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Background and Aims: While folate is known for its importance in cardiovascular health, it is unknown whether folate status can modify the association between low-density lipoprotein cholesterol (LDL-C) and carotid intima-media thickness (CIMT). We aimed to investigate this question in a Chinese hypertensive population, who are at high-risk of low folate and atherosclerosis.Methods and Results: This report included 14,970 hypertensive adults (mean age 64.5 years; 40.3% male) from the China Stroke Primary Prevention Trial (CSPPT) and analyzed the fasting serum LDL-C and folate, and CIMT data obtained at the last follow-up visit. LDL-C was calculated using the Friedewald equation. Serum folate levels were measured by chemiluminescent immunoassay. CIMT was measured by ultrasound. Non-parametric smoothing plots, multivariate linear regression analysis, subgroup analyses and interaction testing were performed to examine the LDL-C-CIMI relationship and effect modification by folate. Consistent with graphic plots, multivariate linear regression showed that LDL-C levels were independently and positively associated with CIMT (β = 7.69, 95%CI: 5.76-9.62). More importantly, the relationship between LDL-C and CIMT was significantly attenuated with increasing serum folate levels (1st tertile: β = 10.06, 95%CI: 6.67-13.46; 2nd tertile: β = 6.81, 95%CI: 3.55-10.07; 3rd tertile: β = 5.96, 95%CI: 2.55-9.36; P-interaction = 0.045). Subgroup analyses showed the association between LDL-C and CIMT across serum folate tertiles was robust among various strata (all P-interaction >0.05).Conclusions: Among Chinese hypertensive adults, the serum folate levels could modify the association between LDL-C and CIMT. Our findings, if further confirmed, have important clinical implications. [ABSTRACT FROM AUTHOR]

We aimed to examine the association between serum albumin (SAlb) and the development of chronic kidney disease (CKD), and examine any possible effect modifiers in general hypertensive patients with normal renal function and with no previous cardiovascular diseases (CVD). This is a post-hoc analysis (performed at May, 2018) of 12,621 hypertensive adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and SAlb ≥35.0 g/L from the renal sub-study of the China Stroke Primary Prevention Trial (CSPPT), conducted from May 2008 to August 2013. The primary outcome was development of CKD, defined as a decrease in eGFR of ≥30% and to a level of <60 mL/min/1.73 m2; or end stage renal disease. The median follow-up duration was 4.4 years. Overall, the association between SAlb levels and risk of the primary outcome followed a U-shape. The risk of CKD development significantly decreased with the increment of SAlb (per g/L: OR = 0.92; 95% CI: 0.88–0.96) in participants with SAlb <51.4 g/L, and increased with the increment of SAlb (per g/L: OR = 1.06; 95%CI: 1.01–1.11) in participants with SAlb ≥51.4 g/L. Moreover, in participants with SAlb <51.4 g/L, the association between SAlb and CKD development remained significant in participants without proteinuria (per g/L: OR = 0.93; 95% CI: 0.88–0.99). The association between SAlb and CKD development was not significantly modified by age, sex, folic acid treatment, proteinuria, systolic blood pressure (SBP) at baseline and time-averaged SBP during the treatment period (all P -interactions>0.05). There was a U-shaped association between SAlb levels and risk of CKD development among general hypertensive patients with normal renal function and without CVD, with a turning point at about 51.4 g/L. [ABSTRACT FROM AUTHOR]

Evidence from epidemiologic studies on the association of circulating 25-hydroxyvitamin D [25(OH)D] concentrations with the incident risk of cancer has been inconsistent. We aimed to investigate the prospective relationship of baseline plasma 25(OH)D concentrations with the risk of cancer, and to examine possible effect modifiers. We employed a nested case–control study design, including 231 patients with incident cancer during a median 4.5 years of follow up, and 231 matched controls from the China Stroke Primary Prevention Trial (CSPPT). The prevalence of plasma 25(OH)D <15, <20 and <30 ng/mL was 23.6%, 47.4% and 85.5%, respectively. Overall, there was an inverse relation between risk of cancer and plasma 25(OH)D. The Odds ratios (95% CI) for participants in the second (15.1 to <20.6 ng/mL), third (20.6 to <26.4 ng/mL) and fourth quartiles (≥26.4 ng/mL) were 0.45 (95% CI: 0.25–0.80), 0.53 (95% CI: 0.27–1.06) and 0.55 (95% CI: 0.27–1.10), respectively, compared with those in quartile 1. Conversely, low 25(OH)D (<15.1 ng/mL) concentrations were associated with increased risk of cancer (OR, 2.08; 95% CI: 1.20–3.59) compared to higher concentrations. These associations were consistent across subtypes of cancer. Several potential effect modifiers were identified, including plasma vitamin E concentrations and alcohol intake. Low plasma 25(OH)D concentrations (<15.1 ng/mL) were associated with increased total cancer risk among Chinese hypertensive adults, compared to higher 25(OH)D concentrations. This finding and the possible effect modifiers warrant additional investigation. [ABSTRACT FROM AUTHOR]

The relationship of serum phosphate and new-onset hyperuricemia remains uncertain. We aimed to evaluate the relationship of serum phosphate with the risk of new-onset hyperuricemia, and to examine any possible effect modifiers in hypertensive patients. This is a post hoc analysis of the Uric Acid substudy of the CSPPT (China Stroke Primary Prevention Trial). A total of 10 612 participants with normal uric acid levels (<357 μmol/L [6 mg/dL]) at baseline were included in the current study. The primary outcome was new-onset hyperuricemia, which was defined as a uric acid concentration ≥417 μmol/L (7 mg/dL) in men or ≥357 μmol/L (6 mg/dL) in women. During a median follow-up of 4.4 years, 1663 (15.7%) participants developed new-onset hyperuricemia. Overall, there was a significant inverse association between serum phosphate and the risk of new-onset hyperuricemia (per SD increment; odds ratio, 0.71; 95% CI, 0.66-0.76). When serum phosphate was assessed as quartiles, a significantly lower risk of new-onset hyperuricemia was found in participants in quartile 4 (≥1.4 mmol/L; odds ratio, 0.48; 95% CI, 0.40-0.57) compared with those in quartile 1 (<1.2 mmol/L). Similar results were found in males and females. In summary, there was an inverse association between serum phosphate and the risk of new-onset hyperuricemia in hypertensive adults. [ABSTRACT FROM AUTHOR]

We aimed to test the hypothesis that treatment with enalapril and folic acid is more effective in preventing new-onset proteinuria than enalapril alone among hypertensive patients. This is a post hoc analysis of the renal substudy of the CSPPT (China Stroke Primary Prevention Trial). A total of 13 071 eligible participants without proteinuria were randomized to receive a double-blind daily treatment of a single tablet containing 10-mg enalapril and 0.8-mg folic acid (n=6511) or 10-mg enalapril alone (n=6560). The primary outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. Secondary outcomes included a composite of the primary outcome and all-cause death and the annual rate of estimated glomerular filtration rate decline. After a median 4.4 years of treatment, the primary event occurred in 213 (3.9%) and 188 (3.5%) participants, respectively, in the enalapril and the enalapril-folic acid group (odds ratio, 0.90; 95% confidence interval, 0.74-1.11). However, among participants with diabetes mellitus at baseline, folic acid therapy resulted in a significant reduction in the risk for the primary event (3.7% in the enalapril-folic acid group versus 7.4% in the enalapril group; odds ratio, 0.48; 95% confidence interval, 0.29-0.81) and the composite event (odds ratio, 0.62; 95% confidence interval, 0.42-0.92) and a 55% slower annual rate of estimated glomerular filtration rate decline (0.5% versus 1.1% per year; P=0.002). Among those without diabetes mellitus at baseline, there were no between-group differences in all the outcomes. In conclusion, enalapril-folic acid therapy, compared with enalapril alone, significantly reduced the development of proteinuria in diabetic patients with hypertension.Clinical Trial Registration: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00794885. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: We aimed to examine the prevalence of obesity, abdominal obesity and associated factors in 17,656 Chinese hypertensive adults aged 45–75 years. Methods: A cross-sectional investigation was carried out in Lianyungang, China. Overweight or obesity was defined as a body mass index of ≥25kg/m2. Abdominal obesity was defined as a waist circumference ≥90cm for men and ≥80cm for women. Results: The prevalence of overweight or obesity and abdominal obesity was 54.4% (women 59.3% and men 46.0%) and 59.4% (women 73.8% and men 35.1%), respectively. In the multivariable logistic-regression models, higher hypertension grades and standard of living, greater red meat consumption, lower physical activity levels, and antihypertensive treatment were independently associated with overweight or obesity and abdominal obesity in both sexes. Inland residence (versus coastal) was an independent associated factor for abdominal obesity in both sexes. Furthermore, a positive family history of diabetes in both sexes, a positive family history of hypertension, men with a positive family history of coronary heart disease, and men with inland residence were all independently associated with overweight or obesity. Conclusions: We found a high prevalence of overweight or obesity and abdominal obesity in Chinese hypertensive adults, particularly in inland areas. [Copyright &y& Elsevier]

Abstract: This study investigated whether high central adiposity was associated with prediabetes and decreased insulin sensitivity (IS) in both normal-weight (body mass index [BMI] <23 kg/m2) and overweight (BMI ≥23 kg/m2) rural Chinese women. Adipose variables measured by dual-energy x-ray absorptiometry (percentage body fat, percentage lower-body fat [%LF], and percentage trunk fat [%TF]) and general adipose variables (BMI and waist circumference) were used for examining the association of adiposity with prediabetes among 4071 rural Chinese women aged 20 to 60 years. Furthermore, the association of adiposity with IS was tested in both normal- and overweight women with normal glucose tolerance. BMI was highly correlated with percentage body fat and waist circumference, but was weakly correlated with %LF and %TF. Both high %TF (top quartile of %TF) and low %LF (lower 3 quartiles of %LF) were associated with higher prevalence of prediabetes in both normal- and overweight women. Compared with normal-weight women in low %TF, the odds of prediabetes were similarly increased for women with high %TF regardless of whether they were overweight (odds ratio [95% confidence interval] = 1.6 [1.3-2.0]) or not (odds ratio [95% confidence interval] = 1.5 [1.2-2.0]). Similarly, among 3280 women with normal glucose tolerance, high %TF was associated with increased fasting insulin, 2-hour oral glucose tolerance test insulin, and homeostasis model assessment of insulin resistance regardless of weight status (normal or overweight). Among relatively lean, rural Chinese women, high %TF was associated with increased odds of prediabetes and lower IS regardless of weight status (normal or overweight). [Copyright &y& Elsevier]