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Background: Premature death from suicide is a leading cause of death worldwide. However, the pattern and risk factors for suicide and other external cause injuries are not well understood. This study investigates mortality from suicide and other injuries and associated risk factors in China. Methods: A prospective cohort study of 169,871 Chinese adults aged 40 years and older was conducted. Mortality due to suicide or other external cause injuries was recorded. Results: Mortality from all external causes was 58.7/100,000 (72.3 in men and 44.4 in women): 14.1/100,000 (14.2 in men and 14.2 in women) for suicide and 44.6/100,000 (58.1 in men and 30.2 in women) for other external cause injuries. Transport accidents (17.2/100,000 overall, 23.4 in men and 10.8 in women), accidental poisoning (7.5/ 100,000 overall, 10.2 in men and 4.8 in women), and accidental falls (5.7/100,000 overall, 6.5 in men and 5.0 in women) were the three leading causes of death from other external cause injuries in China. In the multivariable analysis, male sex (relative risk [RR] 1.56, 95% confidence interval [CI] 1.03-2.38), age 70 years and older (2.27, 1.29- 3.98), living in north China (1.68, 1.20-2.36) and rural residence (2.82, 1.76-4.51) were associated with increased mortality from suicide. Male sex (RR 2.50, 95% CI 1.95-3.20), age 60-69 years (1.93, 1.45-2.58) and 70 years and older (3.58, 2.58-4.97), rural residence (2.29, 1.77-2.96), and having no education (1.56, 1.00-2.43) were associated with increased mortality from other external cause injuries, while overweight (0.60, 0.43-0.83) was associated with decreased risk of mortality from other external cause injuries. Conclusions: External cause mortality has become a major public health problem in China. Developing an integrated national program for the prevention of mortality due to external cause injuries in China is warranted. [ABSTRACT FROM AUTHOR]

A large proportion of the phenotypic variation in blood pressure (BP) appears to be inherited as a polygenic trait. This study examined the association between 12 single nucleotide polymorphisms (SNPs) in the guanine nucleotide binding protein beta polypeptide 3 ( GNB3) and adducin 1 alpha ( ADD1) genes and systolic (SBP), diastolic (DBP), and mean arterial (MAP) BP. A total of 3,142 individuals from 636 families were recruited from rural north China, and 2,746 met the eligibility criteria for analysis. BP measurements were obtained using a random-zero sphygmomanometer. Genetic variants were determined using SNPlex assays on an automated DNA Sequencer. A mixed linear model was used to estimate the association between each SNP and BP level. After Bonferroni correction, marker rs4963516 of the GNB3 gene remained significantly associated with DBP (corrected P values = 0.006, 0.007 and 0.002 for co-dominant, additive, and recessive models, respectively) and MAP (corrected P values = 0.02, 0.049, and 0.005, respectively). Compared to carriers of the major A allele, CC homozygotes had higher mean DBP (75.81 ± 0.62 vs. 73.46 ± 0.25 mmHg, P = 0.0002) and MAP (91.87 ± 0.68 vs. 89.42 ± 0.28 mmHg, P = 0.0004) after adjusting for covariates of age, gender, BMI, study site, and room temperature during BP measurement. In summary, these data support a role for the GNB3 gene in BP regulation in the Chinese population. Future studies aimed at replicating these novel findings are warranted. [ABSTRACT FROM AUTHOR]

BackgroundGenetic determinants of blood pressure (BP) responses to the cold pressor test (CPT), a phenotype associated with risk of hypertension and cardiovascular disease has not been well studied.MethodsWe examined the heritability of BP response to CPT in 1,994 subjects from 627 families in rural north China. BP was measured before and at 0, 1, 2, and 4 min after the participants immersed their hand in ice water for 1 min. Heritabilities of baseline BP and responses at 0 min, maximum response, and area-under-the-curve (AUC) during CPT were computed using a variance components method. Additionally, bivariate heritabilities were calculated to test the existence of shared genetic determinants between baseline BP and responses to CPT.ResultsHeritabilities of baseline BP and responses to CPT were estimated from 14 to 35%, which all significantly differed from 0 (P ≤ 0.002). Genetic correlations (s.e.) due to the same genes between baseline BP and responses to CPT ranged from −0.07 (0.14) to 0.21 (0.15), which were not significantly different from 0. Genetic correlations between reactivity and recovery were 0.67 (0.10) and 0.59 (0.10) for systolic (SBP) and diastolic BP (DBP), respectively, which were significantly different from 0.ConclusionsWe concluded that (i) baseline BP and BP responses to CPT had strong genetic determinants; (ii) baseline BP and BP response to CPT did not share the same genetic components; and (iii) BP reactivity and recovery shared the same genetic components. These findings may lead to a better understanding of the genetic mechanism of BP responses to CPT.American Journal of Hypertension 2009; doi:10.1038/ajh.2009.139 [ABSTRACT FROM AUTHOR]

Background: Smoking is a risk factor for many diseases and has been increasingly prevalent in economically developing regions of the world. We aimed to estimate the number of deaths attributable to smoking in China. Methods: We conducted a large, prospective cohort study in a nationally representative sample of 169,871 Chinese adults who were 40 years of age or older. Investigators for the China National Hypertension Survey collected data on smoking and other risk factors at a baseline examination in 1991 using a standard protocol. Follow-up evaluation was conducted in 1999 and 2000, with a response rate of 93.4%. We used multivariable-adjusted relative risk, prevalence of smoking, mortality, and population size in each age group, stratified according to sex, to calculate the number of deaths attributable to smoking in 2005. Results: There was a significant, dose–response association between pack-years smoked and death from any cause in both men and women after adjustment for multiple risk factors (P<0.001 for trend). We estimated that in 2005, a total of 673,000 deaths (95% confidence interval [CI], 564,700 to 781,400) were attributable to smoking in China: 538,200 (95% CI, 455,800 to 620,600) among men and 134,800 (95% CI, 108,900 to 160,800) among women. The leading causes of smoking-related deaths were as follows: cancer, 268,200 (95% CI, 214,500 to 321,900); cardiovascular disease, 146,200 (95% CI, 79,200 to 213,100); and respiratory disease, 66,800 (95% CI, 20,300 to 113,300). Conclusions: Our study documents that smoking is a major risk factor for mortality in China. Continued strengthening of national programs and initiatives for smoking prevention and cessation is needed to reduce smoking-related deaths in China. N Engl J Med 2009;360:150-9. [ABSTRACT FROM AUTHOR]

BACKGROUND We examined the relationship between systolic and diastolic blood pressure (BP) and the incidence of cardiovascular disease (CVD) in a nationally representative cohort of 169,871 men and women ≥40 years of age in China. METHODS Data on BP and other variables were obtained at a baseline examination in 1991 using standard protocols. Follow-up evaluation was conducted in 1999-2000, with a response rate of 93.4%. RESULTS After adjustment for age, sex, cigarette smoking, alcohol consumption, physical activity, body mass index, education, geographic region, urbanization, and time-dependent history of diabetes, a strong and linear association between both systolic and diastolic BP and incidence of CVD, coronary heart disease and stroke were observed (all P < 0.0001). For example, the relative risks (95% confidence interval (CI)) of CVD incidence were 1.09 (1.00-1.18), 1.25 (1.16-1.35), 1.49 (1.38-1.62), 2.15 (1.99-2.31), 3.01 (2.78-3.27), and 4.16 (3.84-4.51) for those with systolic/diastolic BP of 110-119/75-79, 120-129/80-84, 130-139/85-89, 140-159/90-99, 160-179/100-109, and ≥180/110 mm Hg compared to those with BP <110/75 mm Hg. Increases in systolic BP were associated with a greater risk of CVD compared to corresponding increases in diastolic BP. The linear trend for increased CVD risk being related to higher BP levels was observed in all subgroups of gender, age, body weight, and cigarette smoking. CONCLUSIONS Our results indicate that there is a strong, linear, and independent relationship between BP levels and the risk of CVD in Chinese adults. Systolic BP is a stronger predictor of CVD risk compared to diastolic BP. [ABSTRACT FROM AUTHOR]

The relation between parental history of hypertension and blood pressure response to potassium intake is unknown. A 7-day high-sodium followed by a 7-day high-sodium plus potassium dietary-feeding study was conducted from 2003 to 2005 among 1,871 Chinese participants. Those with a maternal history of hypertension had larger systolic blood pressure responses to potassium compared with those without: −4.31 (95% confidence interval (CI): −4.99, −3.62) mm Hg versus −3.35 (95% CI: −4.00, −2.70) mm Hg, respectively (Pdifference = 0.002). A consistent trend was observed for diastolic blood pressure responses: −1.80 (95% CI: −2.41, −1.20) mm Hg versus −1.35 (95% CI: −1.95, −0.74) mm Hg, respectively (P = 0.07). Stronger associations between early onset maternal hypertension and blood pressure responses were noted, with systolic blood pressure decreases of −4.80 (95% CI: −5.65, −3.95) mm Hg versus −3.55 (95% CI: −4.17, −2.93) mm Hg and diastolic blood pressure decreases of −2.25 (95% CI: −3.01, −1.50) mm Hg versus −1.42 (95% CI: −1.99, −0.85) mm Hg among those with early onset maternal hypertension versus those without, respectively (P = 0.001 and 0.009, respectively). Odds ratios for high potassium sensitivity were 1.36 (95% CI: 0.96, 1.92) and 1.60 (95% CI: 1.08, 2.36) for those with maternal hypertension and early onset maternal hypertension, respectively (P = 0.08 and 0.02, respectively). Potassium supplementation could help to reduce blood pressure among those with a maternal history of hypertension. [ABSTRACT FROM PUBLISHER]

The current study comprehensively examined the association between common genetic variants of the kallikrein-kinin system (KKS) and blood pressure salt sensitivity. A 7-day low-sodium followed by a 7-day high-sodium dietary intervention was conducted among 1,906 Han Chinese participants recruited from 2003 to 2005. Blood pressure was measured by using a random-zero sphygmomanometer through the study. A total of 205 single nucleotide polymorphisms (SNPs) covering 11 genes of the KKS were selected for the analyses. Genetic variants of the bradykinin receptor B2 gene (BDKRB2) and the endothelin converting enzyme 1 gene (ECE1) showed significant associations with the salt-sensitivity phenotypes even after adjustment for multiple testing. Compared with the major G allele, the BDKRB2 rs11847625 minor C allele was significantly associated with increased systolic blood pressure responses to low-sodium intervention (P = 0.0001). Furthermore, a haplotype containing allele C was associated with an increased systolic blood pressure response to high-sodium intervention (P = 0.0009). Seven highly correlated ECE1 SNPs were shown to increase the diastolic blood pressure response to low-sodium intervention (P values ranged from 0.0003 to 0.002), with 2 haplotypes containing these 7 SNPs also associated with this same phenotype (P values ranged from 0.0004 to 0.002). In summary, genetic variants of the genes involved in the regulation of KKS may contribute to the salt sensitivity of blood pressure. [ABSTRACT FROM PUBLISHER]

An elevated blood pressure (BP) response to the cold pressor test (CPT) is associated with increased risk of hypertension and cardiovascular disease. However, it is still unclear whether BP response to the CPT is a stable and reproducible trait over time. Using the same study protocol, the authors repeated the CPT 4.5 years after initial administration among 568 Han Chinese in rural northern China (2003–2005 and 2008–2009). BP was measured using a standard mercury sphygmomanometer prior to and 0, 1, 2, and 4 minutes after the participants immersed their hand in ice water (3°C–5°C) for 1 minute. Absolute BP levels and BP responses during the CPT in the initial and repeated administrations were highly correlated. For example, the correlation coefficients were 0.67, 0.73, 0.71, and 0.72 for absolute systolic BP levels at 0, 1, 2, and 4 minutes after ice-water immersion (all P 's < 0.0001). The correlation coefficients for systolic BP response were 0.41 at 0 minutes, 0.37 at 1 minute, 0.42 for maximum response, and 0.39 for the area under the curve during CPT (all P 's < 0.0001). These data indicate that BP response to the CPT is a long-term reproducible and stable characteristic in the general population. [ABSTRACT FROM PUBLISHER]

The authors conducted a genome-wide linkage scan and positional association analysis to identify the genetic determinants of salt sensitivity of blood pressure (BP) in a large family-based, dietary-feeding study. The dietary intervention was conducted among 1,906 participants in rural China (2003–2005). A 7-day low-sodium intervention was followed by a 7-day high-sodium intervention. Salt sensitivity was defined as BP responses to low- and high-sodium interventions. Signals of the logarithm of the odds to the base 10 (LOD ≥ 3) were detected at 33–42 centimorgans of chromosome 2 (2p24.3-2p24.1), with a maximum LOD score of 3.33 for diastolic blood pressure responses to high-sodium intervention. LOD scores were 2.35–2.91 for mean arterial pressure (MAP) and 0.80–1.49 for systolic blood pressure responses in this region, respectively. Correcting for multiple tests, single nucleotide polymorphism (SNP) rs11674786 (2.7 kilobases upstream of the family with sequence similarity 84, member A, gene (FAM84A)) in the linkage region was significantly associated with diastolic blood pressure (P = 0.0007) and MAP responses (P = 0.0007), and SNP rs16983422 (2.8 kilobases upstream of the visinin-like 1 gene (VSNL1)) was marginally associated with diastolic blood pressure (P = 0.005) and MAP responses (P = 0.005). An additive interaction between SNPs rs11674786 and rs16983422 was observed, with P = 7.00 × 10−5 and P = 7.23 × 10−5 for diastolic blood pressure and MAP responses, respectively. The authors concluded that genetic region 2p24.3-2p24.1 might harbor functional variants for the salt sensitivity of BP. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Recent studies suggest that central obesity is an important predictor of cardiovascular disease (CVD) in addition to overall obesity. Both inflammation and endothelial dysfunction are associated with increased risk of CVD. We examined the association between body mass index (BMI) and waist circumference (WC) with plasma concentrations of biomarkers of inflammation and endothelial dysfunction. Methods: We conducted a cross-sectional study of 2589 lean, moderately active participants aged 20years and older in Inner Mongolia, China. Overnight fasting blood samples were obtained to measure the biomarkers including C-reactive protein (CRP), soluble inter-cellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), and angiotensin II. Height, body weight, and WC were measured by trained staff and BMI was calculated (kg/m2). Results: In univariate analysis, CRP, sICAM-1, and sE-selectin were all significantly higher among individuals with a higher BMI and WC. In multivariate analysis, each standard deviation (SD) increase in WC (9.6cm) was associated with about 46% higher risk (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.21–1.76) of elevated CRP but a 1 SD increase in BMI (3.5kg/m2) was not associated with the risk of elevated CRP (OR 0.96, 95% CI 0.80–1.16). However, each SD increase in BMI was associated with about 30% higher risk of having elevated E-selectin (OR 1.30, 95% CI 1.08–1.55). Conclusions: WC is a stronger predictor of inflammation while BMI is a stronger predictor for endothelial dysfunction. These results suggest measuring both BMI and WC will help to assess the risk of CVD in the Chinese population. [Copyright &y& Elsevier]

The article focuses on a study which explored the prevalence of premature deaths that are related to increased blood pressure in China. The study included 169,871 Chinese adult who are 40 years and above. It defined premature death as the mortality that occurred before the age of 72 in men and 75 in women. Population-related risk, mortality and population size in China in 2005 were considered in computing the rate of total and premature deaths in the country. The study found that hypertension and prehypertension were linked with increased all-cause and cardiovascular mortality. Study authors concluded that since hypertension is preventable, it should be given priority in the country.

Background Ischemic stroke is likely caused by interactions of multiple genes and environmental determinants. However, large-scale sequencing studies to discern functional genetic variants and their interactions with clinical and lifestyle risk factors on ischemic stroke are limited. Methods and Results We sequenced functional regions of 740 previously identified genes associated with atherosclerotic disease among 999 ischemic stroke cases and 1001 controls of Chinese ancestry. Multiple logistic regression models were used to examine the associations between variants and ischemic stroke and test interactions between variants and clinical and lifestyle risk factors. Functional variants achieving suggestive significance were replicated in an independent sample of 4724 ischemic stroke cases and 5029 controls. Driven by variant main effects, each minor allele of the correlated rs174535, rs174545, and rs3834458 variants at MYRF-FADS1-FADS2 conferred an average 0.83-fold (95% CI, 0.78-0.88) decreased odds of stroke. Significant main effects of MTHFR rs1801133 missense variant were also observed, with each copy of the A allele associated with a 1.20-fold (95% CI, 1.13-1.27) higher odds of ischemic stroke. The functional ALDH2 rs671 variant was identified in interaction analyses with alcohol drinking ( Meta-P =3.39×10 -17 ). Each minor allele conferred a 0.54-fold (95% CI, 0.45-0.64) decreased odds of stroke among drinkers and a 0.89-fold (95% CI, 0.83-0.97) decreased odds among nondrinkers. Conclusions Significant associations at MYRF-FADS1-FADS2 indicate that genetically elevated polyunsaturated fatty acids may decrease ischemic stroke risk in East Asians. Significant associations at MTHFR and ALDH2 robustly confirm deleterious effects of genetically elevated homocysteine and alcohol intake, respectively, on ischemic stroke.

Genetic mechanisms involved in the susceptibility to salt sensitivity have not been completely clarified. This study aimed to comprehensively examine the association between genetic variants in the cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG/PRKG) genes and blood pressure (BP) responses to dietary sodium intervention in a Chinese population. A 7-day low-sodium intervention followed by a 7-day high-sodium intervention was conducted among 1906 Han participants from rural areas of northern China. Nine BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive association of 213 tag single-nucleotide polymorphisms (SNPs) in two PRKG genes (PRKG1 and PRKG2) with salt sensitivity phenotypes. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing. Mean systolic BP response to low-sodium intervention significantly decreased with the number of minor T allele of marker rs10997916 in PRKG1 (P = 2.4 × 10 -5 ). Mean systolic BP responses (95% confidence interval) among those with genotypes CC, CT, and TT were -5.6 (-6.0, -5.3), -3.7 (-4.7, -2.8), and -1.3 (-4.6, 2.0) mmHg, respectively, during the low-sodium intervention. Gene-based analyses demonstrated that PRKG1 was significantly associated with systolic BP response to low-sodium intervention (P = 1.2 × 10 -3 ), whereas PRKG2 was nominally significantly associated with diastolic BP responses to high-sodium intervention (P = 2.6 × 10 -2 ). The current study suggested a significant association of genetic variants in the PRKG genes with variation of BP response to dietary sodium intake in Han Chinese population. These novel findings merit further replication in future.

Background: Single-marker and novel gene-based methods were employed to examine the associations of the serum/glucocorticoid regulated kinases (SGK) gene family with longitudinal blood pressure (BP) changes and hypertension incidence in a family-based cohort study., Methods: Totally, 1,768 Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were included in the current analyses. Nine BP measures were obtained at each of 3 visits during the GenSalt follow-up study. Mixed-model and Gene-based analyses were used to examine the associations of the SGK gene family with longitudinal BP phenotypes. Bonferroni correction was applied to account for multiple testing., Results: After an average 7.2-year follow-up, 32.2% (513) of participants free of hypertension at baseline developed hypertension. Four novel SNPs in the SGK1 gene were predictive of the longitudinal BP phenotypes. The major alleles of SGK1 rs1763498 and rs114414980 conferred 2.9- and 2.5-fold increased risks of hypertension development, respectively (P = 1.0×10 -4 and 6.0×10 -4 , respectively). In addition, the major allele of SGK1 rs229133 was significantly associated with 0.4mm Hg larger annual increases in systolic BP (P = 4.2×10 -4 ), while the major allele of rs6924468 was significantly associated with 0.2mm Hg smaller annual increases in diastolic BP (P = 4.2×10 -4 ). Gene-based analyses revealed an association of the SGK1 gene with risk of hypertension development (P = 7.4×10 -3 ). No evidence for the SGK2 and SGK3 genes was found., Conclusions: The findings of the current study suggest that the SGK1 gene may play a role in long-term BP regulation and hypertension incidence., (© American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: We aimed to examine the associations of voltage-dependent calcium-channel genes CACNA1A and CACNA1C with blood pressure (BP) changes and hypertension incidence in a longitudinal family study., Methods: A total of 1,768 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were eligible for the current study. Nine BP measurements were obtained at baseline and each follow-up visit using a random-zero sphygmomanometer. Mixed-effect models were used to assess additive associations of 176 tag single-nucleotide polymorphisms (SNPs) in CACNA1A and CACNA1C with longitudinal BP changes and hypertension incidence. The truncated product method was used for gene-based analysis. The Bonferroni correction was used for adjustment of multiple testing., Results: During an average of 7.2 years of follow-up, 512 (32.1%) participants developed hypertension. CACNA1A SNP rs8182538 was significantly associated with longitudinal diastolic BP (DBP) change after Bonferroni correction ( Pinteraction = 9.90×10 -5 ), with mean DBP increases of 0.85, 1.03, and 1.19mm Hg per year for participants with genotypes C/C , C/T , and T/T , respectively. A similar trend was observed for the association of rs8182538 with systolic BP (SBP) change. In the gene-based analysis, CACNA1A and CACNA1C were significantly associated with DBP change ( P = 2.0×10 -5 ) and SBP change ( P = 1.4×10 -4 ) after Bonferroni correction, respectively. The gene-based associations remained significant after removing rs8182538 within CACNA1A and rs758116 within CACNA1C in sensitivity analysis., Conclusions: Our findings indicated that CACNA1A and CACNA1C might contribute to BP changes over time in Han Chinese population. Further replication of these findings is warranted.

We performed genome-wide analyses to identify genomic loci that interact with sodium to influence blood pressure (BP) using single-marker-based (1 and 2 df joint tests) and gene-based tests among 1876 Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Among GenSalt participants, the average of 3 urine samples was used to estimate sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 2.05 million single-nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00×10(-4)) from GenSalt were evaluated for replication among 775 Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Single-nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for UST rs13211840 on diastolic BP (P=3.13×10(-9)). The 2 df tests additionally identified associations for CLGN rs2567241 (P=3.90×10(-12)) and LOC105369882 rs11104632 (P=4.51×10(-8)) with systolic BP. The CLGN variant rs2567241 was also associated with diastolic BP (P=3.11×10(-22)) and mean arterial pressure (P=2.86×10(-15)). Genome-wide gene-based analysis identified MKNK1 (P=6.70×10(-7)), C2orf80 (P<1.00×10(-12)), EPHA6 (P=2.88×10(-7)), SCOC-AS1 (P=4.35×10(-14)), SCOC (P=6.46×10(-11)), CLGN (P=3.68×10(-13)), MGAT4D (P=4.73×10(-11)), ARHGAP42 (P≤1.00×10(-12)), CASP4 (P=1.31×10(-8)), and LINC01478 (P=6.75×10(-10)) that were associated with at least 1 BP phenotype. In summary, we identified 8 novel and 1 previously reported BP loci through the examination of single-nucleotide polymorphism and gene-based interactions with sodium., (© 2016 American Heart Association, Inc.)

Background: The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure (BP) regulation. The current study uses single-marker and gene-based analyses to examine the association between RAAS genes and longitudinal BP phenotypes in a Han Chinese population., Methods: A total of 1,768 participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were included in the current study. Twenty-seven BP measurements were taken using random-zero sphygmomanometers at baseline and 2 follow-up visits. Mixed-effect models were used to assess the additive associations of 106 single-nucleotide polymorphisms (SNPs) in 10 RAAS genes with longitudinal BP changes and hypertension incidence. Gene-based analyses were conducted using the truncated product method. Attempts were made to replicate significant findings among Asian participants of the Multi-ethnic Study of Atherosclerosis (MESA). False discovery rate procedures were used to adjust for multiple testing., Results: During an average of 7.2 years of follow-up, average systolic and diastolic BP increased, and 32.1% (512) of participants free from hypertension at baseline developed hypertension. NR3C2 SNPs rs7694064 and rs6856803 were significantly associated with longitudinal changes in systolic BP (P interaction = 6.9×10(-5) and 8.2×10(-4), respectively). Through gene-based analysis, NR3C2 was found to be significantly associated with longitudinal systolic BP change (P value of 1.00×10(-7)), even after removal of significant markers rs7694064 and rs6856803 from the analysis. The association between NR3C2 and longitudinal systolic BP change was replicated in Asian MESA participants (P value of 1.00×10(-4))., Conclusions: These findings indicate that NR3C2 may play an important role in BP progression and development of hypertension., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: We used single-marker and novel gene-based methods to examine the associations of endothelial system genes with blood pressure (BP) changes and hypertension in a longitudinal family study., Methods: The Genetic Epidemiology Network of Salt Sensitivity follow-up study was conducted among 1,768 Chinese participants from 633 families. Nine BP measurements were obtained at baseline and at 2 follow-up visits using a random-zero sphygmomanometer. Mixed-effect models were used to assess the additive associations of 206 single-nucleotide polymorphisms (SNPs) in 15 endothelial system genes with longitudinal BP changes and hypertension incidence. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses., Results: Among those free from hypertension at baseline, 512 (32.1%) developed hypertension during the average 7.2 years of follow-up. In single-marker analyses, each copy of the minor alleles of correlated SELE markers rs4656704, rs6427212, and rs5368 were associated with increased risk of developing hypertension (P for trend = 1.48 × 10(-4), 6.69 × 10(-5), and 7.64 × 10(-5), respectively). In addition, the minor allele of SELE marker rs3917436 was associated with smaller diastolic BP (DBP) increases over time. Results of gene-based analyses confirmed associations of the SELE gene with the longitudinal BP phenotypes (P values < 1.00 × 10(-6) for DBP change and hypertension incidence). Furthermore, the DDAH1 and COL18A1 genes were associated with systolic BP change (P < 1.00 × 10(-6) and P = 4.00 × 10(-6), respectively), while EDNRA was associated with hypertension incidence (P = 2.39 × 10(-4))., Conclusions: The current study provides strong evidence of a role of endothelial system genes in BP progression and hypertension incidence., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: We examined the associations of epithelial sodium channel (ENaC) genes with blood pressure (BP) changes and hypertension incidence in a longitudinal family study., Methods: A total of 2,755 Han Chinese participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) baseline examination were eligible for this study. The associations of 43 tag single nucleotide polymorphisms (SNPs) in ENaC genes with BP changes and hypertension incidence were assessed using mixed models to account for the correlations of repeated measures among individuals and within families. A genotype by time interaction term was used to model differences in longitudinal BP change according to genotype over time. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses., Results: During an average of 7.4 years follow-up, systolic BP (SBP) and diastolic BP (DBP) increased, and approximately 33% of participants developed hypertension. SCNN1A SNP rs11064153 and SCNN1G SNP rs4401050 were significantly associated with longitudinal changes in SBP after adjustment for multiple testing (P interaction = 5.8×10(-4) and 0.001, respectively). Similar but nonsignificant trends were observed for the associations between both rs11064153 and rs4401050 and DBP changes (P interaction = 0.024 and 0.005, respectively) and between rs11604153 and hypertension incidence (P = 0.02). Gene-based analyses also supported the overall association of SCNN1G with longitudinal changes in SBP (P = 2.0×10(-4))., Conclusions: Our findings indicated that SCNN1A and SCNN1G may contribute to BP changes over time in the Han Chinese population. Replication of these findings is warranted., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Blood pressure (BP) response to cold pressor test (CPT) is associated with increased risk of cardiovascular disease. We performed a genome-wide linkage scan and regional association analysis to identify genetic determinants of BP response to CPT., Methods and Results: A total of 1961 Chinese participants completed the CPT. Multipoint quantitative trait linkage analysis was performed, followed by single-marker and gene-based analyses of variants in promising linkage regions (logarithm of odds ≥2). A suggestive linkage signal was identified for systolic BP response to CPT at 20p13 to 20p12.3, with a maximum multipoint logarithm of odds score of 2.37. On the basis of regional association analysis with 1351 single nucleotide polymorphisms in the linkage region, we found that marker rs2326373 at 20p13 was significantly associated with mean arterial pressure responses to CPT (P=8.8×10(-6)) after false discovery rate adjustment for multiple comparisons. A similar trend was also observed for systolic BP response (P=0.03) and diastolic BP response (P=4.6×10(-5)). Results of gene-based analyses showed that variants in genes MCM8 and SLC23A2 were associated with systolic BP response to CPT (P=4.0×10(-5) and 2.7×10(-4), respectively), and variants in genes MCM8 and STK35 were associated with mean arterial pressure response to CPT (P=1.5×10(-5) and 5.0×10(-5), respectively)., Conclusions: Within a suggestive linkage region on chromosome 20, we identified a novel variant associated with BP responses to CPT. We also found gene-based associations of MCM8, SLC23A2, and STK35 in this region. Additional work is warranted to confirm these findings., Clinical Trial Registration Url: http://www.clinicaltrials.gov; Unique identifier: NCT00721721., (© 2014 American Heart Association, Inc.)

Objective: To identify chromosomal regions harboring quantitative trait loci for waist circumference (WC) and body mass index (BMI)., Design and Methods: A genome-wide linkage scan and regional association study WC and BMI among 633 Chinese families was conducted., Results: A significant linkage signal for WC was observed at 22q13.31-22q13.33 in the overall analysis (LOD = 3.13). Follow-up association study of 22q13.31-13.33 revealed an association between the TBC1D22A gene marker rs16996195 and WC (false discovery rate [FDR]-Q < 0.05). In gender-stratified analysis, suggestive linkage signals were attained for WC at 2p24.3-2q12.2 and 22q13.33 among females (LOD = 2.54 and 2.15, respectively). Among males, 6q12-6q13 was suggestively linked to BMI (LOD = 2.03). Single marker association analyses at these regions identified male-specific relationships of six single nucleotide polymorphisms (SNPs) at 2p24.3-2q12.2 (rs100955, rs13020676, rs13014034, rs12990515, rs17024325, and rs2192712) and five SNPs at 6q12-6q13 (rs7747318, rs7767301, rs12197115, rs12203049, and rs9454847) with the obesity-related phenotypes (all FDR-Q < 0.05). At chromosome 6q12-6q13, markers rs7755450 and rs11758293 predicted BMI in females (both FDR-Q < 0.05)., Conclusions: Genomic regions on chromosomes 2, 6, and 22 which may harbor important obesity-susceptibility loci were described. Follow-up study of these regions revealed several novel variants associated with obesity related traits. Future work to confirm these promising findings is warranted., (Copyright © 2013 The Obesity Society.)

Background: Blood pressure (BP) responses to dietary sodium and potassium intervention and cold pressor test vary considerably among individuals. We aimed to identify novel genetic variants influencing individuals' BP responses to dietary intervention and cold pressor test., Methods and Results: We conducted a genome-wide association study of BP responses in 1881 Han Chinese and de novo genotyped top findings in 698 Han Chinese. Diet-feeding study included a 7-day low-sodium (51.3 mmol/d), a 7-day high-sodium (307.8 mmol/d), and a 7-day high-sodium plus potassium supplementation (60 mmol/d). Nine BP measurements were obtained during baseline observation and each intervention period. The meta-analyses identified 8 novel loci for BP phenotypes, which physically mapped in or near PRMT6 (P=7.29 × 10(-9)), CDCA7 (P=3.57 × 10(-8)), PIBF1 (P=1.78 × 10(-9)), ARL4C (P=1.86 × 10(-8)), IRAK1BP1 (P=1.44 × 10(-10)), SALL1 (P=7.01 × 10(-13)), TRPM8 (P=2.68 × 10(-8)), and FBXL13 (P=3.74 × 10(-9)). There was a strong dose-response relationship between the number of risk alleles of these independent single-nucleotide polymorphisms and the risk of developing hypertension during the 7.5-year follow-up in the study participants. Compared with those in the lowest quartile of risk alleles, odds ratios (95% confidence intervals) for those in the second, third, and fourth quartiles were 1.39 (0.97, 1.99), 1.72 (1.19, 2.47), and 1.84 (1.29, 2.62), respectively (P=0.0003 for trend)., Conclusions: Our study identified 8 novel loci for BP responses to dietary sodium and potassium intervention and cold pressor test. The effect size of these novel loci on BP phenotypes is much larger than those reported by the previously published studies. Furthermore, these variants predict the risk of developing hypertension among individuals with normal BP at baseline.

Background: We examined the association between 799 single-nucleotide polymorphisms in 39 sex hormone genes and blood pressure (BP) responses to a dietary-sodium intervention., Methods: A 7-day low-sodium feeding study (51.3 mmol sodium/day) followed by a 7-day high-sodium feeding study (307.8 mmol sodium/day) was conducted among 1,906 Han Chinese participants. Nine BP measurements were obtained at baseline and the end of each intervention period using a random-zero sphygmomanometer., Results: Among men, absolute BP responses to sodium interventions decreased with the number of minor alleles of estrogen receptor 1 (ESR1) markers rs9340844, rs9397453, rs9371562, rs9397459, and rs9383951. For example, mean diastolic blood pressure (DBP) responses to low-sodium intervention (95% confidence interval) were -2.67 (-3.13, -2.22) mm Hg among those with the rs9397453 C/C genotype, -1.23 (-1.98, -0.48) mm Hg among those with the C/T genotype, and 0.08 (-2.31, 2.47) mm Hg among those with the T/T genotype (P = 1×10(-4); false discovery rate (FDR)-q = 0.04). Mean DBP responses to high sodium according to the rs9397453 genotypes were 1.46 (1.03, 1.89) mm Hg among those with C/C, 0.19 (-0.54, 0.91) mm Hg among those with C/T, and -1.10 (-2.82, 0.61) mm Hg among those with T/T (P = 2×10(-4); FDR-q = 0.04). Similar trends were noted for the association between these ESR1 variants and SBP responses to the dietary intervention. There were no significant associations between sex hormone gene variants and salt sensitivity in women, with genotype-gender interactions noted for the ESR1 markers that achieved significance in men., Conclusions: We identified strong, consistent associations between ESR1 gene variants and salt sensitivity in men. Our results support a gender-specific role for ESR1 in the etiology of this complex trait.

Background: Genetic determinants of blood pressure (BP) response to potassium, or potassium sensitivity, are largely unknown. We conducted a genome-wide linkage scan and positional candidate gene analysis to identify genetic determinants of potassium sensitivity., Methods and Results: A total of 1906 Han Chinese participants took part in a 7-day high-sodium diet followed by a 7-day high-sodium plus potassium dietary intervention. BP measurements were obtained at baseline and after each intervention using a random-zero sphygmomanometer. Significant linkage signals (logarithm of odds [LOD] score, >3) for BP responses to potassium were detected at chromosomal regions 3q24-q26.1, 3q28, and 11q22.3-q24.3. Maximum multipoint LOD scores of 3.09 at 3q25.2 and 3.41 at 11q23.3 were observed for absolute diastolic BP (DBP) and mean arterial pressure (MAP) responses, respectively. Linkage peaks of 3.56 at 3q25.1 and 3.01 at 11q23.3 for percent DBP response and 3.22 at 3q25.2, 3.01 at 3q28, and 4.48 at 11q23.3 for percent MAP response also were identified. Angiotensin II receptor, type 1 (AGTR1), single-nucleotide polymorphism rs16860760 in the 3q24-q26.1 region was significantly associated with absolute and percent systolic BP responses to potassium (P=0.0008 and P=0.0006, respectively). Absolute (95% CI) systolic BP responses for genotypes C/C, C/T, and T/T were -3.71 (-4.02 to -3.40), -2.62 (-3.38 to -1.85), and 1.03 (-3.73 to 5.79) mm Hg, respectively, and percent responses (95% CI) were -3.07 (-3.33 to -2.80), -2.07 (-2.74 to -1.41), and 0.90 (-3.20 to 4.99), respectively. Similar trends were observed for DBP and MAP responses., Conclusions: Genetic regions on chromosomes 3 and 11 may harbor important susceptibility loci for potassium sensitivity. Furthermore, the AGTR1 gene was a significant predictor of BP responses to potassium intake.

A large proportion of the phenotypic variation in blood pressure (BP) appears to be inherited as a polygenic trait. This study examined the association between 12 single nucleotide polymorphisms (SNPs) in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) and adducin 1 alpha (ADD1) genes and systolic (SBP), diastolic (DBP), and mean arterial (MAP) BP. A total of 3,142 individuals from 636 families were recruited from rural north China, and 2,746 met the eligibility criteria for analysis. BP measurements were obtained using a random-zero sphygmomanometer. Genetic variants were determined using SNPlex assays on an automated DNA Sequencer. A mixed linear model was used to estimate the association between each SNP and BP level. After Bonferroni correction, marker rs4963516 of the GNB3 gene remained significantly associated with DBP (corrected P values = 0.006, 0.007 and 0.002 for co-dominant, additive, and recessive models, respectively) and MAP (corrected P values = 0.02, 0.049, and 0.005, respectively). Compared to carriers of the major A allele, CC homozygotes had higher mean DBP (75.81 +/- 0.62 vs. 73.46 +/- 0.25 mmHg, P = 0.0002) and MAP (91.87 +/- 0.68 vs. 89.42 +/- 0.28 mmHg, P = 0.0004) after adjusting for covariates of age, gender, BMI, study site, and room temperature during BP measurement. In summary, these data support a role for the GNB3 gene in BP regulation in the Chinese population. Future studies aimed at replicating these novel findings are warranted.

Objective: To examine the association between renin-angiotensin-aldosterone system (RAAS) genes and salt sensitivity of blood pressure (BP)., Methods: A 7-day low-sodium dietary intervention followed by a 7-day high-sodium dietary intervention was conducted among 1906 participants living in a rural region of north China where habitual sodium intake is high. BP measurements were obtained at baseline and following each intervention using a random-zero sphygmomanometer., Results: DBP and mean arterial pressure responses increased with the number of rs4524238 A alleles in the angiotensin II receptor type 1 gene. For example, mean DBP responses (95% confidence interval) among those with genotypes G/G, G/A, and A/A were -2.53 (-2.89 to -2.18), -3.49 (-4.13 to -2.86), and -5.78 (-9.51 to -2.06) mmHg, respectively, following the low-sodium intervention (P=0.0008). Carriers of the rare A allele of rs5479 in the hydroxysteroid (11-beta) dehydrogenase 2 gene had decreased DBP responses to low sodium (P=0.00004). Those with the C/A and C/C genotypes had DBP responses of -0.70 (-6.62 to 5.22) and -2.71 (-4.88 to -0.54) mmHg, respectively. X chromosome renin-binding protein gene markers rs1557501 and rs2269372 were associated with SBP response to low sodium in men (P=0.00004 and 0.0001, respectively). SBP responses (95% confidence interval) were -6.13 (-6.68 to -5.58) versus -4.07 (-4.88 to -3.26) and -6.04 (-6.57 to -5.52) versus -3.94 (-4.90 to -2.99) mmHg among men with major versus those with minor alleles of rs1557501 and rs2269372, respectively. Haplotype analyses of these genes supported our single-marker findings., Conclusion: We identified renin-angiotensin-aldosterone system variants that were predictive of salt sensitivity in a Han population with habitually high-sodium intake.

Objective: Although beneficial effects of potassium intake on blood pressure (BP) are well established, little is known about genetic factors that underlie interindividual variability in BP response to dietary potassium. In a previous study, we reported the first evidence for significant heritabilities for BP response in a dietary intervention study in rural Chinese. In this report, we extend our genetic studies to examine associations with polymorphisms in genes in vascular endothelial pathways., Methods: We genotyped study participants for 23 single nucleotide polymorphisms (SNPs) in endothelin 1 (EDN1), nitric oxide synthase 3, and E selectin (SELE). We tested 17 of these SNPs for associations with BP response to potassium supplementation in 1843 participants. Association tests used population-based [generalized estimation equation (GEE)] and family-based (quantitative transmission disequilibrium test) methods, as well as tests for gene-by-gene (GxG) interaction (generalized multifactor dimensionalilty reduction and GEE)., Results: Single SNP analysis identified significant associations for several SNPs in EDN1 with multiple measures of BP response to potassium supplementation. The cumulative effects of the minor EDN1 alleles that showed significant associations were to reduce measures of BP response by 0.5-0.9 mmHg. We found significant evidence for effects of GxG interactions between EDN1 and SELE, even in the absence of individual associations with SELE variants., Conclusion: Our results implicate variability in EDN1 and SELE as genetic factors that influence BP response to potassium intake. Although such epidemiological studies do not allow direct determination of physiologic mechanisms, our findings of joint effects identify EDN1 and SELE as targets for functional studies to determine their interactions in BP response to potassium intake.

Objective: We examined the association between genetic variants in the apelin system and blood pressure (BP) responses to low-sodium and high-sodium interventions in the GenSalt Study., Methods: A 7-day low-sodium intervention (51.3 mmol sodium per day) followed by a 7-day high-sodium intervention (307.8 mmol sodium per day) was conducted among 1906 participants from 637 Han Chinese families. BP measurements were obtained at baseline and following each intervention using a random-zero sphygmomanometer. Twenty-three single nucleotide polymorphisms (SNPs), including both tag and functional SNPs, were selected from three candidate genes (APLN, APLNR, and ACE2). Single marker and haplotype analyses were conducted using the Family Based Association Test program. The false discovery rate method was used to correct for multiple testing., Results: SNPs rs2282623 and rs746886 of the APLNR gene were significantly associated with DBP (both P = 0.002) and mean arterial pressure (MAP) (P = 0.001 and 0.005, respectively) responses to low-sodium intervention. Six SNPs of the ACE2 gene were significantly associated with SBP, DBP, or MAP responses to low-sodium intervention. Three of them, rs1514283, rs1514282, and rs4646176, were also significantly associated with MAP response to high-sodium intervention (all P

Objective: We examined the association between plasma concentrations of high-sensitivity C-reactive protein, soluble intercellular adhesion molecule 1, soluble E-selectin, angiotensin II, renin activity and the risk of hypertension among 2589 study participants aged 20 years and older from Inner Mongolia, China., Methods: Three blood pressure measurements were obtained using a standard mercury sphygmomanometer and hypertension was defined as blood pressure of at least 140/90 mmHg or use of antihypertensive medications. Overnight fasting blood samples were obtained to measure the biomarkers of endothelial dysfunction and inflammation., Results: The average levels of high-sensitivity C-reactive protein (7.5 vs. 5.4 mg/l), soluble intercellular adhesion molecule 1 (339.4 vs. 322.6 ng/ml), soluble E-selectin (19.1 vs. 18.2 ng/ml), and angiotensin II (52.0 vs. 47.0 pg/ml) were significantly higher, whereas renin activity (1.3 vs. 1.5 mg/ml.h) was lower in hypertensive compared to normotensive participants (all P value <0.001). Compared to the lowest quartile, the multivariable-adjusted odds ratios (95% confidence interval) of hypertension for the highest quartile were 1.41 (1.06, 1.86) for high-sensitivity C-reactive protein, 1.93 (1.48, 2.53) for angiotensin II, and 0.70 (0.54, 0.91) for renin activity., Conclusion: Our study indicated that elevated plasma levels of high-sensitivity C-reactive protein and angiotensin II were positively and renin activity inversely associated with the risk of hypertension. These data suggest that inflammation and endothelial dysfunction may play a role in the cause of hypertension.

Background: Hypertension is a major global-health challenge because of its high prevalence and concomitant risks of cardiovascular disease. We estimated premature deaths attributable to increased blood pressure in China., Methods: We did a prospective cohort study in a nationally representative sample of 169,871 Chinese adults aged 40 years and older. Blood pressure and other risk factors were measured at a baseline examination in 1991 and follow-up assessment was done in 1999-2000. Premature death was defined as mortality before age 72 years in men and 75 years in women, which were the average life expectancies in China in 2005. We calculated the numbers of total and premature deaths attributable to blood pressure using population-attributable risk, mortality, and the population size of China in 2005., Findings: Hypertension and prehypertension were significantly associated with increased all-cause and cardiovascular mortality (p<0.0001). We estimated that in 2005, 2.33 million (95% CI 2.21-2.45) cardiovascular deaths were attributable to increased blood pressure in China: 2.11 million (2.03-2.20) in adults with hypertension and 0.22 million (0.19-0.25) in adults with prehypertension. Additionally, 1.27 million (1.18-1.36) premature cardiovascular deaths were attributable to raised blood pressure in China: 1.15 million (1.08-1.22) in adults with hypertension and 0.12 million (0.10-0.14) in adults with prehypertension. Most blood pressure-related deaths were caused by cerebrovascular diseases: 1.86 million (1.76-1.96) total deaths and 1.08 million (1.00-1.15) premature deaths., Interpretation: Increased blood pressure is the leading preventable risk factor for premature mortality in the Chinese general population. Prevention and control of this condition should receive top public-health priority in China., Funding: American Heart Association (USA); National Heart, Lung, and Blood Institute, National Institutes of Health (USA); Ministry of Health (China); and Ministry of Science and Technology (China).

Background: Genetic determinants of blood pressure (BP) responses to the cold pressor test (CPT), a phenotype associated with risk of hypertension and cardiovascular disease has not been well studied., Methods: We examined the heritability of BP response to CPT in 1,994 subjects from 627 families in rural north China. BP was measured before and at 0, 1, 2, and 4 min after the participants immersed their hand in ice water for 1 min. Heritabilities of baseline BP and responses at 0 min, maximum response, and area-under-the-curve (AUC) during CPT were computed using a variance components method. Additionally, bivariate heritabilities were calculated to test the existence of shared genetic determinants between baseline BP and responses to CPT., Results: Heritabilities of baseline BP and responses to CPT were estimated from 14 to 35%, which all significantly differed from 0 (P < or = 0.002). Genetic correlations (s.e.) due to the same genes between baseline BP and responses to CPT ranged from -0.07 (0.14) to 0.21 (0.15), which were not significantly different from 0. Genetic correlations between reactivity and recovery were 0.67 (0.10) and 0.59 (0.10) for systolic (SBP) and diastolic BP (DBP), respectively, which were significantly different from 0., Conclusions: We concluded that (i) baseline BP and BP responses to CPT had strong genetic determinants; (ii) baseline BP and BP response to CPT did not share the same genetic components; and (iii) BP reactivity and recovery shared the same genetic components. These findings may lead to a better understanding of the genetic mechanism of BP responses to CPT.

Background: We examined the association between 12 single-nucleotide polymorphisms (SNPs) in the alpha-adducin (ADD1) and guanine nucleotide binding protein (G protein) beta-polypeptide 3 (GNB3) genes and systolic (SBP), diastolic (DBP), and mean arterial (MAP) pressure responses to salt intake., Methods: A 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day) was conducted among 1,906 Han participants from rural North China. Blood pressure (BP) measurements were obtained at baseline and at the end of each intervention period using a random-zero sphygmomanometer., Results: We identified a significant association between a rare ADD1 variant rs17833172 and SBP, DBP, and MAP responses to high sodium (P values <0.0001) and DBP response to low sodium (P value = 0.002). Participants homozygous for the variant A allele of this marker had SBP, DBP, and MAP responses (95% confidence interval) to high salt of 1.6 (-1.8, 4.9), -0.8 (-5.6, 4.0), and -0.1 (-4.0, 3.9) mm Hg, respectively, vs. corresponding responses of 4.6 (2.5, 6.6), 1.7 (-0.2, 3.6), and 2.7 (0.9, 4.4) mm Hg, respectively, for those who were heterozygous or homozygous for the G allele. In addition, participants with at least one copy of the A allele of SNP rs1129649 of the GNB3 gene had significantly decreased MAP response to low salt compared to homozygotes for the C allele (P value = 0.004) with responses of -3.4 (-3.8, -3.0) vs. -4.2 (-4.6, -3.8) mm Hg, respectively., Conclusions: These data support a role for the ADD1 and GNB3 genes in BP salt sensitivity. Future studies aimed at replicating these novel findings are warranted.

Objective: To examine the excess risks associated with prehypertension and absolute benefit of treatment., Methods: We conducted a prospective cohort study in 169 871 Chinese adults aged 40 years and older. Data on blood pressure and covariables were obtained at a baseline examination in 1991 and follow-up evaluation was conducted in 1999-2000., Results: Compared with normotension (<120/80 mmHg), prehypertension (120-139/80-89 mmHg) was significantly associated with an increased relative risk (95% confidence interval) of cardiovascular disease (CVD) incidence 1.34 (1.27, 1.42) and mortality 1.22 (1.15, 1.30), coronary disease incidence 1.32 (1.16, 1.50) and mortality 1.47 (1.23, 1.75), and stroke incidence 1.72 (1.59, 1.86) and mortality 1.67 (1.50, 1.86). The population-attributable risk associated with prehypertension was 10.6 and 7.1% for CVD incidence and mortality, 9.9 and 13.9% for coronary disease incidence and mortality, and 19.9 and 18.7% for stroke incidence and mortality. The optimal 5-year number-needed-to-treat to prevent a CVD event or death was 53 and 185, 17 and 51, and eight and 22 for prehypertension, stage 1 hypertension, and stage 2 hypertension, respectively. The optimal number-needed-to-treat to prevent a CVD event was significantly smaller in prehypertension patients with a history of CVD or diabetes (34 for incidence and 44 for mortality) compared with those without (115 for incidence and 352 for mortality)., Conclusion: Prehypertension was related to an increased risk of CVD. Treatment of prehypertension among patients with a history of CVD or diabetes was as beneficial as treatment of stage 1 hypertensive patients without a history of CVD or diabetes.

Background: We examined the relationship between hypertension subtype and cardiovascular disease incidence and mortality in Chinese adults., Methods and Results: We conducted a prospective cohort study in a nationally representative sample of 169 871 Chinese men and women aged >or=40 years. Data on systolic (SBP) and diastolic blood pressure (DBP) and other variables were obtained at a baseline examination in 1991 with the use of standard protocols. Follow-up evaluation was conducted in 1999-2000, with a response rate of 93.4%. Hypertension subtypes were defined as combined systolic and diastolic hypertension (SBP >or=140 and DBP >or=90 mm Hg), isolated systolic hypertension (SBP >or=140 and DBP <90 mm Hg), isolated diastolic hypertension (SBP <140 and DBP >or=90 mm Hg), and 2 categories of treated hypertension (SBP <140 and DBP <90 mm Hg or SBP >or=140 and/or DBP >or=90 mm Hg). After participants with missing BP values were excluded, 169 577 adults were included in the analyses. Compared with normotensives, relative risks (95% CIs) of cardiovascular disease incidence and mortality were 2.73 (2.60 to 2.86) and 2.53 (2.39 to 2.68) for combined systolic and diastolic hypertension, 1.78 (1.69 to 1.87) and 1.68 (1.58 to 1.78) for isolated systolic hypertension, 1.59 (1.43 to 1.76) and 1.45 (1.27 to 1.65) for isolated diastolic hypertension, 2.01 (1.64 to 2.48) and 1.61 (1.28 to 2.03) for treated hypertension with SBP <140 and DBP <90 mm Hg, and 3.37 (3.07 to 3.69) and 2.88 (2.60 to 3.19) for treated hypertension with SBP >or=140 and/or DBP >or=90 mm Hg, respectively, after adjustment for important covariables., Conclusions: Our results indicate that all hypertension subtypes are associated with significantly increased risk of cardiovascular disease in Chinese adults. Primary prevention of hypertension should be a public health priority in the Chinese population.

Background and Purpose: We studied the relationship between cigarette smoking and stroke incidence and mortality in the Chinese adult population., Methods: We conducted a prospective cohort study in a nationally representative sample of 169 871 Chinese men and women aged 40 years and older. Data on cigarette smoking and other covariables were collected at a baseline examination in 1991 using a standard protocol. Follow-up evaluation was conducted in 1999 to 2000, with a response rate of 93.4%., Results: During an average of 8.3 years follow-up, a total of 6780 stroke events (3979 fatal strokes) were observed. The multivariate-adjusted relative risks (95% confidence interval) of stroke incidence and mortality associated with present cigarette smoking were 1.28 (1.19 to 1.37) and 1.13 (1.03 to 1.25) in men and 1.25 (1.13 to 1.37) and 1.19 (1.04 to 1.36) in women, respectively. The corresponding population attributable risks were 14.2% and 7.1% in men and 3.1% and 2.4% in women. Compared to never-smokers, the multivariate-adjusted relative risks of stroke incidence (95% confidence interval) were 1.21 (1.12 to 1.31), 1.21 (1.11 to 1.32), and 1.36 (1.25 to 1.47) for those who smoked 1 to 9, 10 to 19, and >/=20 cigarettes per day; and 1.18 (1.09 to 1.28), 1.25 (1.15 to 1.35), and 1.34 (1.24 to 1.44) for those who smoked 1 to 11, 12 to 26, and >26 pack-years, respectively (both P<0.0001 for linear trends)., Conclusions: Our study identified a positive and dose-response relationship between cigarette smoking and risk of stroke. Smoking prevention and cessation programs should be an important strategy for reducing the burden of stroke in Chinese adults.

Objective: To examine the association between blood pressure (BP) and mortality among patients with a history of cardiovascular disease (CVD) in China., Methods: We conducted a prospective cohort study among 4195 CVD patients aged 40 years and older. Data on BP and covariables were obtained at a baseline examination in 1991 and follow-up evaluation was conducted in 1999-2000 using standard protocols., Results: After adjustment for important covariables, a significant and linear relationship was observed between BP level and mortality from CVD and all-causes. For example, compared with those with a systolic BP less than 120 mmHg, patients with a systolic BP of 120-129, 130-139, 140-159, 160-179, and at least 180 mmHg had relative risks (95% confidence interval) of 1.28 (0.92, 1.78), 1.62 (1.19, 2.20), 2.09 (1.58, 2.77), 2.31 (1.73, 3.10), and 2.66 (2.01, 3.53) for CVD mortality, and 1.08 (0.84, 1.38), 1.26 (1.00, 1.60), 1.44 (1.17, 1.79), 1.57 (1.25, 1.96), and 1.86 (1.50, 2.30) for all-cause mortality (both P values < 0.0001 for linear trends), respectively. The relationship between BP and mortality was slightly stronger for systolic BP compared with diastolic BP or pulse pressure. Lowering BP to a normal level in hypertensive patients could prevent 55.5% of CVD mortality and 31.2% of all-cause mortality among individuals with a history of CVD., Conclusion: These data indicate that there is a strong, independent, and positive association between BP and mortality among patients with a history of CVD. Furthermore, lowering of BP should be an important approach for preventing premature deaths in this population.

Chronic obstructive pulmonary disease mortality and risk factors were studied in a nationally representative sample of 169,871 Chinese men and women aged 40 years or older. Baseline data were collected in 1991 by using a standard protocol, and a follow-up evaluation was conducted in 1999-2000, with a response rate of 93.4%. Age-standardized mortality (per 100,000 person-years) was 179.9 for men and 141.3 for women. After adjustment for important covariables, the respective relative risks of chronic obstructive pulmonary disease-related mortality for baseline risk factors in men and women were 2.80 (95% confidence interval (CI): 2.64, 2.98) and 2.71 (95% CI: 2.53, 2.89) for each 10-year increase in age, 0.84 (95% CI: 0.74, 0.95) and 1.44 (95% CI: 1.07, 1.95) for alcohol consumption, 1.18 (95% CI: 1.04, 1.35) and 1.77 (95% CI: 1.45, 2.15) for >/=20 pack-years of smoking, 2.37 (95% CI: 1.91, 2.94) and 2.47 (95% CI: 1.66, 3.67) for non-high-school graduation, 1.57 (95% CI: 1.38, 1.79) and 1.35 (95% CI: 1.17, 1.56) for physical inactivity, 2.66 (95% CI: 2.34, 3.02) and 2.60 (95% CI: 2.25, 3.00) for underweight, 1.39 (95% CI: 1.23, 1.57) and 1.73 (95% CI: 1.50, 2.00) for living in northern China, and 2.14 (95% CI: 1.86, 2.46) and 1.79 (95% CI: 1.55, 2.07) for living in rural China. This study indicated that cigarette smoking, low educational level, physical inactivity, and underweight are important modifiable risk factors for chronic obstructive pulmonary disease-related mortality in China.

Background: We examined the relationship between systolic and diastolic blood pressure (BP) and the incidence of cardiovascular disease (CVD) in a nationally representative cohort of 169,871 men and women > or = 40 years of age in China., Methods: Data on BP and other variables were obtained at a baseline examination in 1991 using standard protocols. Follow-up evaluation was conducted in 1999-2000, with a response rate of 93.4%., Results: After adjustment for age, sex, cigarette smoking, alcohol consumption, physical activity, body mass index, education, geographic region, urbanization, and time-dependent history of diabetes, a strong and linear association between both systolic and diastolic BP and incidence of CVD, coronary heart disease and stroke were observed (all P < 0.0001). For example, the relative risks (95% confidence interval (CI)) of CVD incidence were 1.09 (1.00-1.18), 1.25 (1.16-1.35), 1.49 (1.38-1.62), 2.15 (1.99-2.31), 3.01 (2.78-3.27), and 4.16 (3.84-4.51) for those with systolic/diastolic BP of 110-119/75-79, 120-129/80-84, 130-139/85-89, 140-159/90-99, 160-179/100-109, and > or = 180/110 mm Hg compared to those with BP <110/75 mm Hg. Increases in systolic BP were associated with a greater risk of CVD compared to corresponding increases in diastolic BP. The linear trend for increased CVD risk being related to higher BP levels was observed in all subgroups of gender, age, body weight, and cigarette smoking., Conclusions: Our results indicate that there is a strong, linear, and independent relationship between BP levels and the risk of CVD in Chinese adults. Systolic BP is a stronger predictor of CVD risk compared to diastolic BP.