Jian Feng Huang

Mortality Attributable to Smoking in China

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.

Gender Difference in Blood Pressure Responses to Dietary Sodium Intervention in the GenSalt Study

Objective To examine factors related to blood pressure (BP) responses to dietary sodium and potassium interventions. Methods We conducted a dietary feeding study that included a 7-day low-salt intervention (51.3 mmol sodium/day), a 7-day high-salt intervention (307.8 mmol sodium/day), and a 7-day high-salt and potassium-supplementation (60 mmol potassium/day) intervention among 1906 study participants in rural China. The BP was measured nine times during the 3-day baseline observation and during the last 3 days of each intervention phase using a random-zero sphygmomanometer. Results The BP responses to low-sodium intervention were significantly greater in women than in men: −8.1 [95% confidence interval (−8.6 to −7.6)] versus −7.0 (−7.5 to −6.6) mmHg for systolic and −4.5 (−4.9 to −4.1) versus −3.4 (−3.8 to −3.0) mmHg for diastolic. Likewise, BP responses to high-sodium interventions were significantly greater in women than in men: 6.4 (5.9–6.8) versus 5.2 (4.8–5.7) mmHg for systolic and 3.1 (2.7–3.5) versus 1.7 (1.4–2.1) mmHg for diastolic (all P < 0.001). In addition, systolic BP responses to sodium interventions increased with age, and both systolic and diastolic BP responses to sodium interventions increased with baseline BP levels. BP responses to potassium supplementation also increased with baseline BP levels. Conclusion These results suggest that female gender, older age, and hypertension increase the sensitivity to dietary sodium intervention. Furthermore, low dietary sodium intake may be more effective in reducing BP among these subgroups.

Physical Activity Reduces Salt Sensitivity of Blood Pressure The Genetic Epidemiology Network of Salt Sensitivity Study

Salt sensitivity of blood pressure (BP) is influenced by genetic and environmental factors. A dietary feeding study was conducted from October 2003 to July 2005 that included a 7-day low-sodium intervention (51.3 mmol sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day) among 1,906 individuals who were 16 years of age or older and living in rural northern China. Salt sensitivity of BP was defined as mean BP change from the low-sodium intervention to the high-sodium intervention. Usual physical activity during the past 12 months was assessed at baseline using a standard questionnaire. The multivariable-adjusted means of systolic BP responses to high-sodium intervention were 5.21 mm Hg (95% confidence interval (CI): 4.55, 5.88), 4.97 mm Hg (95% CI: 4.35, 5.59), 5.02 mm Hg (95% CI: 4.38, 5.67), and 3.96 mm Hg (95% CI: 3.29, 4.63) among participants from the lowest to the highest quartiles of physical activity, respectively (P = 0.003 for linear trend). The multivariable-adjusted odds ratio of high salt sensitivity of systolic BP was 0.66 (95% CI: 0.49, 0.88) for persons in the highest quartile of physical activity compared with those in the lowest quartile. Physical activity is significantly, independently, and inversely related to salt sensitivity of BP and may be particularly effective in lowering BP among salt-sensitive individuals.

Genome-wide Linkage and Positional Association Study of Blood Pressure Response to Dietary Sodium Intervention The GenSalt Study

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.

Associations of epithelial sodium channel genes with blood pressure: the GenSalt study

In order to investigate the associations of SCNN1A, SCNN1G and SCNN1B genes with blood pressure (BP) in the Han Chinese population, we included 2880 participants did not use antihypertensive medication in the month prior to the baseline survey in the current analysis. Forty-four tag-single-nucleotide polymorphisms (SNPs) in epithelial sodium channel (ENaC) genes were selected and genotyped, and nine BP measurements were obtained during the 3-day examination. In the single-marker analyses, we identified significant associations of SCNN1A marker rs13306613 with diastolic BP (DBP) and SCNN1B marker rs12447134 with systolic BP (SBP) under codominant model after Bonferroni’s correction (P=2.82 × 10−5 and 4.63 × 10−4, respectively). In addition, five SNPs in SCNN1G and four SNPs in SCNN1B achieved nominal significance for SBP, DBP or mean arterial pressure (MAP) under the additive model. For example, the minor C allele of rs5735 in SCNN1G gene was associated with decreased SBP, DBP and MAP (P=0.016, 5.41 × 10−3 and 4.36 × 10−3, respectively). Gene-based results showed significant associations of SCNN1G and SCNN1B with BP levels. This study suggested that ENaC genes have important roles in BP regulation in the Han Chinese population. Future studies are warranted to replicate these findings, and functional studies are needed to identify true causal variants in ENaC genes.

[OP.1A.11] RESPONSES OF INSULIN AND BLOOD PRESSURE TO DIETARY SODIUM INTERVENTION IN CHINESE POPULATION: THE GENSALT STUDY

Objective: Insulin resistance (IR) is the crucial mechanism for metabolic syndrome, and a risk factor of cardiovascular disease (CVD). Salt restriction is recommended to decrease the risk of CVD. Nevertheless, recent studies have suggested that low sodium intake increases IR. We aimed to examine the association between IR and salt sensitivity of blood pressure (BP) in the GenSalt study. Design and method: We conducted a 7-day low-sodium intervention (51.3 mmol of sodium per day) followed by a 7-day high-sodium intervention (307.8 mmol of sodium per day) in population from the northern rural China. BP measurements were obtained at baseline and each dietary intervention using a random-zero sphygmomanometer. The serum insulin levels were analyzed using an automated two-site radioimmunoassay (Cisbio Bioassays, France). The index of IR was estimated as HOMA-IR = (fasting glucose (mg/dL) X fasting insulin (&mgr;U/mL))/405. Correlations between IR and BP were derived adjusting for age and gender. The associations between insulin response to sodium intervention and BP response to sodium intervention were tested using linear mixed-effect regression model. Results: A total of 1822 participants were included in the final analysis. Fasting serum glucose, insulin and HOMA-IR were higher during low-sodium intervention and lower during high-sodium intervention. The mean glucose, insulin and HOMA-IR were 86.4 mg/dl, 6.1 uIU/ml and 1.3 at baseline, 89.9 mg/dl, 6.4 uIU/ml and 1.4 at the end of low-sodium intervention, 85.3 mg/dl, 5.4 uIU/ml and 1.2 at the end of high-sodium intervention. After adjustment for age and gender, insulin was correlated with BP (SBP: r = 0.15, P < 0.0001; DBP: r = 0.09, P < 0.0001; MAP: r = 0.13, P < 0.0001) at baseline; change in insulin was correlated with BP response (SBP: r = −0.04, P = 0.11; DBP: r = 0.05, P = 0.04; MAP: r = −0.05, P = 0.04) to low-sodium intervention. In linear mixed-effect regression model, the increase in insulin was associated with decrease in SBP (&bgr; = −0.07, p = 0.002), DBP (&bgr; = −0.06, p = 0.03) and MAP (&bgr; = −0.09, p = 0.003) during low-sodium intervention. Conclusions: We concluded that change in inzsulin was significantly associated with BP change during low-sodium intervention. The specific mechanism is not fully understood and further functional studies are warranted to clarify their relationship.