Background Data on the association between serum bilirubin and the risk of stroke are limited and inconclusive. We aimed to evaluate the association between serum bilirubin and the risk of first stroke and to examine any possible effect modifiers in hypertensive patients. Methods and Results Our study was a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). A total of 19 906 hypertensive patients were included in the final analysis. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for the risk of first stroke associated with serum bilirubin levels. The median follow‐up period was 4.5 years. When serum total bilirubin was assessed as tertiles, the adjusted HR of first ischemic stroke for participants in tertile 3 (12.9–34.1 μmol/L) was 0.75 (95% CI, 0.59–0.96), compared with participants in tertile 1 (<9.3 μmol/L). When direct bilirubin was assessed as tertiles, a significantly lower risk of first ischemic stroke was also found in participants in tertile 3 (2.5–24.8 μmol/L) (adjusted HR, 0.77; 95% CI, 0.60–0.98), compared with those in tertile 1 (<1.6 μmol/L). However, there was no significant association between serum total bilirubin (tertile 3 versus 1: adjusted HR, 1.45; 95% CI, 0.89–2.35) or direct bilirubin (tertile 3 versus 1: adjusted HR, 1.27; 95% CI, 0.76–2.11) and first hemorrhagic stroke. Conclusions In this sample of Chinese hypertensive patients, there was a significant inverse association between serum total bilirubin or direct bilirubin and the risk of first ischemic stroke.
Background We aimed to examine the risk factors for renal function decline (RFD) in a community-based cohort of a rural Chinese population with normal kidney function (estimated glomerular filtration rate, eGFR ≥60 mL/min/1.73 m 2 ), both for the population as a whole and stratified by sex. Methods 2518 participants were included in the current analysis. RFD was defined as follows: a drop in the eGFR category accompanied by a 25% or greater drop in eGFR from baseline; or a sustained decline in eGFR of more than 5 mL/min/1.73 m 2 /year. Results The incidence rate of RFD was 8.7% (women 7.4% and men 9.8%). In the multivariable logistic regression model, the ORs (95% CI) of developing RFD was 1.60 (1.01 to 2.54) for men versus women, and 1.51 (1.09 to 2.08) for participants with obesity or abdominal obesity versus none (1.35 (0.85 to 2.14) for men, and 1.65 (1.04 to 2.64) for women). However, prehypertension (OR=1.64; 95% CI 1.02 to 2.63) or hypertension (2.05; 1.21 to 3.47), higher mean blood pressure (≥90 vs <80 mm Hg, 2.63; 1.11 to 6.20), higher pulse pressure (≥50 vs <40 mm Hg, 2.00; 1.26 to 3.18), lower high-density lipoprotein cholesterol (<0.9 vs ≥0.9 mmol/L, 2.65; 1.08 to 6.50) and low physical activity levels (vs high, 3.11; 1.59 to 6.10) were major risk factors for RFD in men. Current smoking (3.22; 1.22 to 2.64) and worse self-reported health (vs better, 2.57; 1.20 to 5.50) were major risk factors for RFD in women. Conclusions Our findings suggested that sex-specific risk factors should be considered in prevention of RFD in the Chinese rural population with normal kidney function.
Abstract Introduction Previous studies in mostly Western populations, have yielded conflicting findings on the association of vitamin B12 with diabetes risk, in part, due to differences in study design and population characteristics. This study sought to examine the vitamin B12 – diabetes association in Chinese hypertensive adults by both cross-sectional and longitudinal analyses. Research Design and Methods This report included a total of 16699 participants from the China Stroke Primary Prevention Trial (CSPPT), with pertinent baseline and follow-up data. Diabetes mellitus (DM) was defined as either physician-diagnosed diabetes, the use of glucose-lowering drugs, or fasting blood glucose (FBG) ≥7.0 mmol/L. New-onset diabetes was defined as any new case of onset diabetes during the follow-up period or fasting blood glucose (FBG) ≥7.0 mmol/L at the exit visit. Results At baseline, there were 1872 (11.2%) diabetic patients; less than 1.5% had clinical B12 deficiency (<148.0 pmol/L). Over a median follow-up period of 4.5 years, there were 1589 (10.7%) cases of new-onset diabetes. Cross-sectional analyses showed a positive association between baseline vitamin B12 levels and FBG levels (β=0.18, 95%CI 0.15-0.21) and diabetes (OR=1.42, 95%CI 1.33-1.51). However, longitudinal analyses showed no association between baseline vitamin B12 and new-onset diabetes or changes in FBG levels. Among a subset of the sample (N=4366) with both baseline and exit B12 measurements, we found a positive association between an increase in B12 and an increase in FBG. Conclusions In this large Chinese hypertensive population mostly sufficient with vitamin B12, parallel cross-sectional and longitudinal analyses provided new insight into the conflicting findings of previous studies, and these results underscore the need for future studies to consider both baseline vitamin B12 and its longitudinal trajectory in order to better elucidate the role of vitamin B12 in the development of diabetes. Such findings, would have important clinical and public health implications.
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Abstract To evaluate the association between plasma retinol levels with all‐cause mortality and investigate the possible effect modifiers in general hypertensive patients with no previous cardiovascular disease (CVD). This case‐control study was nested in the China Stroke Primary Prevention Trial (CSPPT), a randomized, double‐blind, controlled trial conducted in 32 communities in Anhui and Jiangsu provinces in China. The current study included 617 cases of all‐cause mortality and 617 controls matched on age (≤1 year), sex, treatment group, and study site. All‐cause mortality was the main outcome in this analysis, which included death due to any reason. The median follow‐up duration was 4.5 years. Overall, there was a U‐shaped relation of plasma retinol with all‐cause mortality. In the threshold effect analysis, the risk of all‐cause mortality significantly decreased with the increase in plasma retinol (per 10 μg/dL increments: OR, 0.73; 95% CI: 0.61‐0.87) in participants with plasma retinol <58.3 μg/dL and increased with the increase in plasma retinol (per 10 μg/dL increments: OR, 1.08; 95% CI: 1.01‐1.16) in those with plasma retinol ≥58.3 μg/L. In participants with plasma retinol <58.3 μg/dL, a stronger inverse association was observed in those with higher time‐averaged SBP (≥140 vs <140 mm Hg; P ‐interaction = .034), or higher vitamin E levels (≥11.5 [quartile 4]; vs <11.5 μg/mL; P ‐interaction = .013). The present study demonstrated that there was a U‐shaped relationship of plasma retinol levels with the risk of all‐cause mortality in general hypertensive patients, with a turning point around 58.3 μg/dL.
Introduction Previous studies in mostly Western populations have yielded conflicting findings on the association of vitamin B 12 with diabetes risk, in part due to differences in study design and population characteristics. This study sought to examine the vitamin B 12 –diabetes association in Chinese adults with hypertension by both cross-sectional and longitudinal analyses. Research design and methods This report included a total of 16 699 participants from the China Stroke Primary Prevention Trial, with pertinent baseline and follow-up data. Diabetes mellitus was defined as either physician-diagnosed diabetes, use of glucose-lowering drugs, or fasting blood glucose (FBG) ≥7.0 mmol/L. New-onset diabetes was defined as any new case of onset diabetes during the follow-up period or FBG ≥7.0 mmol/L at the exit visit. Results At baseline, there were 1872 (11.2%) patients with diabetes; less than 1.5% had clinical vitamin B 12 deficiency (<148.0 pmol/L). Over a median follow-up period of 4.5 years, there were 1589 (10.7%) cases of new-onset diabetes. Cross-sectional analyses showed a positive association between baseline vitamin B 12 levels and FBG levels (β=0.18, 95% CI 0.15 to 0.21) and diabetes (OR=1.16, 95% CI 1.10 to 1.21). However, longitudinal analyses showed no association between baseline vitamin B 12 and new-onset diabetes or changes in FBG levels. Among a subset of the sample (n=4366) with both baseline and exit vitamin B 12 measurements, we found a positive association between an increase in vitamin B 12 and an increase in FBG. Conclusions In this large Chinese population of patients with hypertension mostly sufficient with vitamin B 12 , parallel cross-sectional and longitudinal analyses provided new insight into the conflicting findings of previous studies, and these results underscore the need for future studies to consider both baseline vitamin B 12 and its longitudinal trajectory in order to better elucidate the role of vitamin B 12 in the development of diabetes. Such findings would have important clinical and public health implications.
The relationship of folic acid supplementation with the risk of cancer remains inconclusive. We aimed to evaluate the effects of folic acid supplementation on cancer incidence among adults with hypertension without history of stroke or myocardial infarction (MI) in the China Stroke Primary Prevention Trial (CSPPT). A total of 20,702 hypertensive adults without history of stroke or MI, stratified by MTHFR C677T genotypes(CC, CT and TT), were randomly assigned to receive double‐blind daily treatment with a single pill containing 10 mg enalapril and 0.8 mg folic acid( n = 10,348) or a pill containing 10 mg enalapril alone( n = 10,354). During a median treatment duration of 4.5 years, cancer occurred in 116 participants(1.12%) in the enalapril‐folic acid group versus 116 participants(1.12%) in the enalapril group (HR, 1.00; 95%CI, 0.77–1.29). There was also no significant difference in the HRs for specific types of cancer(esophageal, gastric, breast, lung, colorectal, head and neck, liver and gynecologic cancer or lymphoma) or cancer mortality(HR, 1.05; 95%CI, 0.69–1.58). For participants not receiving folic acid treatment (enalapril only group), MTHFR 677 TT genotype was an independent predictor of total cancer risk compared to CC genotype (HR, 1.86; 95%CI, 1.07–3.22). Consistently, a beneficial effect was observed in participants with MTHFR TT genotype and low folate levels (<9.0 ng/mL; HR, 0.47; 95%CI, 0.24–0.94). There is no evidence that 0.8 mg daily folic acid supplementation can increase the risk of cancer incidence among adults with hypertension without history of stroke or MI in China. Our data suggest a protective effect in participants with MTHFR TT genotype and low folate levels.