensitivity. Hypertensive patients carrying the II genotype had higher ambulatory blood pressure increase under high salt intake than patients carrying the DD genotype [ACE I allele was therefore associated with higher salt-sensitivity than the D allele. This is in line with one study including 66 hypertensive patients in Japan [ACE I/D polymorphism confers blood pressure sensitivity to salt intake.Only few studies have analyzed the association between the genotype . In thisgenotype , the ACEin Japan  and within Japan , whereasin Japan  and 188 in Japan  hypertenet al. identified 11 studies having analyzed the role of the ACE I/D polymorphism on blood pressure response to ACE inhibitor treatment, but the results were inconsistent [ACE I/D polymorphism was not associated with blood pressure response to ACE inhibitor (perindopril) treatment, or with the long-term risk of stroke and cardiac events, in 5,688 participants to the PROGRESS trial [ACE I/D polymorphism did not influence blood pressure response to treatment [ACE I/D polymorphism did not significantly predict fatal and nonfatal coronary heart disease, myocardial infarction, stroke or all-cause mortality [ACE I/D polymorphism was not associated with ACE inhibitor treatment benefit . By contrast, in this same study, ACE inhibitor treatment benefit was associated with variants in the AT1 receptor and BK1 receptor genes [ACEI/D polymorphism is unlikely to be clinically relevant in predicting response to antihypertensive treatment or risk of cardiovascular disease in the absence of renal dysfunction.In an overview published in 2006, Arnett nsistent . In partSS trial . In a streatment . In the ortality . Similarortality , the ACEor genes . These rACE DD genotype is associated with reduced renal benefit from ACE inhibitor treatment in patients with type 1 or type 2 diabetic nephropathy [ACE D allele was associated with poor renal prognosis in the placebo group, whereas no such association was found in the losartan group, which suggests that losartan was able to correct the poor prognosis associated with the ACE D allele [DD genotype respond less well to ACE inhibitor treatment under conditions of high salt diet [DD genotype than in those carrying the ID and II genotypes under liberal sodium intake, but not under low sodium intake [ACE I/D polymorphism and dietary sodium intake for their effects on blood pressure and renal function.The situation is quite different in the presence of renal dysfunction or in the presence of high salt intake . Multiplhropathy , 261. InD allele . Patientalt diet . In 27 hm intake . Similarm intake . These rACE I/D polymorphism. The D allele of the ACE I/D polymorphism is clearly associated with increased risk of diabetic nephro-pathy. By contrast, the associations of the ACE I/D polymorphism with hypertension and cardiovascular disease have been inconsistent. The ACE I/D polymorphism is a useful test to predict the renoprotective effect of ACE inhibitor or angiotensin receptor blocker treatment in patients with kidney disease [ACE I/D polymorphism in predicting future risk of cardiovascular events or blood pressure response to ACE inhibitors in the absence of renal dysfunction.In summary, ACE is an enzyme involved in the renin-angiotensin-aldosterone and kinin-kallikrien pathways involved in blood pressure control. ACE inhibitors are used to treat cardiovascular and renal diseases, including hypertension. The high inter-individual variability in circulating ACE levels is explained, in large part, by the  disease . There i2.4.2 MTHFR is located on chromosome 1p36.22 and encodes the methylenetetrahydrofolate reductase. This enzyme is a key enzyme for folate homeostasis and catalyzes the conversion of 5,10-methylentetrahydrofolate to 5-methyltetrahydrofolate, the substrate for the conversion of homocysteine to methionine [MTHFR includes 11 exons [thionine . The lat11 exons  and seve11 exons . MTHFR genetic variations cause MTHFR deficiency, neural tube defects and some evidence suggests an association with cancer [MTHFR genotype and coronary heart disease have provided conflicting results [h cancer . Severe h cancer . Meta-an results . These aMTHFR polymorphisms have been associated with an increased risk of ESRD [CKD patients and to a major extend patients on dialysis suffered from elevated homocysteine , which m of ESRD  and incr of ESRD .MTHFR and CKD patients at an earlier stage of ESRD are also available. MTHFR variants have been associated with accelerated chronic decline in renal function. The influence of MTHFR variants C677T and A1298C on progressive loss of kidney function has been analyzed in 821 African-Americans with hypertensive nephrosclerosis from the longitudinal National Institute of Diabetes and Digestive and Kidney Diseases African-American Study of Kidney Disease and Hypertension (AASK) Trial [MTHFR gene polymorphisms with the presence and the severity of renal disease was investigated in 100 patients with CKD and 120 healthy controls Tunisians. C677T and A1298C polymorphisms were not associated with the presence of non-ESRD renal disease [MTHFR genotypes. In patients with ESRD with the mutant C677T TT genotype, the adjusted hazard ratio for mortality was 2.27 . The relationship was not significant in patients with advanced CKD. The overall relationship between the A1298C polymorphism and mortality was significant neither in patients with ESRD nor in patients with advanced CKD [e.g., Cyprus [MTHFR variants and the risk of CKD. However, the MTHFR region was not uncovered as associated with CKD or other renal traits in recent GWAS [Data on the association between K) Trial . In thisK) Trial . This re disease . In a su disease . Frequennced CKD . Studies, Cyprus , Poland , Cyprus ) reporteent GWAS , 44, 141MTHFR mutations influence kidney function are possibly mediated by homocysteine. Elevated levels of homocysteine are associated with increased risk of thrombosis and MTHFR genetic variants are associated with inherited thrombophilia states [MTHFR C677T polymorphism with renal vascular sclerosis was compared between patients whose renal biopsies showed vascular disease  and patients without vascular sclerosis at the biopsy [MTHFR C677T mutant polymorphism was associated with vascular sclerosis . These results suggest that patients without hypertension and diabetes but with idiopathic renal vascular disease might be predisposed to vascular scarring by thrombophilic gene mutations [Some of the mechanisms by which a states . Patiente biopsy . In 34 putations . The athutations , while outations , 284 andutations .MTHFR, homocysteine and kidney function across different settings can also be confounded by other environmental factors such as folic acid intake and fortification policy. MTHFR C677T is especially associated with moderate elevated homocysteine concentration in setting of marginal folate intake [The comparison of the relationship between e intake .MTHFR and blood pressure were already suggested before associations from GWAS on blood pressure and hypertension were available. For example, in 2004, a meta-analysis of studies comparing women with and without hypertension in pregnancy for the MTHFR C677T suggested that the T allele increases the risk of severe diastolic hypertension during pregnancy [MTHFR region has been uncovered as a loci associated with blood pressure or hypertension in multiple GWAS. A GWAS was conducted in 18,738 Caucasian women who participated in the Women’s Health Study cohort study and were free of hypertension at baseline. blood pressure progression at 48 months and incident hypertension during the entire follow-up according to the different genotypes were assessed [MTHFR rs1801133 had a significant association with blood pressure progression. The OR for blood pressure progression (95%CI) for MTHFR rs1801133  was 1.05 (1.00–1.10), but this association nor the association with incident hypertension remain significant after adjustment for multiple testing [Contrary to some of the other pharmacogenes discussed in this review, associations between regnancy . Neverthassessed . MTHFR r testing .-13) in the MTHFR/CLCN6/NPPB locus. Carriers of the G allele at this polymorphism were less likely to have hypertension compared to carriers of the A allele . The rs17367504 is located in an intron of the MTHFR gene but in a region with many plausible candidate genes, including MTHFR, CLCN6, NPPA, NPPB and AGTRAP [MTHFR gene was also uncovered in a recent GWAS conducted in Chinese Hans, but the association was limited to diastolic blood pressure [MTHFR rs17367504  among Japanese subjects (N=1526) [Analyses from the GlobalBPGen and CHARGE consortia data showed an association between systolic or diastolic blood pressure and variant (rs17367504) near the MTHFR gene  .MTHFR region was also identified in the first large-scale (N=2020) experiment using the new Illumina HumanCVD BeadChip (50K IBC array) in relation to mean 24-hour systolic and diastolic blood pressure (GRAPHIC Study) [MTHFR and CLCN6 and mean 24-hour diastolic blood pressure was found. Each minor allele of rs13306560 was associated with 2.6 mm Hg lower mean 24-hour diastolic blood pressure (P=1.2×10−8). Interestingly, this study also showed that a majority of the candidates previously associated with clinical measurements of blood pressure were not or only weakly associated with mean 24-hour blood pressure. The investigators stressed that mean 24-hour blood pressure has a higher heritability than clinic measurements and is probably more informative in gene discovery [The C Study) . A stroniscovery . UnfortuMTHFR gene is a causal gene for hypertension, it is worth noting that some recent candidate gene studies and GWAS did not replicate the association. For example, MTHFR gene polymorphisms C677T and A1298C were not risk factors for hypertension in a recent candidate gene study conducted among 150 Turkish participants [While this study further suggests that icipants  and thisicipants .MTHFR polymorphisms on blood pressure and hypertension could again be mediated, at least in part, by homocysteine. Homocysteine levels have been associated with hypertension and the different mechanisms leading to hyperhomocysteinemia-associated hypertension have recently been reviewed [MTHFR genotype. In a case-control study of 458 participants, an increased hypertensive risk was observed in MTHFR C677T TT carriers men with homocysteine level higher than 15 micromol/L  but not in those non-TT carriers men with homocysteine level higher than 15 micromol/L  [The influence of reviewed . Mechaniue=0.33) .MTHFR in general has been reviewed elsewhere [MTHFR related to blood pressure. We identified studies that did investigate the modification of the association between benazepril treatment (an ACE inhibitor) and blood pressure by MTHFR C677T. In 2005, Jiang S et al. investigated in Chinese hypertensive patients whether short-term blood pressure response to benazepril, was modulated by haplotypes re-constructed from both C677T and A1298C polymorphisms in MTHFR gene [MTHFR C677T was associated with baseline systolic blood pressure  and baseline diastolic blood pressure . MTHFR C677T was independently associated with increased diastolic blood pressure response (baseline minus post-treatment) to benazepril treatment , but not with systolic blood pressure response [MTHFR C677T polymorphisms may modify some of the blood pressure response to benazepril treatment.The pharmacogenomics of lsewhere . Below, HFR gene . A totalresponse . Thus, Met al. discussed elsewhere, studies have rarely considered the MTHFR C677T polymorphisms [MTHFR C677T polymorphism in 181 premature cardiovascular disease patients [et al. conducted an intervention study where 41 asymptomatic men with normal or high-normal ambulatory blood pressure were randomized to receive in a placebo-control, cross over study, 3 weeks of 5 mg folic acid/day or placebo. The investigators found a similar blood pressure response (decrease) to folate supplementation across MTHFR C677T genotypes [MTHFR genotypes have also been associated with risk of dyslipidemia and diabetes [Vitamin B12, B6, and B2 (riboflavin) are the main nutritional determinants of homocysteine. Intervention studies based on vitamin B supplementation have generally reported no effect on blood pressure. As Wilson orphisms . One stupatients . Among ppatients . Williamenotypes . It is wdiabetes -302.MTHFR. We suggest therefore that this is an area in need of further research investment. MTHFR is a key enzyme in folate and homocysteine metabolism. Selected MTHFR genetic variants cause MTHFR deficiency and are associated with neural tube defects and inherited thrombophilia states. Patients with impaired renal function have elevated homocysteine concentrations, and MTHFR polymorphisms have been associated with the risk of developing ESRD. In recent GWAS, the MTHFR locus was associated with blood pressure and/or hypertension, but not with renal function or CKD. As other plausible nearby blood pressure candidate genes exist  further studies are needed to determine whether MTHFR is indeed the causal gene. Homocysteine seems to explain only partially the associations between MTHFR polymorphisms and kidney function and blood pressure/hypertension. Some studies showed that MTHFR variants significantly modified the blood pressure response to antihypertensive drugs.We could not identify studies addressing salt sensitivity and Pharmacogenes have been mostly studied for their effects on drug metabolism, safety and efficacy. Less is known on the roles of pharmacogenes in disease susceptibility or kidney pathophysiology. More specifically, we consider that the role of pharmacogenes for endogenous substrates in relation to renal function and blood pressure needs more in-depth investigation. While the genome-wide meta-analyses (GWAS) have not identified the VIP pharmacogenes as being robustly associated with renal function, these initial explorations do not necessarily address the entire genetic variability of renal function or blood pressure . CKD is a growing public health burden worldwide and a better understanding of its pathophysiology is urgently needed, as are new therapeutic interventions. As illustrated in this paper, a substantial number of important pharmacogenes are associated with blood pressure and hypertension in humans. With the exception of VDR, the link with renal function is less clear, but this has been under-studied so far. Further studies are needed in this area because 1) the kidney is the major organ responsible for blood pressure control, and 2) renal function is an important determinant of the clearance of many drugs and other xenobiotics. This knowledge is important to better assess the role of pharmacogenes in health in general and to individualize treatment in particular.ACE I/D polymorphism is a useful test to predict the progression of type 1 or type 2 diabetic nephropathy [In our view, ACE inhibitors represent the first pharmacogenomic application at the nexus of renal pathophysiology and cardiovascular medicine. As detailed in this paper, ACE inhibitor treatment is clearly renoprotective. Furthermore, the hropathy  and alsovia blood pressure control and renal sodium handling . Lipid and drug metabolisms are also tightly interconnected via shared regulation by nuclear receptors such as PXR, CAR, VDR and GR [endobiotic sensor with roles in modulating inflammation as well as lipid, energy and vitamin D metabolisms [via its action on the transcription of the ABCB1 and CYP3A5 genes. For the other nuclear receptor, VDR, the link with blood pressure and renal function, in particular, is clear, as previously mentioned. We therefore choose VDR agonists, such as vitamin D analogs, as our second pharmacogenomic application at the nexus of renal pathophysiology and cardiovascular medicine.Among the selected pharmacogenes, two are nuclear receptors, namely VDR and PXR. The role of nuclear receptors in renal diseases has been recently highlighted with an emphasis on carbohydrate metabolism, lipid metabolism, immune response and inflammation. We hereR and GR . PXR wasabolisms . We hereCYP3A genes, ABCB1 and PXR, and that this effect is tissue specific [e.g., one-week low salt versus one-week high salt, response to i.v. NaCl infusion, response to an i.v. diuretic dose, etc). Furthermore, as these research protocols are quite demanding, sample sizes have usually been very small, with rarely more than 100 participants, so that studies have been underpowered to detect small effect sizes. We are therefore lacking a salt-sensitivity test suitable for large scale population-based studies. Baring these limitations in mind, several pharmacogenes are currently considered as being salt-sensitivity genes . Yet, we know little on the role of dietary salt intake on the expression of these pharmacogenes. Furthermore, little has been done to explore the role of salt intake on the pharmacokinetics and pharmacodynamics of drugs in general and, of drugs used to treat essential arterial hypertension and renal dysfunction in particular. If salt intake plays an important role, this may have clinical consequences in adapting drug doses to achieve better treatment safety and efficiency, while maintaining optimal preventive strategy to reduce overall cardiovascular risk. We therefore choose ‘reduced dietary salt-intake’ as our third pharmacogenomic application at the nexus of renal pathophysiology and cardiovascular medicine for its potential to reduce cardiovascular risk in salt-sensitive individuals.Several dietary factors may influence the expression and activity of pharmacogenes, among which grapefruit juice and herbal extracts such as St John’s wort stand out . Dietaryspecific . More stspecific -306. Lowspecific , 307. AmAs previously suggested , we suppAs some of the pharmacogenes also act as xenobiotic sensors, multiple interactions between genes, drugs as well as other xenobiotics and dietary factors are expected. This underscores the need for large-scale international consortia to decipher the complex interplay between xenobiotics, endobiotics and pharmacogenes on kidney function and diseases in humans.


To investigate the issue further, a team of U.S., British, and Chinese researchers assessed the link between blood pressure and PM2.5 emitted during indoor burning of wood, coal, or crop residues used for heating and cooking . These fuels and the poorly vented, inefficient stoves in which they are typically burned are a significant source of indoor air pollution exposure for almost half the world’s population.Elevated blood pressure leads to increased risk of cardiovascular disease, stroke, and kidney disease. Indoor air pollution, including exposure to fine particulate matter  and 9 to 492 µg/m3 in summer (mean 55 µg/m3); by comparison, the EPA 24-hour standard is 35 µg/m3. There was a significant association between increasing PM2.5 exposure and elevated blood pressure in women over age 50, with an increase in systolic blood pressure of 4.1 mmHg and an increase in diastolic blood pressure of 1.8 mmHg for each log-µg/m3 increase in PM2.5.The 24-hour PMFew studies have investigated the link between chronic PM exposures and the development of overt hypertension. However, the authors estimate, based on previous reports, that reducing systolic blood pressure by 4 mmHg among Chinese women aged 50–59 could lead to an 18% decrease in coronary heart disease, a 22% decrease in stroke, and about 231,000 fewer premature deaths among Chinese women over age 50. They say such reductions could be accomplished if households switched from open fires and other inefficient cooking and heating devices to more efficient stoves (such as improved wood-burning cookstoves) and less polluting fuels (such as liquefied petroleum gas).


Background and Objective. We examined the association of elevated ankle blood pressure (ABP), together with exercise blood pressure, with incident cerebrovascular (CV) morbidity and mortality in a prospective follow-up study of 3,808 patients. The results were compared with pulse pressure, another indicator of arterial stiffness. Methods. Patients with normal ankle and exercise brachial blood pressures were taken as the reference group. Pulse pressure was considered as quartiles with the lowest quartile as the reference category. Results. A total of 170 subjects had a CV event during the follow-up. Multivariate adjusted hazard ratio of a CV event was 2.24  in patients with abnormal ABP. The pulse pressure was significant only in the model adjusted for age and sex. Conclusion. The risk of a future CV event was elevated already in those patients among whom elevated ABP was the only abnormal finding. As a risk marker, ABP is superior to the pulse pressure. High ankle blood pressure (ABP) might be an emerging risk marker for early subclinical damage of arterial vessels evaluated as elevated ankle blood pressure alone , 2 or in The pulse pressure (PP) has been used as a crude indicator of arterial stiffness –17. The  Elevated ABP may provide a pivotal opportunity to identify persons at high risk of stroke or TIA. Accordingly, the main aim of the present study was to assess the utility of ABP, together with exercise brachial BP, as a predictor of CV events in a prospective setting. The second aim was to investigate whether the elevated ABP predicts CV events better than the pulse pressure. Both measurements reflect aortic stiffness. We hypothesized that the ABP would be superior to the pulse pressure for screening purposes.This prospective follow-up study was initiated in August 1989. The methods of baseline data collection have been described in our previous paper [The ankle and brachial blood pressures were obtained simultaneously after a 5 min rest in supine position using the Doppler sonography for the ABP and the standard mercury sphygmomanometer for the left arm blood pressures. Subjects were divided to five groups based on the ABP at rest and exercise blood pressures (EBPs) at a moderate exercise level  as shown in the flow chart . The reference group consisted of “normal” patients with normal ABP (<175 mmHg) and normal systolic EBP (≤215 mmHg). Group 2 consisted of patients with elevated ABP (≥175 mmHg), but normal EBP. Group 3 had elevated ABP and exaggerated EBP (>215 mmHg). Patients in group 4 had elevated EBP, but the ABP was normal. The discrepancy between the ABP and EBP indicates significant atherosclerotic changes in conduit vessels. Group 5, the unclassifiable group, consisted of patients, who could not tolerate the moderate exercise level. The follow-up was 16 years, until the end of 2007 using record linkage of the study data with the National Hospital Discharge Register and the National Causes of Death Register. The endpoint was a major CV event, that is, death due to CV, nonfatal stoke, or a transient ischemic attack (TIA). The 9th (until 31.12.1995) and 10th versions of the International Classification of Diseases (ICD-9 and ICD-10) were used for coding of causes of death and hospitalizations. We took as CV events the ICD-9 codes 431, 436, 4330A, 4331A, 4339A, 4340A, 4341A, 4349A, and 435 or the ICD-10 codes I61, I63-I64. G45. These registers cover all deaths and hospitalizations in Finland. Thus, the coverage of follow-up was 100% for symptomatic stroke events leading to hospitalization or death in Finland. It is however likely that all TIAs have not been hospitalized and those treated on an ambulatory basis are not identified as CV events in the present study. Altogether, 170 CV events were observed during the follow-up. Of them, 31 were fatal. As a whole, the study consisted of 53,044 person-years of followup.t-tests were used for comparisons of normally distributed variables, between persons with and without a CV event during the follow-up. Categorical variables were compared using chi-square tests. Data are expressed as mean ± SD for continuous variables or counts and proportions for categorical variables. The following cardiovascular risk factors were dichotomized: early parental cardiovascular death (yes or no), self-reported elevated cholesterol , self-reported elevated blood glucose , and current smoking (yes or no). Age, BMI, smoking , and blood pressure (mmHg) were handled as continuous variables. Student's  Associations between the blood pressure groups, and CV mortality and morbidity (first events) were analyzed using Kaplan-Meier curves and log-rank tests. Cox proportional hazards models were used for estimating the multivariate-adjusted independent associations of the blood pressure groups or the quartiles of pulse pressure with the risk of a CV event. Results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs) compared to the “normal” group or to the lowest quartile of pulse pressure. The basic models were adjusted for age and sex. The larger models were further adjusted for BMI, physical working capacity (METs), self reported blood glucose and cholesterol, current smoking, resting brachial systolic blood pressure, and early parental history of cardiovascular disease. The statistical analyses were carried out with R (Version 2.11.1).Baseline characteristics of the study participants are outlined in P = .001, log rank test) throughout the 16 years of follow-up.The patients with elevated ankle blood pressure with or without exaggerated exercise blood pressure had 2.6-2.7-fold risk of a CV event compared with the reference group in the age- and gender-adjusted model . In the r2 = 0.48). The correlation was lost, however, when obstructive changes were observed in the conduit vessels (Group 4) (r2 = 0.11). The risk of a CV event by quartile of pulse pressure is shown in Pulse pressures in the five blood pressure groups were 42.7 ± 11, 54.4 ± 15, 58.5 ± 14, 49.0 ± 14, and 52.6 ± 16 mmHg, respectively. Correlation between the pulse pressure and the ankle blood pressure in the blood pressure groups I–III was high (The main finding of our study was that ABP, when considered together with EBP in a physiologically meaningful way, improved the prediction of incident CV events independently of classic risk factors. The healthy group with normal ABP and EBP had the best prognosis, while the group with poor exercise tolerance had clearly the worst prognosis. For groups II–IV, the Kaplan-Meier curves were overlapping. Furthermore, ABP was a better predictor than the pulse pressure. Increased aortic and conduit vessel stiffness with high pressure pulsatility may be the explanation for our finding. The elevated ABP may be a useful surrogate marker for central and conduit arterial stiffness.These findings extend our understanding of the behaviour and clinical significance of the ABP. In the recent PARTNER study , individ When the conduit vessels are free of flow limiting atherosclerotic stenoses, the main determinants of ABP are systolic blood pressure, enhanced pulse pressure, and local changes caused by rigidity of the arteries in the lower extremities. In these conditions, we can draw epidemiologic conclusions from ABP per se without indexing it to the brachial systolic pressure. The discrepancy between the ABP and exercise blood pressure may disclose those patients among whom stenotic changes along the conduit vessels decrease the ABP. The good correlation between PP and ABP is lost when the stenotic changes limit the flow in the conduit vessels. The PP as a crude index of central arterial stiffness is not only hampered by age and heart rate but also by flow limiting atherosclerotic changes in the conduit vessels. That may explain why the peripheral PP is differently related to the risk of CV events in the literature –26, 30 aA strength of our study is the large sample size and the long follow-up period of 16 years. Also, in Finland the record linkage to the National Hospital Discharge Register and the National Causes of Death Register has good accuracy and coverage . Some liIn conclusion, our results suggest new ideas about surrogate markers of subclinical vascular damage. The elevated ABP reveals better than PP the early adverse vascular changes, and the discrepancy between ABP and EBP discloses those patients in whom the atherosclerotic changes have propagated to the arterial lumen causing flow limiting stenosis. The ABP measurement may help us to better identify the patients who have the greatest risk for a CV event.


The aim of this study was to investigate the association of sex hormone-binding globulin (SHBG) and hypertension in a Swedish population.The study is based on a random sample of a Swedish population of men and women aged 30–74 years . Total testosterone, oestradiol and SHBG were measured in 2,782 participants. Free androgen index was then calculated according to the formula FAI=100 × /SHBG. Hypertension was diagnosed according to JNC7.In men, but not in women, significant association between SHBG and both diastolic (diastolic blood pressure: β=−0.143 p<0.001) and systolic blood pressure (systolic blood pressure β=−0.114 p<0.001) was found. The association was still significant after adjusting for age, body mass index (BMI), homeostatic model assessment insulin resistance (HOMA-IR), triglycerides, high density lipoproteins (HDL) and C-reactive protein (CRP) . An inverse association was observed between SHBG and hypertension in both men (B=−0.024 p<0.001) and women (B=−0.022 p<0.001). The association was still significant in women older than 50 years after adjustments for age, BMI, physical activity, CRP and alcohol consumption .In conclusion, these results show a strong association between SHBG and blood pressure independent of major determinants of high blood pressure. This association might be addressed to direct effects of SHBG in endothelial cells through the receptor for SHBG. If this is confirmed by other observational and experimental studies, it might become a new field for the development of therapies for lowering blood pressure. Studiosterone . Secondlosterone ,9-13. Thosterone ,15, indiosterone .A sizeable fraction of circulating testosterone is bound to sex hormone-binding globulin (SHBG); however, it is still not established if the observed link between the total testosterone and several cardiovascular risk factors  mirrors an effect of free circulating testosterone, or whether SHBG plays a more direct role. A recent study by Ding et al.  showed aThe purpose of this study was therefore to investigate the association between hypertension and SHBG, in both men and women in a Swedish population.Between 2001 and 2005 a random sample of subjects, aged 30–74 years residing in two municipalities in South-western Sweden, were enrolled in the study . All indDetails on the study protocol have been published previously . StandarLTPA was characterised based on the response of questionnaire item: ‘How much physical activity do you engage in during your leisure time?’  The quesThe nurses measured the standard resting blood pressure twice, one minute apart after five minutes rest with the subjects in a supine position. . The mean value of the two blood pressure readings was used for the analyses.Samples including plasma and serum were drawn after an overnight fasting and were immediately frozen at −82°C. In participants without known diabetes mellitus (DM), an OGTT was performed. Total cholesterol, HDL-cholesterol, LDL-cholesterol and S-triglycerides were analysed using standard procedures.Total testosterone was analysed with kits Beckman Coulter 2003, 386982A (CV=7-8%) and estradiol (CV=9-15%) and sex hormone-binding globulin (SHBG) (CV=5%) were analysed by kits Siemens Immulite 2000XPi . These a2. Insulin resistance was estimated using the homeostatic model assessment for insulin resistance (HOMA-IR) [Impaired fasting glucose, impaired glucose tolerance and diabetes mellitus were defined according to the WHO criteria . HyperteHOMA-IR) .All participants gave signed informed consent before being enrolled in the study, and the Ethical Committee at the University of Gothenburg, Sweden, approved the study.Standard methods were used for descriptive statistics. The association between SHBG, sex hormones and blood pressure was investigated in simple and multiple linear regression models after exclusion of subjects treated with blood pressure lowering drugs. Logistic regression analyses were performed to estimate the association between hypertension and sex hormones-SHBG. Associations were expressed as regression coefficients (B) and odds ratios (OR), respectively, both with 95% confidence intervals (CI). General linear models were used to estimate differences (CI) between continuous variables. Theoretical multivariate models were used to estimate the role of possible confounders on the investigated association. All analyses were two-sided and the significance was accepted if p<0.05. All analyses were performed using SPSS Statistics for Mac. In order to evaluate the strength of the association for each possible risk factors of hypertension, we standardised the variables in consideration by the formula SV=V/SD, where SV is the standardised variable. V is the value of the variable and SD is the standard deviation. We then ranked their association with hypertension by the regression coefficient β in the logistic regression analyses.The characteristics of the study population are presented in Table In our population 271 (10%) individuals were under treatment for hypertension. The association between SHBG and blood pressure after excluding subjects on medication for hypertension is presented in Table Age-adjusted differences of SHBG concentrations in different blood pressure categories in accordance with JNC7 are presented in Figure The associations between quartiles of SHBG and hypertension are presented in Table In Table The interaction between sex hormones, SHBG and hypertension was investigated in a logistic regression model, but no significant interaction was found. The interaction between age and SHBG in the hypertension and blood pressure was also investigated with regression models, but no significant difference was found.In this cross-sectional study, a strong inverse association between blood pressure and SHBG was observed. Post-menopausal women with hypertension had significantly lower SHBG concentrations, and this association was significant even after adjusting for major risk factors for hypertension such as age, BMI, diabetes and insulin resistance. In men, we observed an inverse association between systolic blood pressure and SHBG. This association was independent of major confounders. Both these findings indicate that low concentrations of SHBG may have independent negative effects in the control of blood pressure.To our knowledge this is the first study to estimate the specific role of SHBG in blood pressure control. There are some publications concerning the association between hypertension and SHBG in men, but very few in women. The majority of studies, aimed to estimate the effects of testosterone on blood pressure in men, provided information about the level of SHBG. This was done in order to estimate the concentrations of free testosterone. However, only a few studies have presented information about the association between SHBG and hypertension. In a prospective study in men, aimed to investigate the role of sex hormones in hypertension, Khaw et al.  observedSome gender differences were, however observed in our study Figure . In accoWe did not found studies comparing the strength of the association between SHBG and hypertension with other risk factors for hypertension. In order to compare the SHBG with other conventional risk factors for hypertension, we standardized age, BMI, HOMA-IR and SHBG. In our study a weak association between insulin resistance and hypertension was observed in men were SHBG had stronger association with hypertension than HOMA-Ir.et al. [Tot-T but not free testosterone was associated with hypertension in our population. Testosterone deficiency has been indicated as a risk factor for obesity and cardiovascular diseases. The question as to whether T has a direct effect on blood vessels remains to be investigated. We cannot confirm the vasodilatative effects of free testosterone that were shown by Webb et al. . Our reset al.  speculatet al. . This reet al. . Whetheret al.[In accordance with previous studies, we found a positive linear association between SHBG and age in men while in women the association is inverse before 50 years of age ,32. The et al..This was a large population based study that included both men and women. Therefore, we could compare the association of oestradiol, SHBG and testosterone in both men and women. The study had a high participation rate of 76%, including a younger middle-aged population. The diagnosis of hypertension was précised with the trained nurse. In this large study population, we also had information about the medication influencing the blood pressure that gave us the possibility to exclude subjects with blood pressure lowering medication or with hormonal medication that could have influenced the analyses. Blood samples were collected in the morning, thereby avoiding influences of circadian changes in the hormonal concentrations.A potential weakness of this study might be the lack of information with regard to menopausal status. Still, the use of 50 years as cut-off point for menopause is supported by findings from previous studies ,35. It sThese results show a strong association between SHBG and blood pressure independent of the components of metabolic syndrome and inflammation. This association might be explained by a direct effect of SHBG in endothelial cells through the receptor for SHBG. If others confirm this it might become a new field for the development of therapies for lowering blood pressure.SHBG: Sex hormone-binding globulin; FAI: Free androgen index; JNC: Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure; BMI: Body mass index; HOMA: IR-homeostatic model assessment of insulin resistance; CRP: c-reactive protein; HDL: High density lipoprotein; LDL: Low density lipoprotein; Tg: Triglycerides; LTPA: Leisure time physical activity; OGTT: Oral glucose tolerance test; WHO: World Health Organisation; OR: Odds ratio; CI: Confidence interval; SD: Standard deviation.The authors report no competing interest. The authors alone are responsible for the content and writing of this paper.BD prepared the data, performed the statistical analyses, drafted the manuscript and took part in conceiving the study. TR and PAJ offered their expertise in endocrinology and metabolism questions. CAL worked on preparing data and offered expertise in statistical analysis. LR conceived the study and acquired the data. UL conceived and coordinated the study, as well as acquired the data. All authors took part in the design of the study, the interpretation of data, the revision of the manuscript, and read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/13/30/prepub


Randomized trials have demonstrated the effectiveness of the Dietary Approaches to Stop Hypertension (DASH) program for lowering blood pressure; however, program participation has been limited in some populations. The objective of this pilot study was to test the feasibility of using a culturally modified version of DASH among African Americans in an underresourced community.This randomized controlled pilot study recruited African Americans in 2 North Carolina neighborhoods who had high blood pressure and used fewer than 3 antihypertension medications. We offered 2 individual and 9 group DASH sessions to intervention participants and 1 individual session and printed DASH educational materials to control participants. We collected data at baseline (March 2010) and 12 weeks (June 2010).2. Intervention participants attended 7 of 9 group sessions on average. After 12 weeks, we observed significant increases in fruit and vegetable consumption and increases in participants’ confidence in their ability to reduce salt and fat consumption and eat healthier snacks in intervention compared with control participants. We found no significant decreases in blood pressure.Of 152 potential participants, 25 were randomly assigned to either the intervention (n = 14) or the control (n = 11) group; 22 were women, and 21 were educated beyond high school. At baseline, mean blood pressure was 130/78 mm Hg; 19 participants used antihypertension medications, and mean body mass index was 35.9 kg/mImplementation of a culturally modified, community-based DASH intervention was feasible in our small sample of African Americans, which included people being treated for high blood pressure. Future studies should evaluate the long-term effect of this program in a larger sample. Hypertension is a prevalent risk factor for chronic disease . NationaDespite the known benefits of DASH and wide availability of free DASH materials, the average US diet does not conform to DASH recommendations . BarrierWe used a single-cohort RCT design to test the feasibility of our culturally tailored DASH materials and intervention strategies. We examined whether we would be able to achieve a participation rate that compares well with those of other DASH studies and whether our sessions would be well attended. As a secondary study goal, we also evaluated the expected effect size for changes in blood pressure and other laboratory and anthropometric measures, changes in behavior, and confidence in ability to change eating habits, to be used for planning for a larger trial to test the culturally tailored DASH intervention. All procedures were approved by the Wake Forest School of Medicine Institutional Review Board, and the study was registered in clinicaltrials.gov (no. NCT00964483). The 12-week intervention was conducted from March 2010 through June 2010.We conducted this study in 2 primarily urban, financially underresourced neighborhoods (zip codes 27101 and 27105) in Forsyth County, North Carolina. Compared with the county, the 2 zip code areas have a lower median household income , a greater proportion of residents earning less than $50,000 annually (72% in 27101 and 62% in 27105 vs 52.8% in county), and higher unemployment rates (8.4% in 27101 and 27105 vs 7.7% in county) –15. Both2) because the DASH diet could cause weight loss and morbidly obese people (BMI ≥45.0 kg/m2), for whom a weight-loss diet and/or pharmacologic or surgical intervention would be indicated. After a brief telephone interview to determine eligibility, we invited potential participants to an information session. People interested in the study and qualified on the basis of blood pressure readings taken at the information session provided informed consent and were scheduled to visit the Wake Forest University General Clinical Research Center, where they were assessed for height and weight, blood pressure, and medical history through standardized protocols. Participants also had a fasting blood draw to obtain measures of glucose and creatinine. People still eligible and wishing to participate had a second visit, during which they were randomly assigned to either the intervention or control group and completed additional questionnaires. The 12-week recruiting and screening process took place from January 2010 through March 2010.We recruited participants through mass media advertisements, mailings to people identified on existing lists and by community contacts, and referrals from community partners. Eligibility criteria were 1) self-identifying as African American; 2) being a minimum age of 21 years; 3) self-reporting a primary residence in target zip codes; 4) having a systolic blood pressure of 120 mm Hg to 159 mm Hg, diastolic blood pressure of 80 mm Hg to 99 mm Hg, or both; 5) taking fewer than 3 antihypertensive medications; 6) willing to accept random assignment; and 7) willing to attend intervention sessions at a centralized location. We excluded people who had diabetes, renal disease, heart failure, alcohol or substance abuse, dementia, or schizophrenia. We also excluded underweight people   and the The modified intervention was informed by social cognitive theory (SCT), which posits that engaging in behavior change requires that the social and physical environments support that change . ObservaThe modified DASH materials were designed to increase participants’ knowledge of community food sources and DASH benefits and to increase skills for preparing meals in accordance with DASH. The targeted behavioral goals were to increase dietary consumption to 9 to 12 servings of fruits and vegetables per day and 2 to 3 servings of low-fat dairy products per day and to decrease fat consumption to less than 25% of total energy, saturated fat consumption to less than 7% of total energy, and sodium consumption to less than 2,300 mg per day ,19. The Group sessions included discussion and focused on selecting foods and preparing meals in accordance with DASH. They were delivered by a dietitian at a local church that had classrooms and a large kitchen. Participants also practiced meal preparation skills in 4 sessions, assisted by a professional chef.Control participants attended 1 individual counseling session with the study physician and dietitian and received 2 NHLBI booklets on lowering blood pressure and following the DASH diet ,20. ContWe collected data at baseline (March 2010) and 12 weeks (June 2010). All measures were collected at both visits. Because our main objective was to test the feasibility of the modified DASH intervention, primary outcomes of interest were process measures, including participant willingness to engage in various aspects of the study and changes in the targeted dietary behaviors that could lead to changes in blood pressure . We assessed participant willingness to engage in aspects of the study by the number of people who participated in study screening and enrollment and attended study activities, including intervention sessions and data collection visits. We used the Block Fat/Sugar/Fruit/Vegetable Screener  to assesSecondary outcomes of interest, which were examined to determine effect sizes for a larger RCT, included measures of blood pressure, BMI, waist circumference, lipids, and creatinine. All secondary outcomes were measured at baseline and 12 weeks; blood pressure was also measured at week 6 for intervention participants only. Phlebotomy and laboratory measures were performed by trained clinical staff.t tests for continuous variables and χ2 tests for categorical variables to compare baseline characteristics of participants in the control and intervention groups. Analyses of covariance were used to compare outcomes between intervention and control groups, adjusted for baseline measures. Significance level was set at .05.We performed all analyses using SAS 9.2 . We used We screened 152 potential participants . We excl2.  of the 9 group intervention sessions. We found no significant differences overall or within groups between baseline and follow-up for targeted dietary behaviors. Compared with control participants, intervention participants reported significantly greater increases in confidence in their ability to reduce salt and fat consumption and to consume healthier snacks . DietaryWe did not observe significant pre–post changes in systolic or diastolic blood pressure  in the 2Within a limited time, we were able to screen 152 potential participants and randomize 25 (16.4%). Seventy-eight percent of potential participants invited to an information session attended, and 90% of potential participants who attended the session consented to further screening. Of people screened, 54% were eligible for and randomized into our study. Our screening and enrollment rate is similar to the rate of racial/ethnic minority participation in the original DASH study. The original DASH study screened 8,775 people and found 459 eligible (5.2%) .Although not significant, largely because of small sample size, the decreases in blood pressure found in our study are similar to those found in highly controlled feeding studies . In the original DASH study, 459 participants who had untreated systolic blood pressure of less than 160 mm Hg and untreated diastolic blood pressure of 80 to 95 mm Hg were provided all meals; the study showed a 5.5 mm Hg decrease in mean systolic blood pressure and a 3.0 mm Hg decrease in mean diastolic blood pressure after 8 weeks (after subtracting the effects of the control diet) . The PREAlthough feeding studies and carefully controlled clinical trials have shown the positive effect of DASH on blood pressure, DASH data from community-based trials are limited. The translation of DASH into community-based settings has shown that blood pressure decreased in participants who attended at least 6 of 8 sessions  and adheAnother study of DASH among African Americans highlighted the importance of practical problem solving and knowledge acquisition to increase adherence to DASH . Our stuOur study had several limitations. It had a small sample size. A larger sample might have shown significant differences between intervention and control groups for blood pressure and other measures. Our study was conducted among African Americans in a primarily urban community in North Carolina, which could limit its generalizability. We had difficulty recruiting eligible participants because the sample was limited to African American adults who had hypertension but not diabetes. Of 152 potential participants, 33 were excluded because of diabetes. Given the high prevalence of multiple chronic conditions among African Americans, future studies should identify methods for translating DASH in this population. Studies evaluating the DASH eating plan among people who have diabetes have noted an inverse association between adherence to DASH and measures of blood glucose and cholesterol levels . AdditioAmong adults who reported hypertension in the 1999–2004 National Health and Nutrition Examination Survey, only 22% reported eating a diet compatible with DASH; African Americans were 29% less likely than other population subgroups to report a DASH-compatible diet . Further