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1.  Projected Impact of Urbanization on Cardiovascular Disease in China 
Objectives
The Coronary Heart Disease (CHD) Policy Model-China, a national scale cardiovascular disease computer simulation model, was used to project future impact of urbanization.
Methods
Populations and cardiovascular disease incidence rates were stratified into four submodels: North-Urban, South-Urban, North-Rural, and South-Rural. 2010 was the base year, and high and low urbanization rate scenarios were used to project 2030 populations.
Results
Rural-to-urban migration, population growth, and aging were projected to more than double cardiovascular disease events in urban areas and increase by 27.0–45.6% in rural areas. Urbanization is estimated to raise age-standardized coronary heart disease incidence by 73–81 per 100,000 and stroke incidence only slightly.
Conclusions
Rural-to-urban migration will likely be a major demographic driver of the cardiovascular disease epidemic in China.
doi:10.1007/s00038-012-0400-y
PMCID: PMC3465962  PMID: 22918518
urbanization; migration; cardiovascular disease; China
2.  Blood Pressure Responses to Dietary Sodium and Potassium Interventions and the Cold Pressor Test: The GenSalt Replication Study in Rural North China 
BACKGROUND
In the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study, we observed that blood pressure (BP) responses to dietary sodium and potassium interventions and the cold pressor test (CPT) varied greatly among individuals. We conducted a replication study to confirm our previous findings among 695 study participants.
METHODS
The dietary intervention included a 7-day low sodium (51.3 mmol/day), a 7-day high sodium (307.8 mmol/day), and a 7-day high sodium with potassium supplementation (307.8 mmol sodium and 60 mmol potassium/day). BP measurements were obtained during the baseline and each intervention phase. During the CPT, BP was measured before and at 0, 1, 2, and 4 minutes after the participants immersed their right hand in ice water for 1 minute.
RESULTS
Systolic and diastolic BP responses (mean ± SD (range), mm Hg) were 8.1±8.4 (−39.1 to 18.2) and −3.5±5.1 (−25.1 to 11.1) to low sodium, 9.1±8.4 (−13.3 to 33.1) and 4.0±5.4 (−16.0 to 20.7) to high sodium, and −4.6±5.8 (−31.8 to 11.6) and −1.9±4.3 (−16.9 to 14.2) to potassium supplementation, respectively (all P < 0.0001 for comparison with each former phase). The mean maximum systolic and diastolic BP responses to the CPT were 16.5±10.5 (−15.3 to 63.3) and 7.6±6.1 (−8.7 to 39.3), respectively (all P < 0.0001).
CONCLUSIONS
Our study indicates that there are large variations in BP responses to dietary sodium and potassium interventions and to the CPT among individuals.
doi:10.1093/ajh/hpt163
PMCID: PMC3848630  PMID: 24004934
blood pressure; cold pressor test; dietary potassium; hypertension; salt sensitivity; sodium.
3.  Genome-Wide Association Study Identifies Eight Novel Loci Associated with Blood Pressure Responses to Interventions in Han Chinese 
Background
Blood pressure (BP) responses to dietary sodium and potassium intervention and cold pressor test (CPT) vary considerably among individuals. We aimed to identify novel genetic variants influencing individuals’ BP responses to dietary intervention and CPT.
Methods and Results
We conducted a genome-wide association study of BP responses in 1,881 Han Chinese and de novo genotyped top findings in 698 Han Chinese. Diet-feeding study included a 7-day low-sodium (51.3 mmol/day), a 7-day high-sodium (307.8 mmol/day), and a 7-day high-sodium plus potassium-supplementation (60 mmol/day). Nine BP measurements were obtained during baseline observation and each intervention period. The meta-analyses identified eight 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 SNPs and the risk of developing hypertension over 7.5-year follow-up in the study participants. Compared to 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 CPT. The effect size of these novel loci on BP phenotypes are 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.
doi:10.1161/CIRCGENETICS.113.000307
PMCID: PMC3952335  PMID: 24165912
blood pressure; genomics; sodium; potassium
4.  Circulating Adipocytokines and Chronic Kidney Disease 
PLoS ONE  2013;8(10):e76902.
Background
Adipokines have been associated with atherosclerotic heart disease, which shares many common risk factors with chronic kidney disease (CKD), but their relationship with CKD has not been well characterized.
Methods
We investigated the association of plasma leptin, resistin and adiponectin with CKD in 201 patients with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or presence of albuminuria. Quantile regression and logistic regression models were used to examine the association between adipokines and CKD adjusting for multiple confounding factors.
Results
Compared to controls, adjusted median leptin (38.2 vs. 17.2 ng/mL, p<0.0001) and adjusted mean resistin (16.2 vs 9.0 ng/mL, p<0.0001) were significantly higher in CKD cases. The multiple-adjusted odds ratio (95% confidence interval) of CKD comparing the highest tertile to the lower two tertiles was 2.3 (1.1, 4.9) for leptin and 12.7 (6.5, 24.6) for resistin. Median adiponectin was not significantly different in cases and controls, but the odds ratio comparing the highest tertile to the lower two tertiles was significant (1.9; 95% CI, 1.1, 3.6). In addition, higher leptin, resistin, and adiponectin were independently associated with lower eGFR and higher urinary albumin levels.
Conclusions
These findings suggest that adipocytokines are independently and significantly associated with the risk and severity of CKD. Longitudinal studies are warranted to evaluate the prospective relationship of adipocytokines to the development and progression of CKD.
doi:10.1371/journal.pone.0076902
PMCID: PMC3792047  PMID: 24116180
5.  Reproducibility of Blood Pressure Response to the Cold Pressor Test 
American Journal of Epidemiology  2012;176(Suppl 7):S91-S98.
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.
doi:10.1093/aje/kws294
PMCID: PMC3530368  PMID: 23035148
blood pressure; cardiovascular diseases; hypertension; reproducibility of results; stress, physiological
6.  The Association of Plasma Fluorescent Oxidation Products and Chronic Kidney Disease: A Case-Control Study 
American journal of nephrology  2012;36(4):297-304.
Background/Aims
Plasma fluorescent oxidation products (FLOP) constitute a stable and easily-measured biomarker of cumulative oxidative stress. However, its association with chronic kidney disease (CKD) has not been studied.
Methods
We examined the association of FLOP and CKD in 201 CKD patients and 201 controls without CKD from the community. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 or presence of albuminuria.
Results
Adjusted median (interquartile range) of FLOP was significantly higher in patients with CKD than in controls [FLOP1 (lipid oxidation products): 215.2 fluorescent intensity (FI)/mL (181.3, 268.7) vs. 156.6 FI/mL (139.6, 177.3), p<0.0001; FLOP2 (DNA oxidation products): 534.8 FI/mL (379.3, 842.4) vs. 269.9 FI/mL (232.4, 410.5), p<0.0001; FLOP3 (protein and phospholipids oxidation products): 51.4 FI/mL (44.4, 66.0) vs. 45.2 FI/mL (38.3, 51.7), p=0.002]. Compared with those with a FLOP level below the 75th percentile, participants with a FLOP level above the 75th percentile had an increased odds of CKD after adjustment for covariables [FLOP1: odds ratio (OR), 13.1, 95% confidence interval (CI), 6.2, 27.6; FLOP2: OR, 5.7, 95% CI, 2.9, 11.1; FLOP3: OR, 2.4, 95% CI, 1.2, 4.7]. Levels of FLOP1, FLOP2, and FLOP3 were related to eGFR (all p-values <0.0001) and log-transformed urine albumin (all p-values <0.005) in multivariable adjusted linear regression models.
Conclusion
These data indicate that elevated FLOP level is associated with CKD status and severity. Future studies are warranted to elucidate its role in the development and progression of CKD.
doi:10.1159/000342330
PMCID: PMC3557790  PMID: 22986784
albuminuria; biological markers; case-control study; glomerular filtration rate; kidney diseases; oxidative stress
7.  Elevated Plasma Levels of Endostatin Are Associated with Chronic Kidney Disease 
American Journal of Nephrology  2012;35(4):335-340.
Background/Aims
Angiogenesis may play an important role in the renal repair process after injury. We investigated the association between plasma endostatin, an endothelial-specific antiangiogenic factor, and chronic kidney disease (CKD).
Methods
We compared plasma endostatin levels in 201 CKD patients and 201 controls. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or presence of albuminuria (≥30 mg/24 h).
Results
After adjustment for established CKD risk factors, the median (interquartile range) of plasma endostatin was 276.7 ng/dl (199.3–357.5) in patients with CKD and 119.4 ng/dl (103.7–134.6) in controls without CKD (p < 0.0001 for group difference). log-transformed plasma endostatin was significantly and inversely correlated with eGFR (r = −0.83, p < 0.0001) and positively correlated with log-transformed urine albumin (r = 0.66, p < 0.0001) in the study participants. In addition, one standard deviation increase in log-transformed plasma endostatin (0.55 ng/dl) was associated with a decline in eGFR of −26.2 ml/min and an increase in urine albumin of 3.26 mg/ 24 h after adjusting for multiple covariables. Furthermore, the multivariable-adjusted odds ratio for CKD comparing the highest tertile (≥131.4 ng/dl) to the two lower tertiles of plasma endostatin was 21.6 (95% CI: 10.2–45.5; p < 0.0001).
Conclusion
These data indicate that elevated plasma endostatin is strongly and independently associated with CKD. Prospective cohort studies and clinical trials are warranted to further examine the causal relationship between endostatin and risk of CKD and to develop novel interventions targeting circulating endostatin aimed at reducing CKD risk.
doi:10.1159/000336109
PMCID: PMC3362190  PMID: 22456114
Albuminuria; Antiangiogenic factor; Chronic kidney disease; Endostatin; Estimated glomerular filtration rate
8.  Effect of Dietary Protein Supplementation on Blood Pressure: A Randomized Controlled Trial 
Circulation  2011;124(5):589-595.
Background
Observational studies have reported an inverse association between dietary protein intake and blood pressure (BP). We compared the effect of soy protein, milk protein, and carbohydrate supplementation on BP among healthy adults.
Methods and Results
We conducted a randomized double-blind crossover trial with 3-intervention phases among 352 adults with prehypertension or stage-1 hypertension in New Orleans, Louisiana and Jackson, Mississippi from September 2003 to April 2008. The trial participants were assigned to take 40 grams/day of soy protein, milk protein, or carbohydrate supplementation each for 8 weeks in a random order. A 3-week washout period was implemented between the interventions. Three BPs were measured at 2 baseline and 2 termination visits during each of 3 intervention phases using a random-zero sphygmomanometer. Compared to carbohydrate controls, soy protein and milk protein supplementations were significantly associated with −2.0 mmHg (95% confidence interval −3.2 to −0.7, p=0.002) and −2.3 mmHg (−3.7 to −1.0, p=0.0007) net change in systolic BP, respectively. Diastolic BP was also reduced but this change did not reach statistical significance. There was no significant difference in the BP reductions achieved between soy or milk protein supplementation.
Conclusions
The results from this randomized controlled trial indicate that both soy and milk protein intake reduce systolic BP compared to a high glycemic index refined carbohydrate among patients with prehypertension and stage-1 hypertension. Furthermore, these findings suggest that partially replacing carbohydrate with soy or milk protein might be an important component of nutrition intervention strategies for the prevention and treatment of hypertension.
doi:10.1161/CIRCULATIONAHA.110.009159
PMCID: PMC3150301  PMID: 21768541
blood pressure; diet; clinical trials; nutrition; proteins
9.  Formal Public Health Education and Career Outcomes of Medical School Graduates 
PLoS ONE  2012;7(6):e39020.
Background
Few data are available evaluating the associations of formal public health education with long-term career choice and professional outcomes among medical school graduates. The objective of this study was to determine if formal public health education via completion of a masters of public health (MPH) degree among US medical school graduates was associated with early and long-term career choice, professional satisfaction, or research productivity.
Methods
We conducted a retrospective cohort study in 1108 physicians (17.1% completed a MPH degree) who had 10–20 years of follow-up post medical school graduation. Multivariable logistic regression analyses were conducted.
Results
Compared to their counterparts with no MPH, medical school graduates with a MPH were more likely to have completed a generalist primary care residency only [relative risk (RR) 1.79, 95% confidence interval (CI) 1.35–2.29], obtain employment in an academic institution (RR 1.81; 95% CI 1.33–2.37) or government agency (RR 3.26; 95% CI 1.89–5.38), and practice public health (RR 39.84; 95% CI 12.13–107.38) or primary care (RR 1.59; 95% CI 1.18–2.05). Furthermore, medical school graduates with a MPH were more likely to conduct public health research (RR 8.79; 95% CI: 5.20–13.82), receive NIH or other federal funding (RR 3.11, 95% CI 1.74–5.33), have four or more peer-reviewed publications (RR 2.07; 95% CI 1.56–2.60), and have five or more scientific presentations (RR 2.31, 95% CI 1.70–2.98).
Conclusion
Formal public health education via a MPH was associated with career choice and professional outcomes among physicians.
doi:10.1371/journal.pone.0039020
PMCID: PMC3380037  PMID: 22745699
10.  Genetic variants in the renin-angiotensin system and blood pressure reactions to the cold pressor test 
Journal of hypertension  2010;28(12):2422-2428.
Objectives
The purpose of this study was to examine the association between genetic variants in the renin-angiotensin system (RAS) and blood pressure (BP) responses to cold pressor test (CPT).
Methods
The CPT was conducted among 1,998 Han Chinese participants. BP measurements were obtained before and after the CPT using a standard sphygmomanometer according to a standard protocol. The association between SNP genotypes and BP responses to the CPT was assessed using a mixed linear model.
Results
Of 68 SNPs genotyped in 6 RAS genes, two were strongly associated with diastolic BP (DBP) responses to CPT (P ≤ 0.001; false discovery rate q-value < 0.05): rs2006765 and rs943580 in the angiotensinogen (AGT) gene. Compared to C allele carriers of rs2006765, the TT homozygotes had a significantly decreased DBP response to the CPT. For participants with the TT genotype, percent DBP responses were 5.68% (4.25%, 7.10%), compared to corresponding responses of 9.17% (8.66%, 9.68%) among participants with the CC+CT genotype. In addition, SNP rs4681443 of the angiotensin type 1 receptor (AGTR1) gene was significantly associated with percent SBP responses to CPT (P≤0.001; q-value <0.05).
Conclusion
Briefly, our study identified variants in the AGT and AGTR1 genes that may influence BP responses to CPT in Han Chinese population. These results show that genetic variants in the RAS play an important role in BP responses to CPT, and therefore in predicting future hypertension.
doi:10.1097/HJH.0b013e32833ea74e
PMCID: PMC3029492  PMID: 20811292
blood pressure; cold pressor test; renin-angiotensin system; genetics; polymorphism
11.  Association of inflammation and endothelial dysfunction with metabolic syndrome, prediabetes and diabetes in adults from Inner Mongolia, China 
Background
We examined the association of biomarkers of inflammation and endothelial dysfunction with diabetes and metabolic syndrome (MetS) in persons from Inner Mongolia.
Methods
A cross-sectional study was conducted among 2,536 people aged 20 years and older from Inner Mongolia, China. Overnight fasting blood samples were obtained to measure plasma concentrations of high sensitivity C-reactive protein (hsCRP), soluble inter-cellular adhesion molecule-1 (sICAM-1), sE-selectin, angiotensin II, high density lipoprotein cholesterol, triglycerides, and blood glucose. Waist circumference and blood pressure were measured by trained staff. MetS was defined according to the modified ATP III definition for Asians. Elevated level of the biomarker was defined as values in the upper tertile of the distribution. Participants were categorized into one of four groups based on the presence or absence of metabolic and glycemic abnormalities: 1) free of prediabetes, diabetes and MetS (reference group), 2) prediabetes or diabetes only, 3) MetS without prediabetes or diabetes, and 4) MetS plus prediabetes or diabetes. The multivariable models are adjusted for age, gender, smoking, drinking, family history of hypertension, and body mass index.
Results
Among study participants, 18.5% had prediabetes, 3.6% had diabetes, and 27.4% of the entire study population had 3 or more components of the MetS. Elevated hsCRP was associated with an increased odds of prediabetes or diabetes only, MetS without prediabetes or diabetes, and MetS plus prediabetes or diabetes with multivariable adjusted odds ratios (95% confidence intervals) of 2.3 (1.7-3.1), 3.0 (2.4-3.8), and 5.8 (4.5-7.5), respectively. Elevated sICAM-1 was associated with increased odds (95% CI) of prediabetes or diabetes only (2.1, 1.6-2.9) and MetS plus prediabetes or diabetes (4.2, 3.2-5.3) but was not associated with MetS alone. Elevated sE-selectin was associated with a modestly increased risk of MetS (OR 1.7, 95% CI 1.4-2.2). Elevated levels of Angiotensin II were not associated with the MetS plus prediabetes or diabetes in this study.
Conclusions
Diabetes and the MetS are common in the Inner Mongolia population. The biomarkers of inflammation and endothelial dysfunction are associated with increased risk for diabetes and MetS in this population. These results are consistent with results from other populations.
doi:10.1186/1472-6823-11-16
PMCID: PMC3204247  PMID: 21989115
metabolic syndrome; diabetes; inflammation; endothelial dysfunction; C-reactive protein; intercellular adhesion molecule-1; E-selectin
12.  Mortality from suicide and other external cause injuries in China: a prospective cohort study 
BMC Public Health  2011;11:56.
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.
doi:10.1186/1471-2458-11-56
PMCID: PMC3039589  PMID: 21269516
13.  Association of Genetic Variants in the Apelin-APJ System and ACE2 with Blood Pressure Responses to Potassium Supplementation: the GenSalt Study 
American journal of hypertension  2010;23(6):606-613.
BACKGROUND
Genetic factors may influence blood pressure (BP) responses to dietary potassium intake. We examined the association of genetic variants in the apelin-APJ system and angiotensin-converting enzyme 2 (ACE2) with BP responses to potassium supplementation.
METHODS
We conducted a 7-day potassium supplementation (60 mmol/day) intervention among 1,906 Chinese adults who participated in the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Tag single nucleotide polymorphisms (SNPs) based on HapMap data and potential functional SNPs were selected in the APLN, APLNR, and ACE2 genes. Because the ACE2 and APLN genes are located on the X chromosome, men and women were analyzed separately.
RESULTS
In women, SNP rs2235306 in the APLN gene was significantly associated with diastolic BP (DBP) response to potassium supplementation (P=0.0009). The DBP responses [95% confidence interval (CI)] among those with genotypes T/T, T/C, and C/C were −2.22 (−2.74, −1.70), −1.69 (−2.20, −1.19), and −0.81 (−1.54, −0.09) mmHg, respectively. In men, SNP rs4646174 of the ACE2 gene was significantly associated with systolic BP (SBP), DBP, and mean arterial pressure (MAP) responses to potassium supplementation (P=0.0001, P=0.001, and P=3.0×10−6, respectively). The SBP, DBP and MAP responses (95% CI) were −0.79 (−2.27, 0.69) versus −3.53 (−3.94, −3.12), 1.07 (−0.34, 2.49) versus −1.06 (−1.43, −0.69), and 0.44 (−0.60, 1.48) versus −1.89 (−2.22, −1.55) mmHg among men with minor G allele compared to those with major C allele of rs4646174, respectively.
CONCLUSIONS
Our study indicates that genetic variation of APLN and ACE2 may influence BP response to potassium intake.
doi:10.1038/ajh.2010.36
PMCID: PMC2890255  PMID: 20224560
14.  Future cardiovascular disease in China: Markov model and risk factor scenario projections from the Coronary Heart Disease Policy Model-China 
Background
The relative effects of individual and combined risk factor trends on future cardiovascular disease in China have not been quantified in detail.
Methods and Results
Future risk factor trends in China were projected based on prior trends. Cardiovascular disease (coronary heart disease and stroke) in adults ages 35 to 84 years was projected from 2010 to 2030 using the Coronary Heart Disease Policy Model–China, a Markov computer simulation model. With risk factor levels held constant, projected annual cardiovascular events increased by >50% between 2010 and 2030 based on population aging and growth alone. Projected trends in blood pressure, total cholesterol, diabetes (increases), and active smoking (decline) would increase annual cardiovascular disease events by an additional 23%, an increase of approximately 21.3 million cardiovascular events and 7.7 million cardiovascular deaths over 2010 to 2030. Aggressively reducing active smoking in Chinese men to 20% prevalence in 2020 and 10% prevalence in 2030 or reducing mean systolic blood pressure by 3.8 mm Hg in men and women would counteract adverse trends in other risk factors by preventing cardiovascular events and 2.9 to 5.7 million total deaths over 2 decades.
Conclusions
Aging and population growth will increase cardiovascular disease by more than a half over the coming 20 years, and projected unfavorable trends in blood pressure, total cholesterol, diabetes, and body mass index may accelerate the epidemic. National policy aimed at controlling blood pressure, smoking, and other risk factors would counteract the expected future cardiovascular disease epidemic in China.
doi:10.1161/CIRCOUTCOMES.109.910711
PMCID: PMC2937540  PMID: 20442213
China; stroke; coronary heart disease; risk factors; computer modeling
15.  Heritability of Blood Pressure Responses to Cold Pressor Test in a Chinese Population 
American journal of hypertension  2009;22(10):1096-1100.
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 prior to and at 0, 1, 2, and 4 minutes after the participants immersed their hand in ice water for 1 minute. Heritabilities of baseline BP and responses at 0 minutes, maximum response, and area-under-the-curve 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≤0.002). Genetic correlations (standard error) 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 and diastolic BP, respectively, which were significantly different from 0.
CONCLUSIONS
We concluded: 1) baseline BP and BP responses to CPT had strong genetic determinants; 2) baseline BP and BP response to CPT did not share the same genetic components; and 3) 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.
doi:10.1038/ajh.2009.139
PMCID: PMC2896683  PMID: 19661924
blood pressure; heritability; cold pressor test; genetics; hypertension
16.  Gender Difference in Blood Pressure Responses to Dietary Sodium Intervention in the GenSalt Study 
Journal of hypertension  2009;27(1):48-54.
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/day), a 7-day high-salt intervention (307.8 mmol/day), and a 7-day high-salt plus potassium supplementation (60 mmol/day) intervention among 1,906 study participants in rural China. BP was measured 9 times during the 3-day baseline observation and during the last 3 days of each intervention phase using a random-zero sphygmomanometer.
Results
BP responses to low-sodium intervention were significantly greater in women compared to 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 compared to men: 6.4 (5.9 to 6.8) versus 5.2 (4.8 to 5.7) mmHg for systolic and 3.1 (2.7 to 3.5) versus 1.7 (1.4 to 2.1) mmHg for diastolic (all p<0.001). In addition, systolic BP responses to the sodium interventions increased with age and both systolic and diastolic BP responses to the sodium interventions increased with baseline BP levels. BP responses to potassium supplementation also increased with baseline BP levels.
Conclusions
These results suggest that female gender, older age, and hypertension increase sensitivity to dietary sodium intervention. Furthermore, low dietary sodium intake may be more effective in reducing BP among these subgroups.
PMCID: PMC2882679  PMID: 19145767
17.  Cigarette Smoking and Risk of Stroke in the Chinese Adult 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 1999-2000, with a response rate of 93.4%.
Results
During an average of 8.3 years follow-up, a total of 6,780 stroke events (3,979 fatal strokes) were observed. The multivariate-adjusted relative risks (95% confidence interval) of stroke incidence and mortality associated with current cigarette smoking were 1.28 (1.19-1.37) and 1.13 (1.03-1.25) in men and 1.25 (1.13-1.37) and 1.19 (1.04-1.36) 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 (1.12-1.31), 1.21 (1.11-1.32), and 1.36 (1.25-1.47) for those who smoked 1-9, 10-19, and ≥20 cigarettes per day; and 1.18 (1.09-1.28), 1.25 (1.15-1.35), and 1.34 (1.24-1.44) for those who smoked 1-11, 12-26, 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.
doi:10.1161/STROKEAHA.107.505305
PMCID: PMC2881296  PMID: 18323480
smoking; stroke; relative risk; Chinese
18.  Metabolic Syndrome and Salt-Sensitivity of Blood Pressure among Persons without Diabetes 
Lancet  2009;373(9666):829-835.
Summary
Background
We aimed to examine the association between the metabolic syndrome and salt-sensitivity of blood pressure (BP).
Methods
1,906 Chinese aged ≥16 years without diabetes were fed a low-sodium diet (51.3 mmol/day) for 7 days followed by a high-sodium diet (307.8 mmol/day) for an additional 7 days. BP were measured at baseline and at the end of each intervention period using a random-zero sphygmomanometer. Metabolic syndrome was defined as the presence of ≥3 risk factors: abdominal obesity, high triglyceride, low high-density-lipoprotein-cholesterol, elevated BP, and elevated glucose.
Findings
Multivariable-adjusted mean changes (95% confidence intervals) in BP (mmHg) were significantly greater (all p<0.0001) among participants with compared to those without the metabolic syndrome: −7.34 (−8.21, −6.46) versus −5.17 (−5.51, −4.83) for systolic BP and −4.56 (−5.28, −3.85) versus −2.47 (−2.74, −2.19) for diastolic BP during the low-sodium intervention; and 6.51 (5.76, 7.26) versus 4.55 (4.26, 4.84) for systolic BP and 3.25 (2.56, 3.94) versus 1.69 (1.42, 1.96) for diastolic BP during the high-sodium intervention. In addition, compared to those with zero, participants with 4 or 5 risk factors for the metabolic syndrome had a 3.54-fold increased odds (2.05, 6.11) of high salt-sensitivity during the low-sodium intervention and a 3.13-fold increased odds (1.80, 5.43) of high salt-sensitivity during the high-sodium intervention.
Interpretation
These results suggest that the metabolic syndrome significantly enhances BP response to sodium intake. Reduction in sodium intake may be an especially important component in reducing BP among patients with multiple risk factors for the metabolic syndrome.
doi:10.1016/S0140-6736(09)60144-6
PMCID: PMC2822441  PMID: 19223069
blood pressure; metabolic syndrome; dietary sodium; hypertension; salt sensitivity
19.  The future impact of population growth and aging on coronary heart disease in China: projections from the Coronary Heart Disease Policy Model-China 
BMC Public Health  2008;8:394.
Background
China will experience an overall growth and aging of its adult population in coming decades. We used a computer model to forecast the future impact of these demographic changes on coronary heart disease (CHD) in China.
Methods
The CHD Policy Model is a validated state-transition, computer simulation of CHD on a national scale. China-specific CHD risk factor, incidence, case-fatality, and prevalence data were incorporated, and a CHD prediction model was generated from a Chinese cohort study and calibrated to age-specific Chinese mortality rates. Disability-adjusted life years (DALYs) due to CHD were calculated using standard methods. The projected population of China aged 35–84 years was entered, and CHD events, deaths, and DALYs were simulated over 2000–2029. CHD risk factors other than age and case-fatality were held at year 2000 levels. Sensitivity analyses tested uncertainty regarding CHD mortality coding, the proportion of total deaths attributable to CHD, and case-fatality.
Results
We predicted 7.8 million excess CHD events (a 69% increase) and 3.4 million excess CHD deaths (a 64% increase) in the decade 2020–2029 compared with 2000–2009. For 2030, we predicted 71% of almost one million annual CHD deaths will occur in persons ≥65 years old, while 67% of the growing annual burden of CHD death and disability will weigh on adults <65 years old. Substituting alternate CHD mortality assumptions led to 17–20% more predicted CHD deaths over 2000–2029, though the pattern of increases in CHD events and deaths over time remained.
Conclusion
We forecast that absolute numbers of CHD events and deaths will increase dramatically in China over 2010–2029, due to a growing and aging population alone. Recent data suggest CHD risk factor levels are increasing, so our projections may underestimate the extent of the potential CHD epidemic in China.
doi:10.1186/1471-2458-8-394
PMCID: PMC2631484  PMID: 19036167
20.  Association between Blood Pressure Responses to Cold Pressor Test and Dietary Sodium Intervention in the Chinese Population 
Archives of internal medicine  2008;168(16):1740-1746.
Background
Blood pressure (BP) responses to the cold pressor test (CPT) and to dietary sodium intake might be related to the risk of hypertension. We examined the association between BP responses to the CPT and to dietary sodium and potassium interventions.
Methods
The CPT and dietary intervention were conducted among 1,906 study participants in rural China. The dietary intervention included three 7-day periods of low-sodium-feeding (51.3 mmol/day), high-sodium-feeding (307.8 mmol/day), and high-sodium-feeding plus potassium-supplementation (60 mmol/day). A total of 9 BP measurements were obtained during the 3-day baseline observation and the last 3 days of each intervention using a random-zero sphygmomanometer.
Results
BP response to the CPT was significantly associated with BP changes during the sodium and potassium interventions (all p<0.0001). Compared to the lowest quartile of BP response to the CPT, systolic BP changes (95% confident interval) for the top 3 quartiles, respectively, were −2.02 (−2.87, −1.16), −3.17 (−4.05, −2.28), and −5.98 (−6.89, −5.08) mm Hg during the low-sodium intervention. Corresponding systolic BP changes during the high-sodium intervention were 0.40 (−0.36, 1.16), 0.44 (−0.35, 1.22), and 2.30 (1.50, 3.10) mm Hg, and during the potassium-supplementation were −0.26 (−0.99, 0.46), −0.95 (−1.70, −0.20), and −1.59 (−2.36, −0.83) mm Hg, respectively.
Conclusions
These results indicated that BP response to the CPT was associated with salt-sensitivity and potassium-sensitivity. Furthermore, a low-sodium or high-potassium diet might be more effective to lower BP among individuals with high responses to the CPT.
doi:10.1001/archinte.168.16.1740
PMCID: PMC2535851  PMID: 18779460
blood pressure; cold pressor test; dietary sodium; dietary potassium; hypertension; salt sensitivity
21.  Heritability of Blood Pressure Responses to Dietary Sodium and Potassium Intake in Chinese Population 
Hypertension  2007;50(1):116-122.
The heritability of blood pressure responses to dietary intervention has not been well studied. We examined the heritability of blood pressure responses to dietary sodium and potassium intake in a family feeding-study among 1,906 study participants living in rural north China. The dietary intervention included a 7-day low sodium-feeding (51.3 mmol/day), a 7-day high sodium-feeding (307.8 mmol/day), and a 7-day high-sodium plus potassium-supplementation (60 mmol/day). Blood pressure was measured 9 times during the 3-day baseline period preceding the intervention and also during the last 3 days of each intervention phase using a random-zero sphygmomanometer. Heritability was computed using maximum likelihood methods under a variance components model as implemented in the computer program SOLAR. The heritabilities of baseline blood pressure were 0.31 for systolic, 0.32 for diastolic, and 0.34 for mean arterial pressure. The heritabilities increased significantly under dietary intervention and were 0.49, 0.49, and 0.51 during low-sodium, 0.47, 0.49, and 0.51 during high-sodium, and 0.51, 0.52, and 0.53 during potassium-supplementation for systolic, diastolic, and mean arterial pressure, respectively. The heritabilities for percentage blood pressure responses to low-sodium were 0.20, 0.21 and 0.23, to high-sodium were 0.22, 0.33, and 0.33, and to potassium-supplementation were 0.24, 0.21, and 0.25, for systolic, diastolic, and mean arterial pressure, respectively. Our study indicated that the heritabilities of blood pressure under controlled dietary sodium and potassium intake were significantly higher than those under usual diet. In addition, the heritabilities of blood pressure responses to dietary sodium and potassium intake were moderate in this study population.
doi:10.1161/HYPERTENSIONAHA.107.088310
PMCID: PMC2258208  PMID: 17485599
blood pressure; dietary sodium; heritability; potassium supplementation; salt-sensitivity
22.  Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium 
Objective To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians.
Design Pooled analyses of 20 prospective cohorts in Asia, including data from 835 082 east Asians and 289 815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability.
Setting General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh).
Participants 1 124 897 men and women (mean age 53.4 years at baseline).
Main outcome measures Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes.
Results 49 184 cardiovascular deaths (40 791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12).
Conclusions Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.
doi:10.1136/bmj.f5446
PMCID: PMC3788174  PMID: 24473060

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