SLC35F3 which encoded a thiamine transporter was a new candidate gene for hypertension. The goal of this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) in the SLC35F3 gene and hypertension in a Chinese population. Sanger sequencing was performed in 93 samples to find SNPs in coding regions and intron–exon boundaries in the SLC35F3 gene. We found eight genetic variants in the coding regions of SLC35F3 and subsequently genotyped a non-synonymous variant rs34032258 (C > G) in 1060 hypertension patients and 1467 controls. After adjusting for age and gender, multivariate analysis of covariance showed that the variant was associated with hypertensive traits. In detail, diastolic blood pressure (DBP) was 8 mmHg higher, blood urea nitrogen was 12 mmol/L higher, and creatinine was 15 mmol/L lower in G/G group compared with C/C group . Further study suggested that C/G+G/G had higher DBP than C/C genotype in those whose DBP ≥ 90 mmHg . No significant difference has been found in systolic blood pressure between different genotypes. Additionally, in the subgroup of obesity, allele distribution of this variant has shown significant difference between hypertensive patients and normotensive controls (p = 0.018). In conclusion, we found that the rs34032258 in the SLC35F3 gene was associated with high blood pressure and may increase the risk of hypertension. The new hypertension-susceptibility locus may involve in the pathogenesis of hypertension and indicate some novel treatment implications.A recent study suggested that  The SLC35F3 mRNA was expressed at the highest levels in the adult cerebellum  group of transporters transports organic or inorganic molecules across cell or organelle membranes . Nearly families . Membersies A–F; and are pies A–F; . Geneticrebellum . Up to nSLC35F3 gene in 93 hypertensive patients by Sanger sequencing. Subsequently, the most suspicious variants were further genotyped by TaqMan-MGB assays in a total of 2527 participants, including 1060 hypertensive patients and 1467 normotensive controls. All of the participants were examined at Shanghai Ruijin Hospital. Every participant signed a consent form, and the study was approved by the hospital’s ethics committee.We conducted a two-stage strategy in this study. First, we scanned all the exons of 2) was calculated. Blood pressure was measured using a calibrated mercury sphygmomanometer with appropriate adult cuff size by well-trained examiners. Diagnosis of hypertension was based on a mean SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg on two occasions, and/or current usage of anti-hypertensive treatment.Age, gender, and medication usage were obtained from Shanghai Institute of Hypertension, Ruijin hospital. Height and weight were measured and BMI (kg/mTable 1. All the hypertensive patients (n = 1060) were selected in order to analyze the effect of the SNP on hypertensive traits (Table 2). Based on the results in Table 2, we selected 578 patients whose DBP ≥ 90 mmHg to further verify the relationship between the SNP and DBP . In addition, allelic frequencies of rs34032258 in different BMI levels were analyzed between 1467 controls and 1035 cases excluding 25 unavailable BMI data in case groups (Table 3). The effect of gender on SBP and DBP is shown in Table 4 including all the participants. Besides, the plasma of 344 hypertensive patients was available for ELISA test in order to verify the effect of this gene on blood thiamine in patients .During different analytic processes, the samples selected were diverse and the details are showed in Supplementary Table DNA was extracted from peripheral venous blood by lyzing red blood cells (RBCs) and digesting the remaining white cell pellet with proteinase K in accordance with the protocol . DNA samples were stored at –80°C until additional analysis was finished.SLC35F3 gene in 93 people was performed by Mapbioo Technology Company of China. Variant calling was carried out using Sequencher 5.1 and the annotation of the detected variants was checked on National Center for Biotechnology Information. We selected missense variant and designed primers for further genotyping.Sanger sequencing of 9 exons of the Genotypes were determined by pre-designed TaqMan Allele Discrimination Assay . TaqMan polymerase chain reaction (PCR) was performed on a 7900 Real-Time PCR system  in total volume of 2.5 μL consisting of 2.4 μL TaqMan PCR Master Mix  and 0.03 μL genomic DNA. Cycling conditions were 95°C for 30 s, and 50 cycles of 95°C for 15 s, and 60°C for 1 min.Thiamine B1 concentration was determined by using ELISA kit .t-test. Relations between categorical variables were examined by χ2 test. The association of examined SNPs with hypertension as a binary trait and BP as a continuous trait was done by Logistic and linear regression analyses, respectively, after adjusting for age, gender, and BMI. MANCOVA was used to compare the differences of BP, BMI, BUN, and Cr across the genotypes of rs34032258 after treating age and gender as covariates. The frequencies of genotypes between patients and controls were estimated by SHE2. Considering the impact of antihypertensive regimens, SBP and DBP were added by a fixed value of 10 and 5 mmHg, respectively, according to a previous report (p < 0.05 was considered to be significant.Continuous variables expressed as mean ± standard error (SE) were compared between two groups by unpaired s report . BMI wasSLC35F3. Among them, a missense variant, rs34032258, was detected with an allele frequency of 3.73% . However, SNPs previously reported to be associated with hypertension, either rs16842784 or rs17514104 was not found in the 93 samples .In 93 hypertension patients, eight genetic variants were found in the coding regions of Table 1. The distributions of age (p = 0.16) and gender (p = 0.24) did not differ significantly between patients and controls. BMI (p < 0.001), blood pressures (both p < 0.001) and Cr were significantly higher in patients than in controls as expected.The comparisons of the demographic and clinical features between hypertensive patients and normotensive controls are shown in Table 2. After adjusting for age and gender, the result from MANCOVA showed that rs34032258 was associated with DBP, BUN, and Cr. In detail, DBP was 8 mmHg higher, BUN was 12 mmol/L higher, and Cr was 15 mmol/L lower in G/G group compared with C/C group. In contrast, there was no difference in SBP and BMI between the two groups. Further study suggested that C/G+G/G had higher DBP than C/C genotype in those whose DBP ≥ 90 mmHg . Notably, we found that G allele frequency was significantly lower in hypertensive patients compared with controls in obesity group . No significant difference was found between controls and cases in underweight, normal weight, or overweight subjects.The associations of rs34032258 with BP, BMI, BUN, and Cr are shown in p > 0.05). Moreover, we examined the association of rs34032258 with SBP and DBP on a continuous scale by using linear regression analysis with age, gender, and BMI as covariates, and as expected, this variant was significantly associated with SBP and DBP (p = 0.033 and 0.010), especially for the latter (data not shown).We also performed logistic regression analysis to assess the association between hypertension and rs34032258 after adjusting confounding factors such as age, gender, and BMI. The result exhibited that compared to C/C genotype, C/G and G/G genotypes were not statistically associated with the risk of hypertension, with the corresponding odds ratio of being 1.18 (95% CI: 0.64–2.12) and 1.25 (95% CI: 0.60–2.52), respectively  and in control group .To discover the relation between sex and BP, one-way ANOVA analysis was performed and the result showed that male had higher DBP both in case group .No significant difference was detected in Thiamine B1 concentration between rs34032258 genotypes  cycle, catalyzing the oxidation of ketoglutaric acid to succinyl-CoA. In addition, it was a coenzyme for the pyruvate dehydrogenase complex (PDHC), converting pyruvate to acetyl-CoA. Clinical studies have shown that vitamin B1 might be associated with cardiovascular diseases . VitaminSLC35F3 mutation could result in the shortage of vitamin B1, then increased the blood pressure.One of the mechanisms might be that vitamin B1 could ameliorate the endothelium-dependent vasodilation . RoutineIn addition, vitamin B1 might be related to the cardiac function . ReductiSLC35F3 gene. These disease-causing variants could be in linkage disequilibrium with rs34032258.The present study may have some limitations. Although our study sample size was considerable, we might not be powerful enough to capture some potential rare but functional causal variants in the SLC35F3 gene and hypertension in a Chinese Han population. Further study is needed to discover the molecular mechanisms of SLC35F3 to blood pressure in order to improve clinical treatment. Our results may have implications for the pathogenesis and treatment of systemic hypertension.In summary, this study is the first to report the association between a missense variant, rs34032258, in the All the authors participated in the whole work. However, X-LZ and W-QH took on great work about design of the work and analysis, or interpretation of data. F-PY, K-DJ made contributions to perform the experiment and select samples. GH, S-NW took on drafting the work or revising it critically for important intellectual content. J-GW, P-JG agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Rationale: A critical reduction in central blood volume (CBV) is often characterized by hemodynamic instability. Restoration of a volume deficit may be established by goal-directed fluid therapy guided by respiration-related variation in systolic- and pulse pressure (SPV and PPV). Stroke volume index (SVI) serves as a surrogate end-point of a fluid challenge but tissue perfusion itself has not been addressed.Objective: To delineate the relationship between arterial pressure variations, SVI and regional brain perfusion during CBV depletion and repletion in spontaneously breathing volunteers.Methods: This study quantified in 14 healthy subjects  the effects of CBV depletion [by 30 and 70 degrees passive head-up tilt (HUT)] and a fluid challenge (by tilt back) on CBV (thoracic admittance), mean middle cerebral artery (MCA) blood flow velocity (Vmean), SVI, cardiac index (CI), PPV, and SPV.Results: PPV  and SPV  increased with progression of central hypovolemia manifested by a reduction in thoracic admittance , SVI , CI , and MCAVmean  but not in arterial pressure. The reduction in MCAVmean correlated to the fall in SVI  and inversely to PPV and SPV . PPV and SPV predicted a ≥15% reduction in MCAVmean and SVI with comparable sensitivity  and specificity . A rapid fluid challenge by tilt-back restored all parameters to baseline values within 1 min.Conclusion: In spontaneously breathing subjects, a reduction in MCAVmean was related to an increase in PPV and SPV during graded CBV depletion and repletion. Specifically, PPV and SPV predicted changes in both SVI and MCAVmean with comparable sensitivity and specificity, however the predictive value is limited in spontaneously breathing subjects. Severe hypovolemia is associated with a critical reduction in central blood volume (CBV) quite often related to hemorrhage or dehydration. This results in hemodynamic instability with a reduction in cardiac output (CO) and tissue oxygen delivery.Volume depletion is usually of acute onset, and neurocardiovascular control mechanisms including reflexes from high and low pressure area receptors initiate the body's defending response  and arterial blood pressure (BP). The experience is, however, that fluid infusion by focusing on these hemodynamic variables allows for wide variation in administered volume because neither BP nor HR accurately reflects changes in CBV  or CO in response to fluid therapy is considered favorable. A meta-analysis of 12 clinical studies showed that with current clinical practice, between 40 and 70% of critically ill patients are so-called responders  and pulse pressure variation (PPV)] are being introduced in clinical medicine as potentially useful tools to guide volume administration  or CO / cardiac index (CI)  with a median (range) age of 25 (23–37) year, height 180 (173–204) cm and weight 72 (62–86) kg, without taking any medication and/or history of regular fainting or cardiac arrhythmia participated in this study. Phase of menstrual cycle in female subjects was not accounted for. This study was approved by the institutional Medical Ethics Committee and took place in the Laboratory for Clinical Cardiovascular Physiology in the Academic Medical Center in Amsterdam. The subjects abstained from heavy physical exercise and caffeinated beverages 4 h prior to the experiment. Diurnal variations in body fluid contents were accounted for by strictly adhering the experiment to the same hour of the day. All procedures and risks associated with the study were explained to the subjects and written informed consents were obtained.Measurements were performed between 11 am and 3 pm in a quiet room with the subjects on a custom built computer controlled tilt table that minimizes muscle tensing and limits vestibular stimulation during tilting   was determined by subtracting critical closing pressure (CCP) from BP at brain level. BP at brain level was estimated by subtracting hydrostatic difference between the finger cuff and the level of transcranial insonation by Transcranial Doppler (TCD) ultrasonography and CCP was estimated by first harmonic Fourier filtered normal arterial pressure and velocity wave heart beat data as described by Aaslid et al. .mean) followed in the proximal segments by means of TCD . The MCA was insonated through the temporal window just above the zygomatic arch at a depth of 40–60 mm with a pulsed 2 MHz probe. After the Doppler signal was optimized, the probe was attached to the skull in a fixed angle by means of a head-band.Regional brain perfusion of the anterior circulation was investigated by the assessment of mean middle cerebral artery (MCA) flow velocity (V2 (PetCO2) was measured using a capnograph . Tidal volume (TV) was calculated by integration of the flow signal. All data were sampled at 200 Hz and collected using an Analog Devices RTI815 PC-card with custom made software. Signals were visually inspected for artifacts and analyzed offline .The HUT induced translocation of CBV to the lower extremities was monitored by electrical impedance plethysmography  measured at the level of the thorax . The gain reflects the effective amplitude dampening of BP fluctuations and phase shift was defined positive where MCAVmean leads MAP at brain level. Coherence examined the strength of the relationship between MAP and MCAVmean  was quantified as the counter-regulatory capacity to maintain MCAVSD. The effect of HUT on measured parameters was assessed using a One Way Repeated Measures Analysis of Variance (ANOVA) test together with the Holm-Sidak method to perform pairwise multiple comparisons. When data were not normally distributed, they are presented as medians and range and non-parametric statistical tests were used.Results are presented as mean ± R2 was calculated according to the following formula:y and f refers to, respectively, the observed and predicted values , CPP, SVI, HR, total peripheral resistance (TPR), PetCO2 and thoracic admittance as the independent variables  in explaining the variance in the dependent variable. Baseline measurements for both the dependent as independent variables were normalized to zero and the effect of tilt was expressed as absolute change with respect to the baseline value.Linear Mixed Model analysis was performed  to examine the relation between brain perfusion (referred to as dependent variable) and hemodynamic and respiratory variables (fixed covariates). mean during progressive CBV depletion related to the resting supine value. A 15% increase in SVI in response to fluid infusion is considered clinically relevant according to previously published criteria  curves evaluated the predictive value of PPV and SPV on volume deficits by determination of sensitivity and specificity values and its corresponding optimal threshold value  with 70 degrees HUT resulting in a 19 ± 11% (p < 0.001) reduction in PP. Although a decrease in CPP was demonstrated during HUT, this was not significantly different from the supine position. SVI , thoracic admittance  and MCAVmean  declined while an increase was seen in HR . CI declined  and TPR increased  only from 0 to 30 degrees without further change at 70 degrees HUT. PPV and SPV did not change from supine to 30 degrees HUT but substantially increased (103 ± 89% (p < 0.05) and 136 ± 117% (p < 0.05), respectively) with 70 degrees HUT. TV and breathing frequency did not change during HUT vs. the supine position while PetCO2 declined  with 70 degrees HUT.Mean arterial pressure and SAP remained constant while DAP increased . Absolute change in PetCO2 was secondly added to this prediction model, resulting in a slightly stronger regression . Single linear plots of the dependent variable (MCAVmean) and its strongest prediction variable (SVI) are shown in Figure mean  and r2 = 0.345 (−0.672–0.998) respectively.Forward stepwise regression analysis revealed that absolute change in MCAVr2 = 0.74, p < 0.0001 and SPV: r2 = 0.76, p < 0.0001) with a higher slope for ΔPPV compared to ΔSPV. Single linear regression analysis was also applied on ΔMCAVmean and ΔPPV or ΔSPV [see panel (B) of Figure mean . The slope of the regression plots for both ΔPPV and ΔSPV were comparable with those between ΔPPV/ ΔSPV and ΔSVI. Again, the highest slope was seen for ΔPPV.Figure mean (right panel) are shown. The AUC values were the highest for PPV and SPV when predicting a decrease in MCAVmean compared to predicting a decrease in SVI (PPV: 0.93 vs. 0.73 and SPV: 0.93 vs. 0.80). The cutoff thresholds and its corresponding sensitivity and specificity values are described in Table mean and SVI with comparable sensitivity  and specificity (94 vs. 89% for both PPV and SPV). In Figure mean.In Figure mean-to-MAP at brain level transfer functions displayed the expected high-pass filter characteristics of dynamic autoregulation, with a decrease in phase lead and increase in normalized gain with increasing sinusoidal tilt frequency  in a fixed body position only, whereas the PaCO2 -to- PetCO2 gradient is enhanced by the postural reduction in CO. This results in an increased VE/Q ratio  is maintained more or less constant in the face of changing CPP (Roy and Sherrington, mean decreased whereas in response to moderate exercise (Brys et al., mean increase together with CBV without changes in PaCO2. In this study, the change in CI from 0 to 30 degrees HUT was limited. From 30 to 70 degrees HUT, SVI and CBV decreased further but CO was maintained, probably attributable to the baroreflex mediated increase in HR. During progressive central hypovolemia a reduction in MCAVmean coincided with the fall in SVI, and vice versa MCAVmean and SVI both increased in response to a simulated fluid challenge by repositioning from upright to supine, supporting a dependency of MCAVmean on CBV. Furthermore, SVI appeared to be the strongest hemodynamic predictor for changes in MCAVmean. Collectively, these findings suggest that in spontaneously breathing volunteers subjected to simulated progressive central hypovolemia, changes in SVI reflect those in MCAVmean in a linear manner (see Figure Cerebral blood flow velocity and its relation with CO has been investigated in several studies. Under conditions of 30 Torr lower body negative pressure (Zhang et al., mean and arterial pressure variations are related too.During surgery or in an intensive care setting, an increase in SVI in response to fluid administration in the anesthetized patient is considered to indicate fluid responsiveness. This study demonstrated an increase in arterial pressure variations in response to a clinical relevant decrease in SVI during HUT and vice versa during tilt back. This strong correlation between SVI and arterial pressure variations is in agreement with earlier research (Hofer et al., Although arterial pressure variations have been proven valuable to predict fluid responsiveness in patients receiving mechanical ventilation, their predictive value in spontaneously breathing patients is lower (Bendjelid and Romand, Potential limitations inherent to the study design should be considered. Transcranial Doppler ultrasonography is used to monitor changes in CBF. This technique has been widely used under the assumption that the cross-sectional area of the MCA is maintained during the measurement. Possible changes in the diameter of the insonated vessel by enhanced sympathetic activity could modulate velocity independently of flow. Previous research showed that increases in sympathetic outflow by baroreflex disengagement or chemoreflex activation do not alter MCA diameter (Serrador et al., Detecting a volume deficit is considered as the major goal of determining fluid responsiveness. However, recent studies indicate that under certain conditions fluid bolus administration is associated with an increased mortality (Maitland et al., mean with comparable sensitivity and specificity, however the predictive value is limited in spontaneously breathing subjects.In summary, the present study shows for the first time in awake humans subjected to progressive central hypovolemia that arterial pressure variations are related to both CBF velocity and SVI. Specifically, PPV and SPV predicted changes in both SVI and MCAVAnne-Sophie G. T. Bronzwaer contributed to the experimental design, data acquisition, data analysis and writing the manuscript. Wim J. Stok contributed to data acquisition, data analysis and manuscript revision. Berend E. Westerhof contributed to the experimental design, data analysis and manuscript revision. Johannes J. van Lieshout supervised the study, contributing to the experimental design, data analysis and writing the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Risk classification and prediction of prognosis in GIST is still a matter of debate. Data on the impact of age and gender as potential confounding factors are limited. Therefore we comprehensively investigated age and gender as independent risk factors for GIST.Two independent patient cohorts  were extracted from the multicentre Ulmer GIST registry including a total of 659 GIST patients retrospectively collected in 18 collaborative German oncological centers. Based on demographic and clinicopathological parameters and a median follow-up time of 4.3 years  disease-specific-survival (DSS), disease-free-survival (DFS) and overall survival (OS) were calculated.GIST patients older than fifty years showed significantly worse DSS compared to younger patients . DSS was significantly more favorable in younger female GIST patients compared with elderly females (p = 0.008). Female gender resulted again in better prognosis in younger patients (p = 0.033).Patient age (<50 years) and female gender were significantly associated with a more favourable prognosis in GIST. Extended studies are warranted to confirm our clinical results and to elucidate underlying pathophysiological mechanisms.The online version of this article (doi:10.1186/s12885-015-1054-y) contains supplementary material, which is available to authorized users. Based on the molecular pathogenesis of driver gain-of-function mutations in c-kit (80-90%) -4 and leth decade  are4% and woHere, we present an observational study, evaluating comprehensively clinicopathological features of GIST and patient outcome to elucidate more deeply the role of patient’s age and gender on the prognosis of GIST. We analyzed 87 GIST patients younger than fifty years (sub-cohort I) and compared these study cohort with data from a single-center collective of patients older than 50 years . Both collectives are part of the multicentre Ulmer GIST registry, encompassing a total of 659 GIST patients at the time of study evaluation.First, our data demonstrate that generally the distribution of gender, tumor localization, histotype, KIT status, mitotic rate, median tumor size and risk classification by different risk scores are similar between patients younger or older than 50 years at time of diagnosis, in concordance with data of large series of GIST patients ,15. MoreThe first most striking result of our study is a significantly more favorable DSS rate after 5 year follow up for patients younger than 50 years in comparison to older patients  -38. CurrIn summary, we present first data on the prognostic impact of age and gender in patients with GIST. The favourable outcome in the young age group which is gender-specific remains currently poorly understood. The real impact of age- and gender-related biological and pathophysiological factors on the prognosis in GIST warrants further prospective studies on larger cohorts with matched genotype and tumor site.


Introduction. The prevalence of hypertension in Africa ranges from 29.7% in Cameroon to 47% in South Africa. Only 10% receive treatment in Cameroon while 32% are on medications in Ghana. Control rates vary from 0.4% to 16.8%. This study was done to assess prevalence, risk factors, awareness, treatment, and control of hypertension in Mafia Island, Tanzania, which has never been documented before, so that necessary interventions can be undertaken accordingly. Methodology. Data was collected through questionnaires and anthropometric measurements were taken. Descriptive statistics were done and potential correlations were analyzed. Results. Out of 570 adults who were included in the study, 154 (27%) were aged 41–50 and the male-to-female ratio was 1 : 1.05. Almost half (49.5%) of the participants fit into the criteria of hypertension. Out of the 118 participants who were aware of having hypertension, 68 (57.6%) were currently taking medication. From those taking medication, only 14 (20.6%) had controlled hypertension. Conclusion. This study tried to show the extent of hypertension and find out risk factors which could explain the high prevalence of hypertension. This is very alarming and a dire need to raise awareness through health education, availability of screening, and treating and follow-up should be given priority. Hypertension is a rapidly emerging disease worldwide and contributes highly to morbidity and mortality. Risk factors not only include obesity, sedentary lifestyle, and age but also genetics and environmental factors contribute to it. Hypertension is usually asymptomatic and the patient presents to the hospital with one of the complications especially in developing countries where very minimal importance and minimal resources are allocated to noncommunicable diseases.A study showed that 80% of deaths that result from noncommunicable diseases occur in the developing world . AnotherIn Cameroon, 29.7% of all participants in a study had hypertension  while itHealth education is extremely vital in health care system, particularly in chronic conditions such as hypertension, which can be prevented, delayed or controlled with the help of medications and lifestyle changes. Developing countries, due to the high burden of infectious diseases, are far behind the ideal health awareness and education in their population. For the government and health care workers to put emphasis on a particular disease or diseases, the burden of that particular disease should be known. This study aimed at providing a baseline so that the governement can allocate its resources according to the need to be able to reduce morbidity and mortality and to improve health of the people.This cross-sectional study was done in Mafia Island, Tanzania. Mafia Island is part of the Tanzanian Spice Islands, together with Unguja and Pemba. According to the 2002 Tanzania census, the population of the Mafia District was 40,801 . The ecoThe study used convenience sampling method and achieved a sample size of 570 nonpregnant adults. An eye and medical camp was organized in Mafia Island in October 2011. This was held at a primary school compound in which there was prior notice to the local people to raise awareness of the medical camp. The questionnaire was filled by medical students, medical personnel, and research assistants whereas measurements were done by medical students and medical personnel only. The information on demographics, smoking habits, alcohol consumption, family history of hypertension, and personal medical history (only diagnosis made by a doctor was considered) including drug treatment was collected by using a questionnaire in Kiswahili. The questionnaires were tested within Dar es Salaam before the research. Participants with high blood pressure were considered to be aware of their status if they answered “yes” to the question “Do you suffer from hypertension?” Treatment of hypertension was defined by the use of blood pressure lowering medications.Blood pressure was measured using aneroid sphygmomanometer (RIESTER brand) while the subject was seated and relaxed with their hand at the level of the heart. People who had eaten food, smoked cigarette, or used alcohol within 30 minutes were asked to rest for 30 minutes before measurements were taken. A standard size of cuff was used.2. Weight was taken using a regular weighing machine after removal of shoes and excess weight in pockets while height was taken using a measuring board resting on the wall. Weight was calculated to nearest 0.5 kg and height to nearest 1 cm.Anthropometric measurements (weight and height) of the sample were taken, body mass index thereafter calculated by using weight (Kg)/height (M)Blood pressure was classified according to the Joint National Committee for hypertension (JNC VII). It was classified as normal blood pressure if systolic blood pressure was between 90 and 119 mmHg and diastolic blood pressure was between 60 and 79 mmHg, prehypertension (mildly elevated) when systolic blood pressure was 120–139 mmHg and diastolic blood pressure was 80–89 mmHg, Stage 1 hypertension (moderately elevated) when systolic blood pressure was between 140 and 159 mmHg and diastolic blood pressure was between 90 and 99 mmHg, and Stage 2 hypertension (severely elevated) when systolic blood pressure was more than 160 mmHg and diastolic blood pressure was more than 100 mmHg [2, normal if it was between 18.5 kg/m2 and 25.0 kg/m2, and overweight if it was from 25.1 kg/m2 to 30 kg/m2. The participants were categorized as obese when body mass index was between 30.1 kg/m2 and 40 kg/m2 and morbidly obese if BMI was more than 40 kg/m2 [Body mass index was categorized according to World Health organization and classified as underweight if BMI < 18.5 kg/m40 kg/m2 .p value was calculated using two-variable Chi-square test. Univariate analysis of variance was also done. Data was entered and processed in SPSS version 17. In this study, p value of ≤ 0.05 was considered to be significant.Descriptive statistics were used to present tables. Data analysis was done from the processed data first by running frequencies, making comparison tables with regard to blood pressure and Permission to conduct the study was obtained from the school of medicine at Muhimbili University of Health and Allied Sciences (MUHAS). Also, permission was sought from responsible authorities in Mafia Island.Twenty-seven percent of the participants were between 41 and 50 years of age. The mean age was 44.53 with standard deviation of 13.92. There were almost equal males and females with 50.9% of them being females and 49.1% being males. The majority (53.3%) of the participants had primary level education while 28.1% had no formal education.Almost a third (32.6%) of the participants had mildly elevated blood pressure and 24.6% had moderately elevated BP while 24.9% of the participants had severely high blood pressure  and hencOut of the 570 participants, 46 (8.1%) were current smokers from which 24 smoke <5 cigarettes a day, 18 smoke between 5 and 15 cigarettes a day, and 4 smoke more than 15 cigarettes a day. A few (6.3%) of the participants consume alcohol. Out of these, 77.8% (28) consume alcohol less than 2 times a week, 16.7% (6) consume alcohol between 2 and 4 times a week, and 5.6% (2) consume alcohol more than 4 times a week.Out of the 118 patients who were aware of having hypertension, only 68 (57.6%) were currently taking medication. The rest were not taking medications mainly due to unavailability of antihypertensives or unaffordability of these drugs . Out of p value 0.21). Compared to the prevalence of hypertension in Africa, that ranges from 29.7% in Cameroon to 47% in South Africa and the studies done in Dar es Salaam and Kilimanjaro in which prevalence of hypertension was shown to be 30% males and 28.6% females, this is alarmingly high. Despite the limitation of few observations, the cut-off of 140 mmHg systolic pressure and 90 mmHg diastolic pressure is still very crucial.In this initial screening, moderate to severe high blood pressure was seen among 49.5% of the participants. In males, high blood pressure was seen among 52.1% (146) participants while in females it was at 46.9% (136) though this was not statistically significant . This fact can be reflected by a very high percentage (73.3%) of the participants who did not know if they had hypertension or not (they had never measured). This was particularly disturbing since male and female participants were almost equal and monitoring blood pressure in pregnant women is mandatory. Two-thirds (194 of the 290) of the women had never got their blood pressure measured.The reason behind this alarming prevalence could be not only the sedentary lifestyle in Mafia Island, diet that includes large amount of salt and fish, but also the low level of education and poor and substandard health facilities. In analyzing the relation between high blood pressure and level of education, it was very significant .Participants who were underweight had prevalence of high blood pressure at 15.4% while those who had normal BMI had high blood pressure prevalence of 40.2%. Hypertension was seen in 56.2% of overweight people and 65.3% of obese participants. All morbidly obese individuals had high blood pressure. The relation between BMI and high blood pressure was also very significant . High blood pressure was seen among 26.1% of smokers and 51.5% of nonsmokers. The relation between smoking and high blood pressure was very significant . The blood pressure was elevated in 49.9% of people who used alcohol and 49.3% of those who did not use alcohol. This was not significant . There was also positive corelation between family history and high blood pressure . The reason of participants being unaware would be a wide variety: from ignorance, not having right information, poor health care seeking behaviors, and unavailability of resources.High blood pressure was almost only (95%) seen in participants above 31 years. Analysis showed there was very significant relation between age and high blood pressure . This can also be explained by poor adherence to medications or irregular intake. The potential of myocardial infarction, stroke, and poor quality of life reflected from this statistics is very high. Other contributing factors may be lack of physical activity, unhealthy diet, poor awareness, and suboptimal facilities. In verbal discussions with the participants, it was noted that in Mafia there were significant number of adults with stroke but they were treated at home with alternative medications.Out of these 118 patients who were aware of having hypertension, 68 (57.6%) were currently taking medication. This was very high compared to the study that showed 10% receive treatment in Cameroon while 32% are on medications in Ghana and also the Dar es Salaam study that showed approximately 10% reported receiving treatment. Out of the 118 participants who were aware of having hypertension, only 34 (28.8%) had controlled blood pressure (systolic blood pressure < 140 mmHg and diastolic blood pressure less than 90 mmHg). Twenty-four (20.3%) had systolic blood pressure between 140 and 160 mmHg and diastolic blood pressure between 90 and 99 mmHg while 50.8% had severely high blood pressure (systolic pressure > 160 mmHg and diastolic pressure more than 100 mmHg). This may be due to various reasons, among which the most likely would be unavailability of medications which was a complaint that was very often received during the research data collection. Noncompliance of the medicines could also contribute to the poor control and this can be associated with level of education. Out of those hypertensives using medications, only 20.7% had optimal and controlled blood pressure whilst the majority (79.3%) had uncontrolled blood pressure. In comparison, 60% of hypertensives who were not taking medications regularly had controlled blood pressure. However, this was statistically insignificant (Participants were those who attended the eye and medical camp that was well publicized. Only patients who could come by themselves were included in the study, while those sick and debilitated people could not make it. Therefore, those with complications of hypertension and diabetes mellitus were not included; thus, there was selection bias. It remains, however, that participants in the study could still differ from the general population by being more or less health conscious and having less severe disease, for example, which could affect some parameters in the study.The study used a cross-sectional design, which precludes any causality inference.Diagnosis of hypertension was based on blood pressure measurements during a single encounter, which is variant with guidelines recommendations for hypertension diagnosis using two measurements recorded on three separate occasions . This maThe strengths of this study include the large sample of the general population and the rigorous collection of various lifestyle factors, medical data, and blood pressure measurements by trained medical personnel according to standardized protocols. In addition, our sampling approach provides evidence that simple announcements through mass media can attract from the community a large number of individuals at risk of undiagnosed hypertension.In this survey in Mafia Island, almost half of the participants had moderate to severe hypertension, most of whom were unrecognized. Together with that, those who were aware of their disease were also assessed for control of the situation and this study showed their control was not adequate. This is very alarming and therefore shows a need to raise awareness and availability of screening, treating, and follow-up. Furthermore, this study can act as a baseline for more studies to be undertaken and more evidence to be gathered.


Several studies suggest that there is a pathogenic link between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases. On the other hand, increased sympathetic tone has been described in several respiratory diseases. Our objective was to determine whether hypertension mediated by sympathetic overactivity is a mechanism that explains the association between COPD and cardiovascular diseases.Prospective nested case-control observational study; 67 COPD patients were matched 1:1 by sex and age to controls with smoking history. 24 hour-blood pressure monitoring, urinary catecholamines and their metabolites measurement, echocardiography, carotid ultrasound examination, nocturnal oximetry and retinography were performed.classic cardiovascular risk factors and comorbidities were similarly distributed between cases and controls. No significant differences for blood pressure variables  or catecholamines values were found between both groups. There was a tendency for lower left ventricle ejection fraction in the COPD cases, that approached statistical significance . There were no differences in the retinal arteriovenous ratio, the carotid intima-media thickness, or the number of carotid plaques, between cases and controls. Fibrinogen values were higher in the COPD group  and mean nocturnal oxygen saturation values were lower for COPD patients .Hypertension induced by sympathetic overactivity does not seem to be a mechanism that could explain the association between COPD and cardiovascular disease. Observa in 2030 . However in 2030 ,6. UnderAtherosclerosis is associated with an increased risk of stroke, coronary artery disease, peripheral arterial disease and mortality , but othOur main objective was to assess if BP in patients with COPD has a different profile than in matched controls with a history of smoking and if the differences might be related to sympathetic tone. That would suggest a pathogenic link between COPD and CVD. The secondary objectives of our study , were to evaluate if hypertensive organ damage was different in COPD cases.This is a prospective, 1:1 matched, case-control observational, non-interventional study. The study included men and women with a history of smoking. Subjects were invited to participate when they attended either their primary care clinic , or the internal medicine clinic, the respiratory clinic or the tobacco cessation program of our hospital . The rec1/FVC ratio < 0·70 in post-bronchodilator spirometry. Each COPD subject was matched 1-to-1 for sex and age with one control subject with normal spirometry. Age was matched via nearest neighbor matching with a maximum allowable difference of 5 years between two participants. COPD subjects for whom no control case was found within the allowed limits were left unmatched and excluded from analysis.Inclusion criteria were: smoking history with a pack-years index > 10, and age > 40 years. Exclusion criteria were: uncontrolled neoplasm, diagnosis of other inflammatory diseases (e.g.: collagen vascular diseases), known respiratory diseases other than COPD, morbid obesity, pregnancy, spirometry that was neither normal nor obstructive, and refusal or incapacity to give informed consent. A COPD case was defined by a FEVMedical information was obtained through a questionnaire, which included demographic background, socioeconomic status, life habits and medical history. Dyspnea was evaluated with the modified medical research council (mMRC) scale. Comorbidity was assessed by means of the non-age adjusted Charlson index . To compThe study was performed in accordance with the 1964 Declaration of Helsinki and its later amendments and it was approved by our ethical committee . Informed written consent was obtained from all the subjects.Spirometry was performed according to the American Thoracic Society/European Respiratory Society consensus guidelines , and usiTwenty-four hour BP monitoring was performed with Spacelabs 90207 . The non-dominant arm was used for measurement. Patients were instructed to maintain their usual activities, avoiding strenuous exercise. The monitors were programmed to obtain BP readings every 20 minutes between 8:00 h and 22:00 h and every 30 minutes between 22:00 h and 8:00 h. Daytime ambulatory BP was defined as the period between 8:00 and 22:00 h and nighttime as the period between 22:00 and 8:00 h. We classified the patients by nocturnal systolic BP fall as follows: extreme-dippers if the fall was ≥ 20%, dippers if the fall was ≥ 10% but < 20%, non-dippers if it was ≥ 0% but < 10% and risers if it was < 0% .Venous blood was obtained in the morning and after an overnight fast. In order to reduce possible influence of daytime activity on the excretion of catecholamines, urine was collected for 12-hours, starting in the evening, after discarding the first voided sample . UrinaryEchocardiographies were performed by a cardiologist blinded to the clinical information, using a Philips IE33  ultrasound imaging system with a S4 transducer. M-mode, two-dimensional, Doppler (continuous and pulsed wave), and color Doppler were performed. Left ventricle (LV) systolic function was assessed in most cases by Teichholz method and Simpsons’s biplane method. In some cases, it was assessed by visual estimation. LV systolic depression was defined as left LV ejection fraction < 50%. Right ventricle (RV) dilatation was defined as end-diastolic diameter > 30 mm or right-to-left ventricular end-diastolic diameter ratio ≥ 1 in apical 4-chamber view. Systolic pulmonary artery pressure (SPAP) was derived from the right atrioventricular pressure gradient using peak velocity of tricuspid flow regurgitation with continuous wave Doppler in the apical four chamber view and the modified Bernoulli equation . Right aTwenty to 30 min. after pupil dilation with 2 drops of tropicamide and phenylephrine, an eye fundus photograph centered on the papilla, and covering an angle of 50°, was taken with a digital fundus camera equipped with a 540 nm filter and connected to an Imagenet I-base system . A previously validated computer system was used to measure the calibers of retinal blood vessel, as described elsewhere . The proWe used high-resolution B-mode ultrasound, Philips IE33 , with a 10-MHz linear transducer. Carotid intima-media thickness (IMT) was measured at the far wall of the right and left common carotid arteries, 10 mm from the carotid bifurcation, over the proximal 10 mm long segment. IMT was determined using an automatic software C-IMT in Qlab system. The final IMT was the largest average IMT (left or right). The plaque criteria in the accessible extracranial carotid tree were defined according to Mannheim consensus . The exa2) was measured with a finger pulse oximeter . The mean nighttime SpO2 (MNSpO2), percentage of recording time with SpO2 <90% (CT90) and the number of dips in SpO2 ≥4% per hour of recording time (DI4), were calculated using computer software .Nocturnal oxygen saturation  compared the main characteristics of those case matched with controls and those lost to matching process and (2nd) performed multiple regression analysis by means of a stepwise forward selection using systolic BP as the dependent variable. We ruled out multicollinearity checking the variance inflation factor values and we used an automatic weighted regression procedure to take into account heteroscedasticity [Normal distribution of data was assessed using the D’Agostino-Pearson test. Between-groups comparisons for continuous variables were made using the nd 10·18 . A samplnd 10·18 . We tookasticity .1 was ≥ 80% for 11 COPD cases, 79–50% for 30, 40–30% for 22, and < 30% for 4 cases. Five subjects refused to participate in the study. Two hundred and seven patients  accepted to participate. Of this number, 67 COPD cases could be matched with 67 controls, and were included in the analysis . FEV1 waBP monitoring results are summarized in We repeated the analysis including only patients without previous treatment for hypertension, with similar results  were performed, because of technical problems with the equipment. In order to rule out significant bias, we compared the characteristics of those subjects in which oximetry was performed with those in which it was not possible. No differences were found, except for a slightly higher FVC in COPD cases in which oximetry was performed  cases and 8 (11·9%) controls (p = 0·34). When we analyzed the valid retinograhies, we did not find significant differences between cases (AVR: 0·8487 ± 0·0822) and controls .Table F in In this study we have investigated a possible mechanism for the link between COPD and CVD: hypertension induced by sympathetic overactivity. However, we have not found differences in BP or catecholamines values between patients with COPD and matched controls.CVD are a major contributor to mortality in COPD. Actually, COPD might be an independent risk factor for CVD–4,24–26.Proposed mechanisms for the association between CVD and COPD include systemic inflammation, hypoxia, oxidative stress, connective tissue alteration, augmented platelet activation and impaired endothelial function . SympathIf sympathetic overactivity would be present in COPD, possible consequences would include endothelial dysfunction, arterial stiffness, left ventricular hypertrophy (LVH), arrhythmias and hypertension . Few stuWe must recognize the fact that catecholamines measurement might be relatively insensitive to detect sympathetic overactivity. Monoamines excretion is susceptible to daily variations within subjects . Also, tA secondary objective of our study was to search for differences suggestive of hypertensive organ damage between cases and controls. Anderson et al previously found LVH in 30·1% of normoxemic COPD patients . EchocarHypertensive retinopathy has been regarded as a marker of systemic vascular disease . Retinal1 < 30%), and this is a relevant limitation. However, CVD incidence is high in all stages of COPD, and death due to CVD is frequent in both mild and moderate COPD patients [Several limitations of our study must be considered. The most important are its single-center nature and relatively small sample size, which limit the generalisability of the results. The control subjects had a lesser degree of tobacco exposure than the COPD patients, but this could have plausibly biased the results towards higher BP values in the COPD group. The absence of differences between both groups cannot be attributed to this fact. We must emphasize the fact that the control group cannot be considered healthy, given the history of smoking. Our intention when we decided to study subjects with a history of smoking was to avoid the confusing factor of tobacco. However, it is plausible that the inclusion of an additional control group of age- and sex-matched subjects who did not smoke might had revealed differences with respect to COPD cases. The heterogeneity in disease severity between the COPD cases is also a limitation. There were relatively few cases with mild COPD and few patients with very severe airway obstruction Click here for additional data file.


CST3 expression. Genetic analysis revealed a significant association of blood uric acid (BUA) and BCr in CEN with F1 but not with F1SP, suggesting they may be heritable traits. Taken together, our results suggest serum lipids, kidney function and especially diastolic pressure rather than systolic pressure were improved in CEN or their offspring, suggesting these factors may play an important role in familial longevity.Centenarians are a good healthy aging model. Interestingly, centenarians’ offspring are prone to achieve longevity. Here we recruited 60 longevity families and investigated the blood biochemical indexes of family members to seek candidate factors associated with familial longevity. First, associations of blood indexes with age were tested. Second, associations of blood parameters in centenarians (CEN) with their first generation of offspring (F1) and F1 spouses (F1SP) were analyzed. Third, genes involved in regulating target factors were investigated. We found that total cholesterol (TC) and triglyceride (TG) increased with age (20–80 years), but decreased in CEN. Similarly, blood urea nitrogen (BUN) and blood creatinine (BCr) increased with age (20–80 years), but were maintained on a plateau in CEN. Importantly, we first revealed dual changes in blood pressure, i.e., decreased diastolic blood pressure but increased systolic blood pressure in CEN, which associated with altered  Centenarians live to or beyond the age of 100 years, surpassing the current human life expectancy with about 20–25 years. Several cross-sectional and follow-up studies investigated the centenarians and revealed that they usually manage to escape or delay major age-related diseases, especially those with high morbidity and mortality, such as cardiovascular disease, neurodegeneration and cancers1233567810We previously investigated 535 centenarians and identified some protective or detrimental risk variants14Last year, we managed to recruit 60 longevity families from Hainan province, a well-known longevity region in China, and performed a complete physical examination on all subjects. Based on this population, we found that the thyroid function was associated with longevity and could be heritable60 longevity families  consisting of 61 centenarians, 63 first generation of offspring (F1), 47 spouses of F1 (F1SP), 25 second generation of offspring (F2) and 10 spouses of F2 (F2SP) were recruited from Hainan province of China in July, 2014. The average ages are 102.70, 62.23, 59.90, 31.87, and 31.11 years, respectively. All subjects are the Han nationality. Of them, 40 families were available to test the genetic correlations of blood biochemical indexes.All subjects were invited to participate in a physical examination. Clinical biochemical parameters including total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglyceride (TG), blood glucose (BG), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free T3, free T4, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin, globulin, total bilirubin, direct bilirubin, indirect bilirubin, blood urea nitrogen (BUN), blood uric acid (BUA) and blood creatinine (BCr) were determined following standard laboratory procedures. Blood pressure was measured using a standard mercury sphygmomanometer on the right arm after at least 10 min of rest. History of severe diseases in cardiovascular, pulmonary, digestive, urinary, and nervous systems was recorded according to centenarian self- or their family-reporting data. The study protocol was approved by the Ethics Committee at Kunming Institute of Zoology, Chinese Academy of Sciences. Written informed consent was obtained from each of the participants. All methods were carried out in “accordance” with the approved guidelines.63 samples consisting of 27 centenarians, 18 F1 and 18 F1SP were selected to perform RNA-sequencing (RNA-seq). Total RNA was isolated from 3 mL of fresh blood using the Trizol reagent (Invitrogen). The RNA-seq was performed at the Beijing Genomics Institute at Shenzhen according to the manufacturer’s protocol. To estimate the level of gene expression, the reads count was transformed into fragments per kilo bases per million mapped reads (FPKM)http://www.ncbi.nlm.nih.gov/), Genecards (http://www.genecards.org/) and Genome-Wide Association Studies (GWAS) Catalog (http://www.genome.gov/gwastudies/) databases and collected related genes. Genes involved in lipid metabolism were retrieved from the Transcription Regulatory Regions Database .For those candidate blood indexes, we systematically searched the National Center for Biotechnology Information , in which the P value was adjusted by the Benjamini-Hochberg (BH) method, belonging to the False Discovery Rate (FDR) for correction. The rest data were analyzed using Graphpad Prism 5.0 . The associations of blood parameters with age were analyzed using the Pearson relation. Levels of blood parameters between the CEN and the old group (aged 60–80 years) were compared using the Student’s t test. Genetic additive effect (narrow sense) which was measured as the covariance (the slope) of the relationship between centenarians and F1 as well as F1SP was determined according to the method as describedBlood biochemical indexes among the CEN, F1, F1SP, F2 and F2SP groups were analyzed by One-way ANOVA using SPSS software (13.0). When the main effects were significant, means were compared using the Bonferroni post hoc test. Gene expression was analyzed using the DESeq2 package  to seek potential heritable parameters between CEN and F1. As a result, BUA and BCr, two important indicators for kidney function, in CEN were significantly and positively related to that in F1SP , NR1D1 (p = 1.42 × 10−5), PLCG1 (p = 1.48 × 10−5), TPI1 (p = 2.89 × 10−3), DBI (p = 6.91 × 10−3), AGPAT2 (p = 1.12 × 10−2), PLTP (p = 6.69 × 10−2), HMGCR (p = 8.56 × 10−2), FABP6 (p = 0.019), DGAT1 (p = 0.028) and NR1H3 (p = 0.029) in CEN were expressed differently from that in F1SP (MSR1 (p = 1.05 × 10−3), NR1D1 (p = 7.5 × 10−3), PLCG1 (p = 7.76 × 10−3), TPI1 (p = 6.13 × 10−3), DBI (p = 0.011), AGPAT2 (p = 0.015) and PLTP (p = 0.049) remained significant, but the HMGCR (p = 0.057), FABP6 (p = 0.095), DGAT1 (p = 0.119) and NR1H3 (p = 0.122) were not significant  in CEN compared to the old subjects aged 60–80 years. We wondered how they were regulated. Among the genes involved in lipid metabolism, the  in F1SP . After anificant . There wCST3 (p = 2.7 × 10−10), NR3C2 (p = 1.41 × 10−7), COMT (p = 4.0 × 10−7), NAGLU (p = 2.49 × 10−3), RENBP (p = 4.72 × 10−3), NPR2 (p = 1.29 × 10−2), DBH (p = 1.54 × 10−2), CYBA (p = 1.77 × 10−2), NOS3 (p = 3.29 × 10−2), ADRBK1 (p = 5.77 × 10−2), NPPA (p = 6.09 × 10−2), LCAT (p = 0.014), TNFRSF1B (p = 0.017), NPR3 (p = 0.019), NEDD4L (p = 0.027), F2R (p = 0.037) and GSR (p = 0.043) between the CEN and F1SP. After adjustment, the CST3 (p = 1.29 × 10−7), NR3C2 (p = 2.14 × 10−5), COMT (p = 4.76 × 10−5), NAGLU (p = 5.61 × 10−2), RENBP (p = 8.52 × 10−2), NPR2 (p = 0.017), DBH (p = 0.019), CYBA (p = 0.021), NOS3 (p = 0.031), ADRBK1 (p = 0.044) and NPPA (p = 0.046) remained significant. However, the rest of above genes were not significant , which however, were not significant after the BH adjustment , DIP2C (0.031) and ASL (p = 0.032) was different between the F1 and F1SP, which were not significant after the BH adjustment  were upregulated while some  were downregulated in CEN versus F1SP. Based on their known functions, they may confer both beneficial and detrimental effect on regulating lipid profiles, suggesting there is a balance in the regulation of the lipid metabolism in the longevity subjects. However, the overall outcome seemed to reduce lipid levels and thus accounted for the favorable lipid profile in centenarians. Of course, there exist many other influential factors that may explain the favorable lipid level in CEN, such as hormone regulation22202425In this study, using association and further comparison analyses we identified several blood parameters that may contribute to longevity. First, TC and TG increased with age until 80 years, but decreased in centenarians, indicating that lipid metabolism was improved in the oldest old. A similar trend was observed for LDL-C, although it was not associated with age before 80 years. The changes in lipid levels were consistent with that in other studies19CST3 gene, it has the most significant difference between the CEN and F1SP, and it codes a protein called cystatin c which has been positively associated with systolic pressure but inversely with diastolic pressure in the 24 h ambulatory blood pressure monitoring31LRRC16A, DIP2C and SLC28A2, were differentially expressed between CEN and F1SP, being likely involved in the maintenance of kidney function3335More importantly, we observed for the first time that diastolic blood pressure rather than systolic pressure was improved in CEN compared to the elderly. Blood pressure is a well accepted cause for age-related diseases, not only for the cardiovascular disease, but also for cerebrovascular and/or neurodegenerative diseases, such as cerebral hemorrhage and senile dementia28LRRC16A and ARG1 in CEN were highly associated with that in F1, but not F1SP, being the candidate genes for the inheritance.Longevity is an extreme phenotype of aging. CEN manage to live to or over 100 years of age, their descendants are prone to achieve longevity, suggesting the possible involvement of genetic factors. In our previous studies, we identified some protective or risk mutations in CEN1414In summary, our results revealed that the improvements of serum lipids, kidney function, and especially the diastolic blood pressure but not systolic blood pressure as beneficial factors for longevity. Of them, improved kidney function may be a heritable phenotype that could explain the lower prevalence of age-related diseases to some extent in both CEN and their descendants.How to cite this article: He, Y.-H. et al. Improved lipids, diastolic pressure and kidney function are potential contributors to familial longevity: a study on 60 Chinese centenarian families. Sci. Rep.6, 21962; doi: 10.1038/srep21962 (2016).


To assess the validity of self-reported weight, height, body mass index (BMI), waist circumference and blood pressure compared with standardized clinical measurements and to determine the classification accuracy in overweight/obesity and central adiposity.This pilot study was integrated into a life-course study entitled “Hong Kong Women's Health Study” among 1,253 female nurses in Hong Kong who were aged 35 years to 65 years. Data were collected from self-administered questionnaires that were mailed to the respondents. Of these participants, we obtained the standard body measurements of 144 (11.5%) at our research center. We then compared the self-reported anthropometric variables and blood pressure with the measured data to assess validity based on the level of misreporting, percentage of agreement, consistency, sensitivity and specificity.The self-reported and measured values were highly correlated in terms of anthropometry and blood pressure (correlation coefficients ranged from 0.72 to 0.96). Height was overestimated at an average of 0.42 cm, and waist circumference was underestimated at 2.33 cm (both P<0.05), while no significant differences were observed from weight, blood pressure and BMI . The proportions of overweight, obesity, and central adiposity by self-reported data did not vary greatly from the measured data . The self-reporting resulted in correct classifications of BMI, waist circumference, and systolic blood pressure in 85%, 78%, and 87% of women, with corresponding Kappa index values of 0.79, 0.55, and 0.82, respectively. Sensitivity and specificity were 84.6% and 95.7%, respectively, with respect to overweight/obesity detection, whereas those for central adiposity detection were 70.6% and 83.8%, respectively.In a sample of female Hong Kong nurses, the self-reported measures of height, weight, BMI, waist circumference and blood pressure were generally valid. Furthermore, the classification accuracies of overweight/obesity and central adiposity were acceptable. They represent the physical characteristics of a person and reflect the biological, genetic, and environmental characteristics of a population. The body mass index  and later life health outcomes . The present validation study was integrated into the Hong Kong Women's Health Study as a pilot study. The study population was composed of female Chinese nurses in Hong Kong who were aged 35 years to 65 years. The Association of Hong Kong Nursing Staff helped with the systematic sampling of total 8320 eligible nurses from their membership database. Packages were mailed to the home addresses of the selected nurses, and these packages contained a questionnaire, an informed consent form, an introduction leaflet with a reply slip, a paper tape measure, and a pre-paid return envelope Finally, 1,253 nurses who returned valid questionnaires were recruited. To validate the self-reported anthropometrics and blood pressure in the questionnaire, we asked the potential responders whether they wanted to participate in the scheduled face-to-face body measurement described in the mailed survey. Those who were willing could tick the corresponding box in the reply slip and return it together with the questionnaire. Once we received the valid reply slips, we contacted the participants through telephone or/and email immediately and invited them to visit our research center for taking body measurements within one month. This minimized time duration prevented anthropometric variations as a result of a long delay in between the gathering of self-reported values and the measurements. The study protocol was approved by the Research Ethics Committee of the Chinese University of Hong Kong. A signed statement of informed consent was obtained from each participant.Regarding to the self-reported anthropometrics and blood pressure, participants were asked to measure and record the value according to the written instructions. The height and waist circumference could be reported in either centimeter or inch, and the weight could be reported in either pounds or kilograms. All data were converted to metric units (meter or kilogram) for analysis. The guideline for measuring waist circumference was printed on the introduction leaflet. Participants were required to use the complimentary paper tape measure to measure their waist circumference. For the blood pressure, a note was printed in the questionnaire that reminded them to provide the value from the most recent body check. If a sphygmomanometer was available, they were asked to measure their blood pressure at least twice, with the help of other professional person, and write down the mean blood pressure on the questionnaire.The face-to-face measurement procedures for all anthropometrics were based on standard protocols. All measurements were conducted by the investigator and a trained research assistant. Height was measured to the nearest 0.1 cm by a stadiometer. First, we confirmed that the surface on which the scale was placed was horizontal and made adjustments to ensure that the upper part of the measuring rod was straight and vertical. Prior to measurement, participants were required to remove hair ornaments, shoes, and heavy outer garments. They were then advised to stand straight and look straight ahead. Their backs were pressed to the height rule, with their shoulders and arms drooping naturally. Furthermore, they were requested to keep their feet together. The research assistant ensured that the backs of the heads, backs, buttocks, calves, and heels of the participants were touching the rule. The slide of the measuring rod was gradually lowered until the hairs of the participants were flattened and the rule could not move any further. The investigator then wrote down the readings.2).A standardized weighing scale was used to measure body weight to the nearest 0.1 kg. This scale was also placed on a horizontal hard-floor surface. Prior to measurements, participants removed heavy outer garments such as jackets, coats, skirts, shoes, socks, hats, watches, necklaces, and other carry-on items. They then stood at the center of the machine platform to prevent the unbalanced distribution of weight between the two feet. Weight was then recorded when the arrow no longer wiggled and was aligned steadily. BMI was then calculated as weight in kilograms divided by the square of height in meters  by the observer using a mercury sphygmomanometer and an appropriately sized cuff. Participants who were currently taking anti-hypertension medicine were asked to not take it before coming to the center for body measurements. Measurements were taken while the participants were seated and given at least five minutes of rest. The right arms of the participants were positioned on a table, with their palms up at chest height. Every participant was measured twice, and the mean of two measurements was computed. If the two measurements varied by >20 mmHg, a third measurement was conducted and the mean of two similar measured values was calculated. If participants were found to have elevated blood pressure levels (diastolic ≥90 mmHg or systolic ≥140 mmHg), they were asked to remain at rest for at least another five minutes before the second and third readings were taken. The mean of the two lower measurements was then computed. Hypertension was defined as either a systolic blood pressure of ≥140 mmHg or a diastolic blood pressure of ≥90 mmHg t-test for continuous variables and chi-square tests for nominal and ordinal variables. The mean differences between the measured variables and self-reported variables were investigated by paired-samples t-tests. The degree of correlation was measured by Pearson correlation analysis. BMI and waist circumference were used to identify obese subjects among participants. The BMI results were divided into four categories: underweight (<18.5 kg/m2), normal weight (18.5 kg/m2–<23.0 kg/m2), overweight (23.0 kg/m2–<25.0 kg/m2), and obese (≥25.0 kg/m2) Data were presented as mean (standard deviation) or proportion as appropriate. To verify the representativeness of the participants in validity examinations, we examined the differences in demographic characteristics and key variables between subjects who participated in the validity examination and the total sample by a one-sample A total of 216 nurses were willing to participate in the body check, and 144 nurses  successfully completed the face-to-face body measurements . The demOur study indicated that middle-aged female nurses in Hong Kong could accurately report their weight and blood pressure values but that they underestimated waist circumference and overestimated height. These biases from self-reported values resulted in a slight misclassification of overweight/obesity and central adiposity. Nonetheless, the overall agreements with respect to the reporting of accurate values were reliable and acceptable.et al.Our findings are consistent with those of previous studies In our study, the accuracy of self-reported blood pressure was also acceptable. The mean differences between measured and self-reported values were slight, which is consistent with the Harvard Nurses' Health Study Some limitations of the present study must be addressed. First, the relatively small sample size for validation may lower the study power and representativeness. In addition, the nurse sample may limit the generalizability of the results. Second, due to the limited manpower and material resources, we did not control for the circadian variation in blood pressure measurement, which could present a possible confounding effect on the measurement bias. But we suggest that it unlikely to substantially affect the overall results, because it was random error when the time frame for self-measurement was no limit. Third, we recruited the study subjects through convenience sampling in the validity examination, only those who indicated their willingness to participate were included. Hence, selection bias may be present to some extent because the behavior decisions of a person may vary with social-demographical status. Our results also indicated that the validation sample was older, heavier, and less educated than the total sample. Despite of these differences, the two samples did not differ significantly in terms of other key variables. Several studies Despite these limitations, no comparable studies have been conducted in Hong Kong adult populations to our knowledge. We found that female nurses in Hong Kong reported their height, weight, and waist circumference more accurately than the participants in some occidental studies. This higher accuracy may be ascribed to the professional medical background of the nurses in our study population and to the personality or cultural characteristics of Hong Kong women. A similar finding was reported in Japan Supplementary S1Data of the 144 subjects who participated in the face-to-face body measurement.(SAV)Click here for additional data file.


In case of intravascular fluid depletion, large veins react to volume expansion with dilation. Little is known about the reaction of arterial vessels. We herein report on the effect of a standardized fluid bolus on the diameter of the common carotid artery (CCA) and its association with hemodynamic parameters, assessed in 20 mechanically ventilated patients after cardiac surgery. CCA was visualized using ultrasound, and the percentage increase in diastolic diameter was calculated by measuring before and after administration of crystalloid infusion solution. Invasive arterial blood pressure and pulse pressure variation (PPV) were assessed in parallel.1–Q3: 5.4–7.1) mm, and it significantly increased to 6.7 (5.8–7.3) mm upon fluid administration [5.0 (1.9–10.5) % increase]. Mean arterial blood (MAP) pressure likewise increased from 68 (70–73) to 85 (71–100) mmHg, whereas PPV was significantly reduced from 17.6 (16.8–23.9) to 13.2 (6.7–18.1) %. There was a significant association between the change in CCA diameter and the hemodynamic response . Furthermore, carotid diameter measured before volume expansion significantly correlated with the delta-PPV upon fluid administration .Median diastolic CCA diameter was 6.2 (QDiameter of the CCA increases in response to intravascular volume expansion. Additional studies on the interplay between carotid geometry and intravascular fluid status are necessary. In recent years, bedside ultrasound has become an important tool for the simple and non-invasive hemodynamic assessment of critically ill patients History of radiotherapy or surgery of neck regionBilaterally inserted venous catheters (jugular or subclavian vein)Spontaneous breathing activityThis observation was conducted at the cardiac-surgery intensive care unit (ICU) of the University Hospital Bonn, Germany, after approval by the Institutional Review Board . In accordance with the judgment of the IRB, all measurements were considered part of routine practice and so, informed consent was waived. All patients age more than 18 years arriving at the ICU after elective cardiac surgery using heart–lung machine were screened for the following exclusion criteria:T 8 ml/kg BW, Ppeak ≤ 25 cm H2O, 10 cm H2O ≤ positive end-expiratory pressure (PEEP) ≤ 13 cm H2O, average I:E ratio 1:1.5 , SaO2 ≥ 95 %, PaCO2 ≤ 45 mmHg]. Sonographic measurement of the CCA was performed using a Philips HD15 ultrasound device , equipped with a linear transducer . By default, patients arriving at the ICU after cardiac surgery had received a central venous catheter preoperatively, usually inserted into the right internal jugular vein. To avoid any risk of infection at the puncture site, sonographic measurements were conducted on the contralateral side only, usually on the left. All sonographic images were obtained by two board-certified anesthesiologists, each with experience of more than 100 ultrasound-guided central venous cannulations. The hemodynamic data were collected by another investigator, blinded for the results of sonography. Ultrasound examinations and collection of hemodynamic data were performed with the patient in supine position with the head of bed 30° elevated (semi-recumbent). CCA was visualized by placing the ultrasound transducer perpendicular to the skin in a transverse plane on the patient’s neck lateral to the cricoid cartilage (short axis view). The artery was identified by compression as well as by color Doppler imaging. To avoid any influence of external compression on the CCA diameter during the following examination, sufficient ultrasound gel was used to allow the transducer to lose direct skin contact, thus applying the least possible amount of pressure. A B-Mode scan was recorded simultaneously with the electrocardiogram, the image was frozen at end-expiration, and the diastolic antero-posterior diameter of the CCA was measured in centimeters from intimal to intimal edge within the frozen B-Mode image. The procedure was repeated two times, and the mean diastolic CCA diameter was calculated from these three measurements. Thereupon, the transducer was removed and its location was marked on the skin.All patients were clinically assessed by a blinded ICU consultant. Only patients being supposed to be volume demanding [based on clinical signs of inadequate tissue perfusion ] were included into the observation. At the ICU, patients were sedated using propofol and sufentanil and controlled mechanically ventilated  − 100. Furthermore, delta-MAP, defined as increase in MAP upon fluid expansion, and delta-PPV, defined as reduction of PPV, were calculated.After the initial assessment, a crystalloid infusion solution  was administered (30 ml/min). Immediately after a total infusion volume of 7 ml/kg BW was reached, ultrasound measurement was repeated. Between these sequential measurements, neither patient position, nor ventilation parameters, nor infusion rate of vasoactive drugs were changed. The percentage increase in CCA diameter was calculated using the formula: , whereas PPV was significantly reduced to 13.2 (6.7–18.1) % (p < 0.001).CCA was visible and easily identifiable in all patients. The percentage CV values, revealing high intra- as well as inter-observer reliability, were as follows: assessment 1: 12.93; assessment 2: 14.37; observer 1: 14.4; observer 2: 12.91. Median diastolic CCA diameter measured from intima to intima was 6.2 (5.4–7.1) mm prior to volume expansion  population, revealing significant associations using non-parametric tests. Of course, future studies should be performed on a larger collective. Third, repeated sonographic measurement of CCA diameter was performed by the same investigator as the initial assessment and was thus not truly blinded in this aspect. Last, although carotid diameter was not associated with the patients’ body dimensions, due to the close dependency of CCA diameter and delta-PPV, it may be hard to rule out any patient-related confounding factors on the CCA diameter measurement.Our results suggest that the diameter of the CCA responds to intravascular volume expansion with significant dilation in patients clinically appearing fluid demanding. Additional studies including invasive hemodynamic monitoring should shed more light on the interplay between carotid geometry and intravascular fluid status.


Objective To assess whether using intensive blood pressure targets leads to lower blood pressure in a community population of people with prevalent cerebrovascular disease.Design Open label randomised controlled trial.Setting 99 general practices in England, with participants recruited in 2009-11.Participants People with a history of stroke or transient ischaemic attack whose systolic blood pressure was 125 mm Hg or above.Interventions Intensive systolic blood pressure target (<130 mm Hg or 10 mm Hg reduction from baseline if this was <140 mm Hg) or standard target (<140 mm Hg). Apart from the different target, patients in both arms were actively managed in the same way with regular reviews by the primary care team.Main outcome measure Change in systolic blood pressure between baseline and 12 months.Results 529 patients (mean age 72) were enrolled, 266 to the intensive target arm and 263 to the standard target arm, of whom 379 were included in the primary analysis (182 (68%) intensive arm; 197 (75%) standard arm). 84 patients withdrew from the study during the follow-up period . Mean systolic blood pressure dropped by 16.1 mm Hg to 127.4 mm Hg in the intensive target arm and by 12.8 mm Hg to 129.4 mm Hg in the standard arm  mm Hg; P=0.03).Conclusions Aiming for target below 130 mm Hg rather than 140 mm Hg for systolic blood pressure in people with cerebrovascular disease in primary care led to a small additional reduction in blood pressure. Active management of systolic blood pressure in this population using a <140 mm Hg target led to a clinically important reduction in blood pressure.Trial registration Current Controlled Trials ISRCTN29062286. Stroke accounts for about 10% of deaths internationally and for more than 4% of direct healthcare costs in developed countries.4The PROGRESS trial showed that treatment to lower blood pressure in people who have had a stroke or TIA reduces the risk of further stroke.13In view of these controversies, the Prevention After Stroke—Blood Pressure (PAST-BP) study compared two different targets for blood pressure lowering after stroke or TIA in people recruited from a prevalent primary care population.The methods used in PAST-BP have been reported in detail elsewhere.The central study team at the University of Birmingham randomised patients, with minimisation based on age, sex, diabetes mellitus, atrial fibrillation, baseline systolic blood pressure, and general practice. The research nurse ascertained treatment allocation either by telephone or online.Neither participants nor clinicians were blinded to treatment allocation. A research nurse who was not otherwise involved in the patient’s care obtained the primary outcome measure (blood pressure) by using an automated sphygmomanometer.Patients randomised to the intensive arm were given a target systolic blood pressure of below 130 mm Hg or a target reduction of 10 mm Hg if their baseline blood pressure was between 125 and 140 mm Hg. The target in the standard arm was less than 140 mm Hg, irrespective of baseline blood pressure. Apart from the different blood pressure targets, the management of blood pressure was the same in both groups and was carried out by a practice nurse (to monitor blood pressure) and a general practitioner (responsible for modifying blood pressure treatment). Patients whose systolic blood pressure at baseline was above target (everyone in the intensive arm and those patients in the standard arm whose blood pressure was ≥140 mm Hg) had their antihypertensive treatment reviewed by their general practitioner. A practice nurse would see all patients at three month intervals (if their blood pressure was below target when previously measured) or after one month (if previous blood pressure was above target) and refer to the general practitioner if the blood pressure was above target. The protocol required no formal down-titration of treatment if blood pressure was below target, but general practitioners had discretion to change or reduce treatment in the light of symptoms attributable to blood pressure drugs. We provided general practitioners with treatment protocols that reflected the national guidelines for blood pressure lowering in operation at the time of the trial.The primary outcome was change in systolic blood pressure between baseline and one year. Participants had blood pressure measured by a research nurse (separate from the practice nurse’s measurements described above) at baseline and at six and 12 months. Blood pressure was measured using a British Hypertension Society validated automated electronic monitor supplied and validated for the study.Secondary measures of blood pressure included diastolic blood pressure at six and 12 months, systolic blood pressure at six months, and proportion achieving target blood pressures at 12 months. For the systolic blood pressure, we also calculated the means of readings 2-6 and 5-6 to look for any differential effects with regard to habituation to blood pressure measurement.We identified clinical events through review of the general practice record at 12 months. These comprised major cardiovascular events , emergency hospital admissions, and deaths. Participants were flagged for mortality at the NHS Central Register. Side effects were assessed through the use of standard questionnaires.14We estimated that a sample size of 305 patients in each group would detect a 5 mm Hg difference in systolic blood pressure between groups with 90% power at a significance level of 5% assuming a standard deviation of 17.5 mm Hg, 10% loss to follow-up, 5% mortality, and 10% major vascular events.The study was discussed by a stroke survivor group who agreed that it was an important research question and that blood pressure was an important outcome for them. Patients were involved in developing plans for recruitment and design of the study through representation on the Trial Steering Committee. No patients were asked to advise on interpretation or writing up of the results. We plan to disseminate the results of the research to the relevant patient community through local and nationally organised stroke groups..Table 1Figure 1v 1; P<0.001) and practice nurse  than the standard target arm. This higher consultation rate led to more intensifications of blood pressure treatment  and more changes due to side effects . However, patients were also less likely to have their blood pressure treatment increased after review by the general practitioner when the blood pressure was above target in the intensive arm  ; P=0.59), as were those achieving a systolic blood pressure below 130 mm Hg (103/182 (57%) v 107/197 (54%); P=0.36). We found no evidence of a significant difference in effectiveness of using an intensive blood pressure target in any subgroup of patients (fig 2Treatment to a more intensive target was associated with a significantly greater reduction in systolic blood pressure at 12 months (primary outcome)  and five in the standard care arm  . Two deaths occurred in the intensive target arm and one in the standard target arm. The risk of emergency admission was 12.8% per year in the intensive target arm and 7.8% per year in the standard target arm . Two admissions in each arm were related to falls. Apart from TIA (responsible for five admissions in the standard target arm and three admissions in the intensive target arm) and stroke, no single diagnosis accounted for more than two admissions. Table 4We found that aiming for a target systolic blood pressure of below 130 mm Hg or a 10 mm Hg reduction from baseline if this was below 140 mm Hg in a primary care population with prevalent cerebrovascular disease led to a lower systolic blood pressure than if a target of below 140 mm Hg target was aimed for. However, the difference was small (about 3 mm Hg) and was associated with increased workload . The intensive target arm was not associated with more side effects as measured at follow-up, but more changes to treatment occurred because of side effects during the trial. More people from the intensive target arm withdrew consent for the trial, and this might have reflected unwillingness to persevere with the increased treatment regimen. Perhaps the most important finding was the greater than 10 mm Hg reductions in mean systolic blood pressure in both arms of the study, so that more than 80% of participants in each arm had achieved a blood pressure of below 140 mm Hg by the end of the trial, compared with less than 50% at baseline.Blood pressure at 12 months was not available for 28% of patients randomised. This reflected a high number of withdrawals from the study, with some differential loss to follow-up in the intensive target arm. However, when we imputed missing values by using multiple imputation (the most robust method), the difference in achieved blood pressure between arms at one year was very similar to that observed. Although we did not achieve our sample size, in the event our trial was adequately powered, as the observed standard deviation in blood pressure was less than we had anticipated in our sample size calculation. This is reflected in the statistical significance of the small difference in observed blood pressure between arms. Nevertheless, the upper limit of the confidence interval around the difference between arms at one year was 5.68 mm Hg, which would be regarded as a clinically important effect. Only 4% of patients on general practice stroke/TIA registers participated in the trial. Participants had a low prevalence of disability for a prevalent cerebrovascular disease population, were younger than typical patients in primary care with a history of cerebrovascular disease, and over-represented people with a history of TIA only.The standard target arm in PAST-BP was actively managed, with the support of a computer based algorithm that suggested drug changes, rather than simply receiving “usual care.” If we had used a more passive management strategy in the comparison group, we may have achieved a greater separation in systolic blood pressure between arms. In another blood pressure lowering study of patients with increased cardiovascular risk carried out by our group in the same timeframe, the standard care control arm dropped by 6 mm Hg from a similar baseline compared with 13 mm Hg in the study reported here.The change in mean blood pressure that we observed in the intensive target arm was very similar to that observed in the below 130 mm Hg target arm of the SPS3 trial, with both PAST-BP and SPS3 achieving a mean systolic blood pressure in the intensive arm of 127 mm Hg after one year.Most of the observed reduction in blood pressure is likely to have been mediated by increased use of antihypertensive drugs, which on average went up from one to two drugs per person over the year of the study in both arms of the trial. Alternative explanations are that habituation to blood pressure measurement occurred, leading to reduced white coat effect, or that there was regression dilution bias. However, in a blood pressure monitoring trial in a similar post-stroke population with similar mean baseline systolic blood pressure, no fall in blood pressure was observed in the control group over a 12 month period,Only 51% of patients in the intensive target arm of PAST-BP achieved their target blood pressure. Both patients’ wishes and general practitioners’ decision making led to treatment not being intensified when blood pressure was above target  in the context of the reduction in blood pressure observed in both arms (13 mm Hg and 16 mm Hg)Active management of blood pressure after stroke/transient ischaemic attack is more important than the target that is set