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.
blood pressure; dietary potassium; family history; hypertension
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.
blood pressure; genetics; kallikreins; kinins; polymorphism; sodium, dietary
The effects of low-carbohydrate diets (≤45% of energy from carbohydrates) versus low-fat diets (≤30% of energy from fat) on metabolic risk factors were compared in a meta-analysis of randomized controlled trials. Twenty-three trials from multiple countries with a total of 2,788 participants met the predetermined eligibility criteria (from January 1, 1966 to June 20, 2011) and were included in the analyses. Data abstraction was conducted in duplicate by independent investigators. Both low-carbohydrate and low-fat diets lowered weight and improved metabolic risk factors. Compared with participants on low-fat diets, persons on low-carbohydrate diets experienced a slightly but statistically significantly lower reduction in total cholesterol (2.7 mg/dL; 95% confidence interval: 0.8, 4.6), and low density lipoprotein cholesterol (3.7 mg/dL; 95% confidence interval: 1.0, 6.4), but a greater increase in high density lipoprotein cholesterol (3.3 mg/dL; 95% confidence interval: 1.9, 4.7) and a greater decrease in triglycerides (−14.0 mg/dL; 95% confidence interval: −19.4, −8.7). Reductions in body weight, waist circumference and other metabolic risk factors were not significantly different between the 2 diets. These findings suggest that low-carbohydrate diets are at least as effective as low-fat diets at reducing weight and improving metabolic risk factors. Low-carbohydrate diets could be recommended to obese persons with abnormal metabolic risk factors for the purpose of weight loss. Studies demonstrating long-term effects of low-carbohydrate diets on cardiovascular events were warranted.
carbohydrate-restricted diet; fat-restricted diet; meta-analysis; metabolic syndrome; obesity
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.
allelic association; blood pressure; genetic linkage; salt sensitivity
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.
blood pressure; cardiovascular diseases; hypertension; reproducibility of results; stress, physiological
Rare mutations of the epithelial sodium channel (ENaC) lead to Mendelian forms of salt-sensitive hypertension or salt-wasting hypotension. We aimed to examine the association between common variants in the ENaC genes and salt-sensitivity of blood pressure (BP).
Methods and Results
A total of 1,906 Han Chinese participated in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study, which includes a 7-day low-sodium intake (51.3 mmol sodium/day) followed by a 7-day high-sodium intake (307.8 mmol sodium/day). Nine BP measurements were obtained at baseline and each intervention period using a random-zero sphygmomanometer. Single nucleotide polymorphisms (SNPs), both tagging and functional, from the three ENaC subunits, α, β, and γ (SCNN1A, SCNN1B, and SCNN1G), were genotyped. Multiple common SNPs in SCNN1G were significantly associated with BP response to low-sodium intervention (rs4073930, p=1.7×10-5; rs4073291, p=1.1×10-5; rs7404408, p=1.9×10-5; rs5735, p=3.0×10-4; rs4299163, p=0.004; and rs4499238, p=0.002) even after correcting for multiple testing. For example, under an additive model, the minor allele G of SNP rs4073291 was associated with 1.33 mmHg lower systolic BP (SBP) reduction during low-sodium intervention.
This large dietary sodium intervention study indicates that common variants of ENaC subunits may contribute to the variation of BP response to dietary sodium intake. Future studies are warranted to confirm these findings in an independent population and to identify functional variants for salt-sensitivity.
blood pressure; epithelial sodium channel; genetic variant; salt-sensitivity
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).
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.
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).
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.
blood pressure; cold pressor test; renin-angiotensin system; genetics; polymorphism
Genetic determinants of 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
1,906 Han Chinese participants took part in a 7-day high-sodium followed by a 7-day high-sodium plus potassium dietary intervention. BP measurements were obtained at baseline and following each intervention using a random-zero sphygmomanometer. Significant linkage signals (LOD>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 DBP and 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 were also identified. AGTR1 SNP rs16860760 in the 3q24-q26.1 region was significantly associated with absolute and percent systolic (SBP) responses to potassium (p-values=0.0008 and 0.0006, respectively). Absolute SBP responses (95% CI) for genotypes C/C, C/T, and T/T were: −3.71 (−4.02, −3.40), −2.62 (−3.38, −1.85), and 1.03 (−3.73, 5.79) mmHg, respectively; and percent responses (95% CI) were: −3.07 (−3.33, −2.80), −2.07 (−2.74, −1.41), and 0.90 (−3.20, 4.99), respectively. Similar trends were observed for DBP and MAP responses.
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.
Clinical Trial Registration Information
http://clinicaltrials.gov; Identifier: NCT00721721
blood pressure; potassium; genetics
We examined the association of biomarkers of inflammation and endothelial dysfunction with diabetes and metabolic syndrome (MetS) in persons from Inner Mongolia.
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.
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.
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.
metabolic syndrome; diabetes; inflammation; endothelial dysfunction; C-reactive protein; intercellular adhesion molecule-1; E-selectin
We conducted a meta-analysis of genome-wide association studies of systolic (SBP) and diastolic (DBP) blood pressure in 19,608 subjects of East Asian ancestry from the AGEN-BP consortium followed by de novo genotypingin 2 stages of replication involving 10,518 and 20,247 East Asian samples. We identified novel genome-wide significant (P < 5 × 10−8) associations between SBP or DBP and variants at four novel loci: ST7L-CAPZA1, FIGN-GRB14, ENPEP, and NPR3, as well as a novel variant near TBX3. Except for NPR3, all novel findings were significantly replicated for SBP or DBP in independent samples. Sevenloci previously reported in populations of European descent were confirmed. On 12q24.13, we observed an ethnic specific association(implicating rs671 at the ALDH2 locus as the causal variant) that affected SBP, DBP and multiple traits related to coronary artery disease. These findings provide novel insights into blood pressure regulation and potential targets for intervention.
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.
We genotyped study participants for 23 SNPs in EDN1, NOS3, and SELE. We tested 17 of these SNPs for associations with BP response to potassium supplementation in 1,843 participants. Association tests used population based (GEE) and family based (QTDT) methods, as well as tests for gene by gene interaction (GMDR, GEE).
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 to 0.9 mm Hg. We found significant evidence for effects of gene by gene interactions between EDN1 and SELE, even in the absence of individual associations with SELE variants.
Our results implicate variability in EDN1 and SELE as genetic factors that influence BP response to potassium intake. While 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.
potassium; blood pressure response; dietary intervention; hypertension; genetic association; gene by gene interaction
Results from clinical trials examining the effect of intensive glucose control on cardiovascular disease have been conflicting.
To summarize clinical benefits and harms of intensive versus conventional glucose control for adults with type-2 diabetes.
Studies were retrieved by systematically searching the MEDLINE database (January 1950-April 2009) with no language restrictions.
Two independent reviewers screened abstracts or full text articles to identify randomized trials comparing clinical outcomes in type-2 diabetes patients treated with intensive compared to conventional glucose control.
Two investigators independently abstracted data on study variables and outcomes including severe hypoglycemia, cardiovascular disease, and all-cause mortality.
Five trials involving 27,802 adults were included. Intensive glucose targets were lower in the three most recent trials. Summary analyses showed that, compared with conventional control, intensive glucose control reduced the risk of cardiovascular disease (relative risk (RR): 0.90, 95% confidence interval (CI): 0.83, 0.98; risk difference per 1,000 patients per 5 years (RD): -15, CI: -24, -5) but not cardiovascular death (RR: 0.97, CI: 0.76, 1.24; RD: -3, CI: -14, 7) or all-cause mortality (RR: 0.98, CI: 0.84, 1.15; RD: -4, CI: -17, 10) and increased the risk of severe hypoglycemia (RR: 2.03, CI: 1.46, 2.81; RD: 39, CI: 7, 71). Similar to overall analyses, intensive glucose control reduced risk of cardiovascular disease and increased risk of severe hypoglycemia in pooled findings from early and more recent trials.
Summary rather than individual data were pooled across trials.
Intensive glucose control reduced risk for some cardiovascular disease (e.g., non-fatal myocardial infarction), but did not reduce risk for cardiovascular or all-cause mortality and increased risk of severe hypoglycemia.
intensive glucose control; cardiovascular disease; mortality; relative risk; randomized controlled trials; meta-analysis
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.
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.
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.
Our study indicates that genetic variation of APLN and ACE2 may influence BP response to potassium intake.
We examined the association between genetic variants in the apelin system and blood pressure (BP) responses to low- and high-sodium interventions in the GenSalt Study.
A 7-day low-sodium intervention (51.3 mmol sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day) was conducted among 1,906 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 FBAT program. The false discovery rate method was used to correct for multiple testing.
SNPs rs2282623 and rs746886 of the APLNR gene were significantly associated with diastolic (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 systolic (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 (all P≤0.006). Haplotype analysis indicated the A-T-T haplotype of APLNR SNPs rs721608-rs2282623-rs746886 was associated with decreased DBP and MAP responses to low-sodium intervention (P=0.001 and 0.003, respectively), while G-C-C was associated with increased SBP and MAP responses to high-sodium intervention (P=0.004 and 0.01, respectively).
This large family-based study indicates that genetic variants in the APLNR and ACE2 genes are significantly associated with BP responses to dietary sodium intervention.
ACE2; apelin; apelin receptor; blood pressure; polymorphism; dietary sodium; salt sensitivity
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.
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.
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.
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.
blood pressure; heritability; cold pressor test; genetics; hypertension
To examine the association between renin-angiotensin-aldosterone system (RAAS) genes and salt-sensitivity of blood pressure (BP).
A 7-day low-sodium followed by a 7-day high-sodium dietary intervention was conducted among 1,906 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.
Diastolic BP (DBP) and mean arterial pressure (MAP) responses increased with the number of rs4524238 A alleles in the angiotensin II receptor, type 1 (AGTR1) gene. For example, mean DBP responses (95% CI) among those with genotypes G/G, G/A, and A/A were −2.53 (−2.89, −2.18), −3.49 (−4.13, −2.86), and −5.78 (−9.51, −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 (HSD11B2) gene had decreased DBP responses to low-sodium (p-value=0.00004). Those with the C/A and C/C genotypes had DBP responses of −0.70 (−6.62, 5.22) and −2.71 (−4.88, −0.54) mmHg, respectively. X-chromosome renin-binding protein (RENBP) gene markers rs1557501 and rs2269372 were associated with systolic BP (SBP) response to low-sodium in men (p=0.00004 and 0.0001, respectively). SBP responses (95% CI) were −6.13 (−6.68, −5.58) versus −4.07 (−4.88, −3.26) and −6.04 (−6.57, −5.52) versus −3.94 (−4.90, −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.
We identified RAAS variants that were predictive of salt-sensitivity in a Han population with habitually high-sodium intake.
blood pressure; genetics; polymorphism; dietary sodium; salt sensitivity; renin-angiotensin-aldosterone system
To examine factors related to blood pressure (BP) responses to dietary sodium and potassium interventions.
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.
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.
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.
We examined the association between twelve 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.
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. BP measurements were obtained at baseline and the end of each intervention period using a random-zero sphygmomanometer.
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) mmHg, respectively, versus corresponding responses of 4.6 (2.5, 6.6), 1.7 (−0.2, 3.6), and 2.7 (0.9, 4.4) mmHg, 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) versus −4.2 (−4.6, −3.8) mmHg, respectively.
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.
blood pressure; genetics; polymorphism; dietary sodium; salt sensitivity; ADD1; GNB3
Background and Purpose
We studied the relationship between cigarette smoking and stroke incidence and mortality in the Chinese adult population.
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%.
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).
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.
smoking; stroke; relative risk; Chinese
We aimed to examine the association between the metabolic syndrome and salt-sensitivity of blood pressure (BP).
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.
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.
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.
blood pressure; metabolic syndrome; dietary sodium; hypertension; salt sensitivity
We examined the relationship between hypertension subtype and cardiovascular disease (CVD) 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 40 years and older. Data on systolic (SBP) and diastolic blood pressure (DBP) 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%. Hypertension subtypes were defined as combined systolic and diastolic hypertension (SDH: SBP≥140 and DBP≥90 mm Hg), isolated systolic hypertension (ISH: SBP≥140 and DBP<90 mm Hg), isolated diastolic hypertension (IDH: SBP<140 and DBP≥90 mm Hg), and two categories of treated hypertension (SBP<140 and DBP<90 mm Hg or SBP≥140 and/or DBP≥90 mm Hg). After excluding participants with missing BP values, 169,577 adults were included in the analyses. Compared to normotensives, relative risks (95% confidence interval) of CVD incidence and mortality were 2.73 (2.60–2.86) and 2.53 (2.39–2.68) for SDH, 1.78 (1.69–1.87) and 1.68 (1.58–1.78) for ISH, 1.59 (1.43–1.76) and 1.45 (1.27–1.65) for IDH, 2.01 (1.64–2.48) and 1.61 (1.28–2.03) for treated hypertension with SBP<140 and DBP<90 mm Hg, and 3.37 (3.07–3.69) and 2.88 (2.60–3.19) for treated hypertension with SBP≥140 and/or DBP≥90 mm Hg, respectively, after adjustment for important covariables.
Our results indicate that all hypertension subtypes are associated with significantly increased risk of CVD in Chinese adults. Primary prevention of hypertension should be a public health priority in the Chinese population.
hypertension; cardiovascular disease; relative risk; Chinese
The random-zero sphygmomanometer has been widely used in observational studies and clinical trials for blood pressure measurement. We examined the agreement of blood pressure measurements between random-zero and standard mercury sphygmomanometers among 2,007 Chinese study participants aged 15–60 years. Three blood pressure readings were obtained by trained observers using random-zero and standard mercury sphygmomanometers, respectively, in a random order. Overall, blood pressure readings obtained using the random-zero device were significantly lower than those obtained with the standard mercury sphygmomanometer, with a mean difference ranging from −3.0 to −2.7 mm Hg for systolic and −1.4 to −0.9 mm Hg for diastolic blood pressure (all p <0.01). Correlation coefficients between mean blood pressure measurements obtained using the random-zero and standard mercury sphygmomanometers were high (0.90 for systolic and 0.85 for diastolic blood pressure, both p< 0.0001). In conclusion, our study indicated that there was strong agreement between blood pressure measurements obtained using the random-zero and standard mercury sphygmomanometers although blood pressure values were on average lower with the random-zero sphygmomanometer.
blood pressure measurements; random-zero sphygmomanometer; standard mercury sphygmomanometer; agreement
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.
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.
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.
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.