Xinli Li

Blood Pressure and Renal Sodium Handling in Relation to Genetic Variation in the DRD1 Promoter and GRK4

Activation of type-1 dopamine receptors (DRD1) reduces renal sodium reabsorption. In a family-based random sample of 611 untreated whites (women, 45.0%; mean age, 38.6 years), we measured blood pressure (BP). We used the endogenous lithium clearance to assess fractional sodium excretion (FENa) and proximal (RNaprox) and distal (RNadist) tubular sodium reabsorption. We investigated multivariate-adjusted associations with the DRD1 promoter (A−48G, G−94A, and C−800T) and GRK4 (Ala142Val). The frequent DRD1 haplotypes were AGC (48.2%), GGT (34.4%), and AAC (14.3%). While standardizing to mean sodium excretion (8.7 mmol/h) and adjusting for covariates and relatedness, RNadist was lower in DRD1 −94GG homozygotes than −94A allele carriers (effect size, −0.94%; P=0.005) with opposite findings for FENa (+0.084%; P=0.014). AGC carriers (−0.88%; P=0.012) and AAC carriers (+1.00%; P=0.004) had different RNadist compared to corresponding noncarriers. Furthermore, FENa was lower in AAC carriers than in noncarriers (−0.082%; P=0.019). The family-based analyses identified a significant between-family component in the variance of the renal phenotypes associated with the DRD1 polymorphisms. Transmission of the DRD1 AGC haplotype was also associated with lower systolic (−3.54 mm Hg; P=0.016) and diastolic (−2.80 mm Hg; P=0.0064) BPs without significant between-family variance component. Plasma renin activity and urinary aldosterone excretion were not associated with DRD1 variation. The GRK4 Ala142Val polymorphism did not contribute to the phenotypes under study. In conclusion, renal sodium handling and BP were associated with genetic variation in the DRD1 promoter. The between-family variance component excluded population stratification for BP, but not for the renal phenotypes.

Progression to hypertension in the non-hypertensive participants in the Flemish Study on Environment, Genes and Health Outcomes.

Objective To evaluate the consistency between a randomly recruited Western European population and the participants of the Framingham Heart Study, with respect to the rates and determinants of progression to hypertension. Methods Among the non-hypertensive individuals enrolled in the Flemish Study on Environment, Genes and Health Outcomes, we assessed progression from optimal (< 120/80 mmHg), normal (120–129/80–84 mmHg) and high-normal (130–139/85–89 mmHg) blood pressure to hypertension (≥ 140/90 mmHg). Our analysis included 781 women and 675 men (age range 10–77 years) who were followed up for a median of 4.6 years (interquartile range 2.4–8.1 years). Our statistical methods included Kaplan–Meier survival function estimates, the log-rank test and multiple Cox regression. Results In individuals younger than 50 years, 4-year progression rates associated with optimal, normal and high-normal blood pressure were 7.4% [95% confidence interval (CI) 5.5–9.3], 17.9% (95% CI 14.3–21.6) and 24.5% (95% CI 18.7–30.2), respectively. Corresponding 4-year rates of progression for individuals aged 50 years or older were 16.4% (95% CI 11.2–22.5), 26.3% (95% CI 19.8–32.9) and 54.0% (95% CI 45.7–62.3), respectively. In multivariate Cox regression, blood pressure category and body mass index at baseline were strong predictors of hypertension. Before the age of 50 years, male sex and a fast heart rate were also forerunners of hypertension. Conclusions The stepwise increase in incidence of hypertension across the three non-hypertensive blood pressure categories in our cohort was similar to that observed in the Framingham Heart Study. The Framingham findings, which have informed several guidelines, can be extrapolated to a Western European population.

Cardiovascular and metabolic phenotypes in relation to the ADRA2B insertion/deletion polymorphism in a Chinese population.

Objective The functional ADRA2B I/D polymorphism is associated with various cardiovascular and metabolic phenotypes in Caucasians. The purpose of our study was to investigate whether the ADRA2B I/D polymorphism is associated with such phenotypes in a Chinese population. Methods We enrolled 247 women and 234 men in a family-based Chinese study. Our statistical methods included generalized estimating equations and quantitative transmission disequilibrium test. Results The I allele (62.3 versus 50.8%, P = 0.015) and the II genotype (40.9 versus 23.4%, P = 0.017) were more prevalent among hypertensive than normotensive men. While adjusting for covariates and family clusters, male II homozygotes compared with D-allele carriers had higher systolic pressure (130.0 versus 125.0 mmHg, P = 0.016) and a 2.61 times greater (P = 0.008) risk of hypertension. On the other hand, II homozygous men had lower body weight (65.4 versus 69.6 kg, P = 0.008), body mass index (23.4 versus 24.5 kg/m2, P = 0.037), waist-to-hip ratio (0.838 versus 0.857, P = 0.024), serum insulin concentration (9.5 versus 13.2 mU/l, P = 0.026) and insulin resistance (homeostasis model assessment index 2.4 versus 3.2, P = 0.051). None of these associations reached statistical significance in women. In 65 informative male offspring, transmission of the I allele was associated with higher systolic pressure (+ 6.0 mmHg, P = 0.10), diastolic pressure (+ 5.5 mmHg, P = 0.021), and faster pulse rate (+ 5.8 beats/min, P = 0.019). Conclusion In Chinese men, the I allele of the ADRA2B gene is associated with higher blood pressure, but also with a more favourable metabolic phenotype.

Relationship between brachial-ankle pulse wave velocity and metabolic syndrome components in a Chinese population.

Abstract The purpose of this study was to assess the relationship between arterial stiffness, as measured by brachial-ankle pulse wave velocity (baPWV), and the presence of the metabolic syndrome (MS) in a Chinese population. A total of 4,445 subjects were enrolled. The prevalence of MS in our study population was 21.7%, 17.2% and 25.6% for the general population, males and females, respectively. With adjustments for age, gender, cigarette smoking, heart rate, total cholesterol, low-density lipoprotein (LDL) cholesterol, and the use of anti-hypertensive drug, the stepwise regression analysis showed that baPWV had a significant relationship with components of MS, including systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.001), glucose (P < 0.001), high-density lipoprotein (HDL) cholesterol (P u200a=u200a 0.04), and triglycerides (P < 0.001), but no relationship with waist circumference (P u200a=u200a 0.25). With an increase in the number of the MS components, baPWV increased significantly both in women and men. This study indicated that the MS is indeed a risk factor for arterial stiffness. Monitoring of baPWV in patients with MS may help in identifying persons at high risk for cardiovascular disease.

Physical activity modifies the association between CYBA gene polymorphisms and small artery elasticity in a Chinese population

Emerging evidence suggests that increased superoxide production is responsible for a significant proportion of endothelial dysfunction. The relationship between variants of the CYBA gene and cardiovascular diseases is currently debated. In the present study, we investigated the influence of CYBA polymorphisms (rs1049255 and rs7195830) on arterial elasticity in a Chinese population. In the 2178 participants enrolled in the GaoYou study, we measured large artery elasticity (C1) and small artery elasticity (C2) non-invasively, genotyped the CYBA polymorphisms and calculated energy expenditure. The AA genotype of the rs1049255 polymorphism was associated with a lower C2 than were the GG/AG genotypes (5.31±0.11 vs. 5.52±0.06u2009mlu2009mmu2009Hg−1 × 100; P=0.01). Further analyses revealed an interaction between CYBA polymorphisms and physical activity with respect to C2 (P=0.007 for rs1049255 and P=0.038 for rs7195830). In less physically active participants, the AA genotype of the rs1049255 polymorphism was associated with a significantly lower C2 than the GG/AG genotypes (4.69±0.16 vs. 5.26±0.19u2009mlu2009mmu2009Hg−1 × 100; P=0.008). In physically active participants, the GG/AG genotypes of rs7195830 polymorphism were correlated with higher C2 values than the AA genotype (5.84±0.08 vs. 5.08±0.32u2009mlu2009mmu2009Hg−1 × 100; P=0.049). Haplotype analyses revealed higher C2 values in rs1049255G–rs7195830G carriers (P=0.0015). In conclusion, the rs1049255 and rs7195830 polymorphisms of the CYBA gene were associated with C2 in a Chinese population; physical activity could modify this genetic effect.

Predictors of Long-Term Mortality in Patients With Acute Heart Failure

To investigate parameters which were related with long-term mortality in patients hospitalized for acute heart failure (AHF).A total of 287 patients with AHF presenting to the First Affiliated Hospital of Nanjing Medical University were enrolled into the registry from April 2012 to January 2015. The primary endpoint was all-cause mortality within 1 year; the association between variables and prognosis was assessed after 1 year.Among the 287 patients, 17 did not continue follow-up and 47 (17.4%) passed away. Baseline NT-proBNP and sST2 concentrations were higher amongst deceased than among survivors (P < 0.001). Serum sodium concentrations of patients who died were lower (P < 0.001). In receiver operator characteristics (ROC) analyses, the area under the curve (AUC) values for NT-proBNP, sST2, and serum sodium to predict 1-year mortality were 0.699 (95%CI 0.639-0.755), 0.692, (95%CI 0.634-0.747), and 0.694 (95%CI 0.634-0.750), respectively. The optimal cut-off points for NT-proBNP, sST2, and serum sodium were 2137.0 ng/L, 35.711 ng/mL, and 136.6 mmol/L, respectively. In Cox regression analysis, ln-transformed NT-proBNP (HR 1.546, P = 0.039), ln-transformed sST2 (HR1.542, P = 0.049), and serum sodium (HR 0.880, P = 0.000) values reliably predicted long-term mortality after multivariable adjustment.In patients with acute heart failure, NT-proBNP, sST2 and serum sodium are potential predictors of 1-year mortality.

Quality control of the blood pressure phenotype in the Gaoyou population study.

Abstract The Korotkoff approach is the only blood pressure (BP) measurement technique that allows contemporary data to be compared with decades of research. We randomly recruited 4483 people (53.3% women; mean age 52.1 years) from Gaoyou County, Jiangsu Province, China. Nine observers recorded the participants™ BP three times consecutively following Chinese Society of Hypertension guidelines. We assessed the BP phenotype based on five criteria: completeness of readings, percentage of identical BP readings, odd BP readings, end-digit preference and trends in BP from the first to the third reading. The proportion of participants with identical readings were 2.0% and 3.1% for systolic (SBP) and diastolic blood pressure (DBP), respectively. Among 26,898 BP values, 0.3% ended in an odd number. Among observers, the prevalence of identical readings varied from 0% to 5.3% for SBP and from 0% to 6.8% for DBP. Compared with the expected frequency of 20%, those ending in 0 had a lower frequency (17.2%; pu2009<u20090.001), whereas those ending in 8 had a higher frequency (22.4%; pu2009<u20090.001). From the first to the third measurement, SBP and DBP decreased (pu2009<u20090.001) by 0.87 and 0.55 mmHg, respectively. In conclusion, the procedures set up in the Gaoyou study produced a high-quality BP phenotype.

Hypertension related knowledge and behaviour associated with awareness, treatment and control of hypertension in a rural hypertensive population: a community based, cross-sectional survey

Abstract Background and objective: Hypertension-related knowledge and behaviour have been identified as influential factors associated with awareness, treatment and control of hypertension in urban regions. However, there were few studies on rural areas. This study aims to investigate whether hypertension related knowledge and behaviour were associated with hypertension awareness, treatment and control in Gaoyou, a rural area of Jiangsu province, China. Methods: A cross-sectional, population-based survey was conducted among hypertensive individuals in rural areas of Gaoyou, the south-eastern of China in 2010. We identified 1943 subjects with hypertension among 4536 subjects participated in this study and collected information about medical history, use of medication, hypertension related knowledge and behaviour by a standardized questionnaire. Results: This study showed that 41.07% of subjects were aware of their disease, 30.01% of subjects were taking antihypertensive medication and 5.04% of subjects controlled their blood pressure. Multivariate logistic regression analysis showed that subjects who knew the threshold, the lifelong treatment of hypertension and measured blood pressure at least once a year had better detection, treatment or control of hypertension. Conclusion: Hypertension related knowledge and behaviour were associated with awareness, treatment and control rate of hypertension in the rural areas of south-eastern China.

Do genotype-based changes in serum uric acid really affect blood pressure?

To the Editor: Parsa et al.1 used Mendelian randomization to test the causal association between serum uric acid (SUA) and blood pressure. They found that decreases in SUA concentration due to a missense single-nucleotide polymorphism in the GLUT9 gene are directly associated with a lower level of blood pressure and concluded that SUA is causally associated with blood pressure. However, in the association analysis of SUA and blood pressure, only age and gender were adjusted. We are wondering whether the association between SUA and blood pressure remains significant upon further adjustment for other important covariates. Actually, a previous study has shown that the relationship between SUA and blood pressure was attenuated by up to 50% upon further adjustment for body mass index, waist–hip ratio, or body fat percent.2 A recent meta-analysis has found a modest but significantly increased relative risk for incident hypertension in subjects with hyperuricemia, independent of traditional risk factors for hypertension.3 However, adjusting for measures of insulin resistance could bias the effect estimates toward the null.3 In our cross-sectional study including 4387 subjects randomly selected from a general population, SUA was significantly associated with systolic and diastolic blood pressures adjusting for gender and age, but the association was no longer significant after the further adjustment of body mass index and waist–hip ratio (Table 1). If the association between SUA and blood pressure is no longer significant after complete adjustment, then the causal association might not be proved even with the use of Mendelian randomization.