Serum 25-hydroxyvitamin D deficiency predicts long-term poor prognosis among ischemic stroke patients without hyperglycaemia.

BACKGROUND: It is unclear whether 25-hydroxyvitamin D [25(OH)D] has a protective effect on long-term prognosis of ischemic stroke and whether it is affected by blood glucose levels. We aim to examine the effect of serum vitamin D especially its deficiency on 1-year poor outcome of ischemic stroke patients in total patients and by blood glucose subgroups. METHODS: A total of 3041 ischemic patients from China Antihypertensive Trial in Acute Ischemic Stroke were included. The serum concentrations of 25(OH)D were measured at baseline. All subjects were followed up for death and vascular events at 1year after acute ischemic stroke. RESULTS: Among total ischemic stroke patients and those with hyperglycemia, 25(OH)D deficiency was not associated with the risk of vascular events and death. In the normoglycemic subgroup, 25(OH)D deficiency subjects had a significantly higher risk of poor prognosis compared with those with 25(OH)D≥20ng/ml. The hazard ratio (95% confidence interval) was 1.58(1.04-2.41) in the multivariable adjusted model (P for linear trend=0.02). CONCLUSION: Serum 25(OH)D deficiency may be merely an independent risk factor of 1-year poor prognosis in ischemic stroke patients without hyperglycemia. Future studies about improving long-term prognosis of ischemic stroke by vitamin D supplementation could be first applied to these patients.

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.

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

Reproducibility of blood pressure responses to dietary sodium and potassium interventions: the GenSalt study.

Blood pressure responses to dietary sodium and potassium interventions vary among individuals. We studied the long-term reproducibility of blood pressure responses to dietary sodium and potassium intake. We repeated the dietary sodium and potassium interventions among 487 Chinese adults 4.5 years after the original dietary intervention. The identical dietary intervention protocol, which included a 7-day low-sodium feeding (51.3 mmol/d), a 7-day high-sodium feeding (307.8 mmol/d), and a 7-day high-sodium feeding with oral potassium supplementation (60.0 mmol/d), was applied in both the initial and repeated studies. Three blood pressure measurements were obtained during each of the 3 days of baseline observation and on days 5, 6, and 7 of each intervention period. The results from the 24-hour urinary excretion of sodium and potassium showed excellent compliance with the study diet. Blood pressure responses to dietary intervention in the original and repeated studies were highly correlated. For example, the correlation coefficients (95% confidence interval) for systolic blood pressure levels were 0.77 (0.73-0.80) at baseline, 0.79 (0.75-0.82) during low sodium, 0.80 (0.77-0.83) during high sodium, and 0.82 (0.79-0.85) during high sodium and potassium supplementation interventions (all P<0.0001). The correlation coefficients for systolic blood pressure changes were 0.37 (0.29-0.44) from baseline to low sodium, 0.37 (0.29-0.44) from low to high sodium, and 0.28 (0.20-0.36) from high sodium to high sodium plus potassium supplementation (all P<0.0001). These data indicate that blood pressure responses to dietary sodium and potassium interventions have long-term reproducibility and stable characteristics in the general population.

Association of genetic variants in the apelin-APJ system and ACE2 with blood pressure responses to potassium supplementation: the GenSalt study.

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) mm Hg, 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 x 10(-6), respectively). The SBP, DBP, and MAP responses (95% CI) were -0.79 (-2.27, 0.69) vs. -3.53 (-3.94, -3.12), 1.07 (-0.34, 2.49) vs. -1.06 (-1.43, -0.69), and 0.44 (-0.60, 1.48) vs. -1.89 (-2.22, -1.55) mm Hg among men with minor G allele compared to those with major C allele of rs4646174, respectively. CONCLUSION: Our study indicates that genetic variation of APLN and ACE2 may influence BP response to potassium intake.

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.

Association between blood pressure responses to the cold pressor test and dietary sodium intervention in a Chinese population.

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 1906 study participants in rural China. The dietary intervention included three 7-day periods of low sodium intake (3 g/d of salt [sodium chloride] [51.3 mmol/d of sodium]), high sodium intake (18 g/d of salt [307.8 mmol/d of sodium]), and high sodium intake plus potassium chloride supplementation (60 mmol/d). 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: Blood pressure response to the CPT was significantly associated with BP changes during the sodium and potassium interventions (all P < .001). Compared with the lowest quartile of BP response to the CPT (quartile 1), systolic BP changes (95% confidence intervals) for the quartiles 2, 3, and 4 were -2.02 (-2.87 to -1.16) mm Hg, -3.17 (-4.05 to -2.28) mm Hg, and -5.98 (-6.89 to -5.08) mm Hg, respectively, during the low-sodium intervention. Corresponding systolic BP changes during the high-sodium intervention were 0.40 (-0.36 to 1.16) mm Hg, 0.44 (-0.35 to 1.22) mm Hg, and 2.30 (1.50 to 3.10) mm Hg, respectively, and during the high-sodium plus potassium supplementation intervention were -0.26 (-0.99 to 0.46) mm Hg, -0.95 (-1.70 to -0.20) mm Hg, and -1.59 (-2.36 to -0.83) mm Hg, respectively. CONCLUSIONS: These results indicate 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.

Heritability of blood pressure responses to dietary sodium and potassium intake in a Chinese population.

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 1906 study participants living in rural North China. The dietary intervention included a 7-day low-sodium feeding (51.3 mmol per day), a 7-day high-sodium feeding (307.8 mmol per day), and a 7-day high-sodium plus potassium supplementation (60 mmol per 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 of 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 a usual diet. In addition, the heritabilities of blood pressure responses to dietary sodium and potassium intake were moderate in this study population.