Deciphering the folate puzzle: Unraveling the impact of genetic variations and metabolites on cancer risk.

The C677T polymorphism in the MTHFR gene and its role in folate metabolism, impacting serum folate metabolites like THF and 5-MTHF, is a critical but underexplored area in cancer research. This nested case-control study utilized data from CHHRS, involving 87,492 hypertensive adults without prior cancer. During a median of 2.02 years, we identified 1332 cancer cases and matched controls based on age, sex, and residency. Serum levels of folate, THF, and 5-MTHF were measured, and the MTHFR C677T gene polymorphism was considered. Statistical analyses included restricted cubic spline regression and conditional logistic regression models. Serum THF levels were inversely associated with overall cancer risk (ORper SD = 0.90, 95% CI = 0.82-0.99), while 5-MTHF levels showed a negative association in the general cohort (ORQ3 vs. Q1 = 0.76, 95% CI = 0.60-0.96; ORQ4 vs. Q1 = 0.75, 95% CI = 0.58-0.98) and in individuals with MTHFR C677T (CC + CT) polymorphism (ORper SD = 0.87, 95% CI = 0.77-0.99; ORQ4 VS. Q1 = 0.79, 95% CI = 0.61-0.98), but a positive association in the MTHFR C677T (TT) subgroup (ORper SD = 1.89, 95% CI = 1.02-3.72; ORQ4 VS. Q1 = 2.17, 95% CI = 1.06-8.21). The impact of folate, THF, and 5-MTHF on cancer risk varied significantly across different cancer types and MTHFR C677T genotypes. This study provides novel insights into the variable effects of folate and its metabolites on cancer risk, influenced by genetic factors like the MTHFR C677T polymorphism and cancer type.

A Negative Association between Plasma Phylloquinone and All-Cause Mortality in Chinese Adults with Hypertension: A Nested Case-Control Study.

BACKGROUND: Previous studies have revealed that vitamin K is essential for preventing various chronic diseases. Phylloquinone is the primary dietary and circulating form of vitamin K. However, data concerning the association between plasma phylloquinone and all-cause mortality are limited. OBJECTIVES: This study aimed to evaluate the association between plasma phylloquinone and risk of all-cause mortality and examine some potential confounders. METHODS: This study is a post hoc analysis of the RCT and a nested, case-control design was used. Enrolled participants had to have hypertension at baseline. Study initiation was 19 May, 2008, and the median follow-up was 4.5 y. A total of 604 mortality cases and 604 controls matched for age, sex, treatment group, and study site were included in this study. Odds ratios (OR) and 95% confidence intervals (CIs) of all-cause mortality were calculated using conditional or unconditional logistic regression, without or with adjusting for pertinent covariates, respectively. The concentration of phylloquinone was measured by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). RESULTS: The mean and median phylloquinone levels were 1.62 nmol/L and 0.89 nmol/L, respectively. There was a significant negative association between log-transformed plasma phylloquinone and all-cause mortality after controlling for potential confounders (per 1 unit increase-OR: 0.79; 95% CI: 0.66, 0.95). Furthermore, the association of plasma phylloquinone with risk of all-cause mortality differed by body mass index (BMI) (<25 kg/m2 compared with ≥25 kg/m2, P-interaction = 0.004). A significant trend of decreasing risk with increasing concentration of phylloquinone was observed in participants with higher BMI (per 1 unit increase-OR: 0.71; 95% CI: 0.56, 0.90; P = 0.004). No significant correlation was found between phylloquinone and risk of all-cause mortality in those with BMI <25 kg/m2. CONCLUSIONS: In Chinese patients with hypertension, there was a significant negative association between baseline plasma phylloquinone and all-cause mortality, especially among those with higher BMI.

Long daytime napping: A silent danger for hypertensive individuals.

BACKGROUND AND PURPOSE: Hypertension significantly contributes to stroke. Previous research has indicated a connection between daytime napping and stroke. Research on the connection between daytime napping duration and first stroke in hypertensive individuals is lacking nevertheless. METHODS: This research, which ran from 24 August 2013 to 31 December 2022, recruited 11,252 individuals with hypertension and without a history of stroke from the China Stroke Primary Prevention Trial. To determine the relationship between daytime napping duration and stroke onset in hypertensive individuals, we conducted analyses for threshold effects, multivariate-adjusted Cox proportional hazard regression models, and Kaplan-Meier survival curves. RESULTS: The duration of daytime napping (<75 min) was positively correlated with stroke risk; beyond 75 min, the risk did not increase further. When compared to hypertensive individuals who napped for 1-30 min, daytime napping 31-60 min (hazard ratio [HR] = 1.27, 95% confidence interval [CI] = 1.06-1.53) and >60 min (HR = 1.37, 95% CI = 1.14-1.65) were substantially related with a greater risk of first stroke. Additionally, this correlation was absent in cases of hemorrhagic stroke, but present in cases of ischemic stroke, specifically for hypertensive individuals who napped for 31-60 min or >60 min (p < 0.05). Kaplan-Meier survival curves displayed that hypertensive individuals who extended daytime napping had an elevated incidence of stroke. CONCLUSIONS: Hypertensive individuals who take longer daytime naps (>30 min) are at an elevated risk of stroke onset, particularly ischemic stroke, irrespective of other factors.

Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy).

BACKGROUND: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. METHODS: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. RESULTS: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. CONCLUSIONS: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. GOV IDENTIFIER: NCT03472508 (Registration Date: March 21, 2018).

Serum total folate, 5-methyltetrahydrofolate and vitamin B12 concentrations on incident risk of lung cancer.

Tobacco smoking is a major known risk factor for lung cancer. While micronutrients, especially those involved in maintaining DNA integrity and regulating gene expression, may be protective, research on this association is limited. This report aimed to investigate associations of total folate, 5-methyltetrahydrofolate (5-mTHF) and vitamin B12 with incident risk of lung cancer, and whether the associations vary by smoking status. A nested case-control study with 490 incident lung cancer cases and 490 controls matched by age (±1 year), sex, residence, and center, drawn from a community-based prospective study in China, was conducted from 2016 to 2019. 5-mTHF accounted for the majority of total folate. Only 4.4% had detectable unmetabolized folic acid. Lung cancer cases had lower levels of 5-mTHF compared to controls. There was an inverse, nonlinear association between 5-mTHF and lung cancer, which persisted after adjustment for covariables (P for trend = .001). Compared to the lowest 5-mTHF quartile, those in higher quartiles had lower risks of lung cancer: second quartile OR = 0.65; 95% CI: 0.45-0.93; third quartile OR = 0.50; 95% CI: 0.34-0.74; fourth quartile OR = 0.56; 95% CI: 0.38-0.83. This inverse association was more pronounced among ever smokers; consistently, the highest risk of lung cancer (OR = 3.21, 95% CI: 1.97-5.24) was observed among ever smokers with low 5-mTHF levels compared to participants who never smoked and had higher 5-mTHF levels. Vitamin B12 was not associated with lung cancer risk. In this sample of Chinese adults without confounding by unmetabolized folic acid, higher levels of 5-mTHF were associated with lower risk of incident lung cancer.

Inverse Association Between Baseline Plasma Selenium Concentrations and Risks of Renal Function Decline in Hypertensive Adults.

BACKGROUND: The kidney has the highest level of selenium (Se) in the body, but the role of plasma Se in chronic kidney disease is uncertain. OBJECTIVE: We aimed to investigate the longitudinal association between baseline plasma Se and renal function decline in adults with hypertension and to explore possible effect modifiers. METHODS: This was a post hoc analysis of 935 men and women with hypertension aged 40 to 75 years from a folic-acid intervention trial (the China Stroke Primary Prevention Trial) in China. The baseline plasma Se was analyzed both as a continuous variable and as tertiles. The primary outcome was a rapid decline in renal function, defined as a mean decline in the estimated glomerular filtration rate of ≥ 5 mL/(min × 1.73 m2) per year. RESULTS: The median follow-up duration from baseline to outcome was 4.4 years. After multivariate adjustment, there was an inverse association between plasma Se and a rapid decline in renal function (per 10-unit increment; OR: 0.85; 95% CI: 0.73, 0.99). When the baseline plasma Se was assessed as tertiles, compared to the lowest tertile (<74.5 µg/L), a lower trend of the primary outcome was found in the second tertile (74.5 to < 89.4 µg/L; OR: 0.60; 95% CI: 0.34, 1.07) and the highest tertile (89.4 to <150 µg/L; OR: 0.42; 95% CI: 0.22, 0.80; Ptrend = 0.006). Furthermore, the Se-renal association was more pronounced among participants with folic acid treatment or with a higher baseline folate concentration (both Pinteraction values < 0.05). CONCLUSIONS: In this sample of Chinese adults with hypertension, baseline plasma Se concentrations were inversely associated with the risk of renal function decline. The China Stroke Primary Prevention Trial was registered at clinicaltrials.gov as NCT00794885.

Change in the Estimated Glomerular Filtration Rate Over Time and Risk of First Stroke in Hypertensive Patients.

BACKGROUND: The association between changes in estimated glomerular filtration rate (eGFR) over time and the risk of stroke remains inconclusive. We aimed to evaluate the relation of eGFR change during the China Stroke Primary Prevention Trial (CSPPT) with the risk of first stroke during the subsequent post-trial follow-up. METHODS: A total of 11,742 hypertensive participants with two eGFR measurements (median measure interval, 4.4; interquartile range, 4.2-4.6 years) and without a history of stroke from the CSPPT were included in this analysis. RESULTS: Over a median post-trial follow-up of 4.4 years, 729 first strokes were identified, of which 635 were ischemic, 88 were hemorrhagic, and 6 were uncertain types of strokes. Compared with those with 1 to <2% per year increase in eGFR (with the lowest stroke risk), those with an increase in eGFR of ≥4% per year had significantly increased risks of first stroke (adjusted hazard ratio [HR] 1.96; 95% confidence interval [CI], 1.10-3.50) and first ischemic stroke (adjusted HR 2.14; 95% CI, 1.17-3.90). Similarly, those with a decline in eGFR of ≥5% per year also had significantly increased first stroke (adjusted HR 2.13; 95% CI, 1.37-3.31) and first ischemic stroke (adjusted HR 1.89; 95% CI, 1.19-3.02) risk. However, there was no significant association between eGFR change and first hemorrhagic stroke. A similar result was found when the change in eGFR was quantified as an absolute annual change. CONCLUSION: In Chinese hypertensive patients, both the decline and increase of eGFR levels were independently associated with the risks of first stroke or first ischemic stroke.

Positive correlation between hypertensive retinopathy and albuminuria in hypertensive adults.

PURPOSE: We investigated the association between albuminuria and hypertensive retinopathy (HR) in hypertensive adults. METHODS: This was a cross-sectional subgroup analysis of data from the China Stroke Primary Prevention Trial. We enrolled 2,964 hypertensive adults in this study. Keith-Wagener-Barker stages was used to assess HR. The urinary albumin to creatinine ratio (UACR) was calculated to evaluate albuminuria. RESULTS: HR was found in 76.6% (n = 2, 271) of the participants, albuminuria was found in 11.1% (n = 330). The UACR levels were significantly higher in subjects with HR than in those without HR (grade 1, ß = 1.42, 95% confidence intervals [CI]: -0.12, 2.95, p = 0.070; grade 2, ß = 2.62, 95% CI: 0.56, 4.67, p = 0.013; grade 3, ß = 5.17, 95% CI: 1.13, 9.20, p = 0.012). In the subgroup analyses, the association between HR and UACR was stronger in current smokers (p for interaction = 0.014). The correlation between HR grades 1 and 2 and UACR was stronger in subjects with higher triglyceride levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglycerides levels (< 1.7 mmol/L, p for interaction = 0.023). The odds of albuminuria were significantly higher in subjects with HR than in those without HR (grade 1, odds ratio [OR] = 1.57, 95% CI: 1.08, 2.29, p = 0.019; grade 2, OR = 2.02, 95% CI: 1.28, 3.18, p = 0.002; grade 3, OR = 2.12, 95% CI: 0.99, 4.55, p = 0.053). In the subgroup analyses, the association between HR grades 1 and 2 and albuminuria was stronger in subjects with higher triglycerides levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglyceride levels (< 1.7 mmol/L, p for interaction = 0.014). CONCLUSION: HR was positively correlated with albuminuria in hypertensive Chinese adults. This correlation was more remarkable when the population was stratified by triglycerides levels and smoking status. HR can be used as an indicator of early renal injury.

Serum L-Carnitine Levels Are Associated With First Stroke in Chinese Adults With Hypertension.

BACKGROUND: This study aimed to evaluate the association of serum L-carnitine with first stroke and explore potential effect modifiers. METHODS: This is a nested, case-control study drawn from the China Stroke Primary Prevention Trial among rural Chinese adults with hypertension, including 557 first stroke cases and 557 age-matched, sex-matched, treatment group-matched, and residence-matched controls. Serum L-carnitine was measured by liquid chromatography with tandem quadrupole mass spectrometry. Multiple conditional logistic regression models were used to evaluate the association between L-carnitine and first stroke. RESULTS: The mean level of serum L-carnitine in the stroke population was 4.7 µg/mL, which was significantly lower than that of the control group (5.7 µg/mL). When L-carnitine was assessed as quintiles, compared with the reference group (quintile 1, <3.3 µg/mL), the odds of stroke were 0.62 (95% CI, 0.39-1.00) in quintile 2, 0.66 (95% CI, 0.40-1.10) in quintile 3, 0.47 (95% CI, 0.28-0.81) in quintile 4, and 0.50 (95% CI, 0.30-0.84) in quintile 5. The trend test was significant (P=0.01). When quintiles 2 to 5 were combined, the adjusted odds ratio of first stroke was 0.58 (95% CI, 0.38-0.87) compared with quintile 1. Similar associations were found for ischemic stroke and hemorrhagic stroke. In subgroup analysis, a significant L-carnitine-stroke association was only observed in the normal folate group (P interaction, 0.039) and in the MTHFR CC genotype group (P interaction, 0.047). CONCLUSIONS: In this study of rural Chinese adults with hypertension, serum L-carnitine had an inverse but nonlinear association with first stroke. Folate status and the MTHFR C677T variant were significant effect modifiers of the association.

Self-Perceived Psychological Stress and Risk of First Stroke in Treated Hypertensive Patients.

OBJECTIVE: We aimed to investigate the prospective association between self-perceived psychological stress and first stroke, and to examine possible effect modifiers among adults with hypertension. METHODS: A total of 20,688 hypertensive adults with information on self-perceived psychological stress at baseline were included from the China Stroke Primary Prevention Trial. Participants were randomly assigned to a double-blind treatment of receiving a single tablet daily with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. Follow-up visits occurred every 3 months after randomization. Psychological stress was measured with a one-item 3-point rating scale. The primary outcome was first stroke (fatal or nonfatal). RESULTS: The median treatment period was 4.5 years. Compared with participants with low levels of psychological stress, those with high psychological stress had a significantly higher risk of first stroke (adjusted hazard ratio = 1.40, 95% confidence interval = 1.01 to 1.94) or first ischemic stroke (adjusted hazard ratio = 1.45; 95% confidence interval = 1.01 to 2.09). Moreover, a stronger positive relationship between psychological stress and first stroke was found in participants with time-averaged mean arterial pressure <101 mm Hg (median; p-interaction = .004) during the treatment period. However, our study did not find a significant association between psychological stress and first hemorrhagic stroke. CONCLUSIONS: Higher psychological stress was associated with an increased risk of first stroke among treated hypertensive patients, especially in those with lower mean arterial pressure during the treatment period.

Inverse Association between Plasma Phylloquinone and Risk of Ischemic Stroke in Chinese Adults with Hypertension and High BMI: A Nested Case-Control Study.

BACKGROUND: Evidence on the association between phylloquinone status and cardiovascular diseases is scarce and conflicting. These inconsistencies may be due to differences in individual characteristics of the study populations, which may modify the association. OBJECTIVE: This study aimed to evaluate the association between plasma phylloquinone and the risk of first total stroke and its subtypes, and to examine potential effect modifications by BMI in patients with hypertension. METHODS: We performed a nested case-control study including 604 first stroke cases and 604 matched controls. The mean age was 62.2 y (range, 45 to 75). Lower BMI was defined as <25 kg/m2  and higher BMI was defined as ≥25 kg/m2. The risks of the first stroke were estimated by ORs and 95% CIs using conditional logistic regression. The primary outcome was total stroke or ischemic stroke. RESULTS: The relation between log-transformed phylloquinone concentration and stroke or ischemic stroke was modified by BMI. Higher phylloquinone concentrations were associated with lower stroke risk in those with a higher BMI. When plasma phylloquinone was assessed as tertiles, the adjusted ORs of first stroke and ischemic stroke for participants with a high BMI in tertile 2-3 were 0.70 (95% CI: 0.46, 1.08) and 0.57 (95% CI: 0.35, 0.92) compared with those in tertile 1, respectively. However, there was no significant association between plasma phylloquinone and risk of first total stroke or ischemic stroke for those with a lower BMI. Patients with a higher BMI and lower phylloquinone concentrations had the highest risk of ischemic stroke and showed a statistically significant difference compared with the reference group with a lower BMI and higher phylloquinone (OR = 1.80, 95% CI: 1.06, 3.10; P-interaction: 0.017). CONCLUSIONS: In Chinese patients with hypertension, there was an inverse association between baseline plasma phylloquinone and risk of first ischemic stroke among those with a higher BMI. This trial was registered at clinicaltrials.gov as NCT00794885.

Joint Associations between Plasma 25-Hydroxyvitamin D, Glycemic Status, and First Stroke in General Hypertensive Adults: Results from the China Stroke Primary Prevention Trial (CSPPT).

BACKGROUND: Associations between vitamin D and stroke remain inconsistent. One major risk factor for stroke is high blood glucose, but the role it plays in this association is not well studied. OBJECTIVES: We aimed to evaluate the individual association between plasma 25-hydroxyvitamin D [25(OH)D] and risk of first stroke stratified by fasting blood glucose (FBG), and the joint associations between plasma 25(OH)D, glycemic status, and first stroke in hypertensive adults. METHODS: This study was a nested, case-control design utilizing data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 591 first stroke cases (of which 475 were ischemic stroke, 114 were hemorrhagic stroke, and 2 were uncertain type) and 591 matched controls. The age range of the study population was 45-75 y. The normal FBG (NFG) group had FBG <5.6 mmol/L,  and the impaired FBG (IFG) group had FBG ≥5.6 mmol/L and <7.0 mmol/L. Diabetes was defined as participants with FBG ≥7 mmol/L or who were receiving treatment with hypoglycemic agents. ORs (95% CIs) were calculated using unconditional logistic regression models. RESULTS: Multivariable adjusted models revealed an inverse association between quartiles of 25(OH)D and risk of first stroke among participants with NFG, but the opposite trend was observed for those with IFG or diabetes. The largest ORs (>2) were observed among patients with diabetes, compared with the reference group of NFG and high 25(OH)D. Those with NFG and low 25(OH)D (OR = 1.73, 95% CI: 1.22 to 2.44) or those with IFG and high 25(OH)D (OR = 1.74, 95% CI: 1.14 to 2.67) both had a higher risk of total stroke. There was a significant interaction between 25(OH)D and a combined group of IFG and diabetes (P = 0.001). Similar results were observed for ischemic stroke. CONCLUSIONS: In a hypertensive population, the relation between plasma 25(OH)D and risk of first stroke was significantly modified by FBG. This trial was registered at https://www.clinicaltrials.gov as NCT00794885.

Association between plasma copper levels and first stroke: a community-based nested case-control study.

BACKGROUND AND AIMS: Uncertainty remains regarding the association between the risk of stroke and plasma copper levels in population with copper mostly in normal range due to limited data. We examined the association between baseline plasma copper and risk of first stroke in Chinese community-dwelling population. METHODS: We conducted a nested case control study from 'H-type Hypertension and Stroke Prevention and Control Project'. A total of 1255 first stroke cases and 1255 controls matched for age, sex and study site were included in the analysis. Conditional logistic regression analyses were performed to evaluate the association between plasma copper and first stroke. RESULTS: The overall mean of copper was 15.90 (2.66) µmol/L. In total, 94.26% participants' copper concentration was in the normal range by Mayo Clinic laboratory reference values. Smoothing curve showed that the associations of plasma copper with first stroke and its subtypes were linear. Each standard deviation (SD) increment of plasma copper was independently and positively associated with risk of first stroke [odds ratio (OR): 1.17, 95% confidence interval (CI): 1.07-1.28]. The multivariable ORs with 95% CIs for total stroke, ischemic stroke and hemorrhagic stroke in the highest versus the lowest quartile of plasma copper were 1.49 (1.16-1.90; P-trend = 0.001), 1.46 (1.12-1.92; P-trend = 0.004) and 2.05 (0.95-4.38; P-trend = 0.050), respectively. CONCLUSIONS: Baseline plasma copper was positively associated with risk of first ischemic stroke in an approximately linear fashion among Chinese community population (80.32% hypertensives), although their copper levels were mostly within the normal range according to current reference values. Our findings warrant additional investigation.

Association between serum 5-methyltetrahydrofolate and homocysteine in Chinese hypertensive participants with different MTHFR C677T polymorphisms: a cross-sectional study.

BACKGROUND AND AIMS: Clarifying the association between 5-methyltetrahydrofolate and homocysteine and the effect pattern of methylene tetrahydrofolate reductase (MTHFR C677T) may contribute to the management of homocysteine and may serve as a significant reference for a randomized controlled trial of 5-methyltetrahydrofolate intervention. This study aimed to reveal the association between these two biochemical indices. METHODS: Study population was drawn from the baseline data of the China Stroke Primary Prevention Trial (CSPPT), including 2328 hypertensive participants. 5-methyltetrahydrofolate and homocysteine were determined by stable-isotope dilution liquid chromatography-tandem mass spectrometry and automatic clinical analyzers, respectively. MTHFR C677T polymorphisms were detected using TaqMan assay. Multiple linear regression was performed to evaluate the association between serum 5-methyltetrahydrofolate and homocysteine. RESULTS: There was a significant inverse association between 5-methyltetrahydrofolate and homocysteine when 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T (per 1-ng/mL increment; All: ß = - 0.50, P <  0.001; CC: ß = - 0.14, P = 0.087; CT: ß = - 0.20, P = 0.011; TT: ß = - 1.19, P <  0.001). Moreover, the decline in trend in genotype TT participants was stronger than in genotype CC participants (P for difference <  0.001) and genotype CT participants (P for difference <  0.001), while there was no significant difference between genotype CC and genotype CT participants (P for difference = 0.757). CONCLUSIONS: Our data showed a non-linear association between serum homocysteine and 5-methyltetrahydrofolate among Chinese hypertensive adults, however, it could be inversely linearly fitted when serum 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T.

Association of visceral adiposity index with new-onset type 2 diabetes and impaired fasting glucose in hypertensive Chinese adults.

PURPOSE: Visceral adiposity index (VAI) is a reliable indicator for the distribution and function of adipose tissue in the body. The relation of VAI with new-onset type 2 diabetes and new-onset impaired fasting glucose (IFG) remains uncertain. We aimed to investigate the prospective relation of VAI with new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive adults. METHODS: A total of 14,838 hypertensive adults free of type 2 diabetes at baseline were included from the China Stroke Primary Prevention Trial. The primary outcome was new-onset type 2 diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary outcome was new-onset IFG, defined as fasting glucose < 6.1 mmol/L at baseline, while fasting glucose ≥ 6.1 mmol/L and < 7.0 mmol/L at the exit visit. RESULTS: Over a median of 4.5 years' follow-up, 1612 (10.9%) participants developed type 2 diabetes. When VAI was categorized into quartiles, compared with participants in quartile 1-3 (< 2.80), significantly higher risk of new-onset type 2 diabetes (OR 1.30; 95% CI 1.08-1.56) and new-onset IFG (OR 1.28; 95% CI 1.08-1.52) was found in those in quartile 4 (≥ 2.80). Moreover, the positive associations were consistent in participants with or without single abnormal VAI components, including general obesity, abdominal obesity, elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C) levels; or with different numbers of abnormal VAI components (all P interactions > 0.05). CONCLUSION: Our study suggested a positive relation of VAI with the risk of new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive patients, independent of its components. LEVEL OF EVIDENCE: Level III, a well-designed cohort.

Comparing the measurement properties of the EQ-5D-5L and the EQ-5D-3L in hypertensive patients living in rural China.

PURPOSE: The purpose of this study was to compare the measurement properties of two versions of EQ-5D (i.e.EQ-5D-3L and EQ-5D-5L) in hypertensive patients in rural China. METHODS: A cross-sectional survey was carried out in hypertensive patients in rural China. We compared the ceiling effects, redistribution properties, informativity, known-groups validity, and relative efficiency of the 3L and 5L and examined their agreement. RESULTS: A total of 11,412 patients were enrolled in our study. The mean EQ-5D index score was 0.84 (SD 0.21) according to the 5L and 0.86 (SD 0.17) according to the 3L. A good agreement was observed between the 3L and 5L. The overall ceiling effect decreased from 46.4% (3L) to 29.4% (5L). The Shannon index, H' improved in all dimensions when used 5L. When used 3L, the median responses of all groups were consistent with 5L across the three dimensions of 'mobility', 'self-care', 'usual activities', while the median responses were inconsistent for the 'pain/discomfort' and 'anxiety/depression' dimensions. The 3L performed better in eight comorbidities in terms of F-statistics and six comorbidities in terms of the area under the receiver operating characteristic curves (AUROCs). The 5L performed better both in terms of the F-statistics and AUROCs in age, education level, anti-hypertensive medication use. CONCLUSION: Taking all comparisons into account, we recommend the EQ-5D-5L for use in patients with hypertension in rural China.

Cigarette smoking and all-cause mortality in rural Chinese male adults: 15-year follow-up of the Anqing cohort study.

BACKGROUND: According to the Global Burden of Disease Study 2017, smoking is one of the leading four risk factors contributing to deaths in China. We aimed to evaluate the associations of smoking with all-cause mortality in a Chinese rural population. METHODS: Male participants over age 45 (n = 5367) from a large familial aggregation study in rural China, were included in the current analyses. A total of 528 former smokers and 3849 current smokers accounted for 10 and 71.7% of the cohort, respectively. Generalized Estimating Equations were used to evaluate the association between baseline smoking status and mortality, adjusting for pertinent covariates. RESULTS: There were 579 recorded deaths during the 15-year follow-up. Current smokers (odds ratio [OR],1.60; 95% CI,1.23-2.08) had higher all-cause mortality risks than nonsmokers. Relative to nonsmokers, current smokers of more than 40 pack-years ([OR],1.85; 95% CI,1.33-2.56) had a higher all-cause mortality risk. Compared to nonsmokers, current smokers who started smoking before age 20 ([OR],1.91; 95% CI,1.43-2.54) had a higher all-cause mortality risk, and former smokers in the lower pack-year group who quit after age 41 (median) ([OR],3.19; 95% CI,1.83-5.56) also had a higher risk of death after adjustment. Furthermore, former smokers who were also former drinkers had the highest significant risk of mortality than never smokers or drinkers. (P for interaction = 0.034). CONCLUSIONS: This study provides evidence that current smokers and former smokers have a higher mortality risk than nonsmokers and would benefit from cessation at a younger age.

Egg consumption associated with all-cause mortality in rural China: a 14-year follow-up study.

BACKGROUND: Dietary recommendations regarding egg intake remain controversial topic for public health. We hypothesized that there was a positive association between egg consumption and all-cause mortality. METHODS: To test this hypothesis, we enrolled 9885 adults from a community-based cohort in Anhui Province, China during 2003-05. Egg consumption was assessed by food questionnaire. Stratified analyses were performed for age, sex, body mass index (BMI), blood pressure, smoking, drinking and laboratory tests. RESULTS: After an average follow-up of 14.1 years, 9444 participants were included for analysis. A total of 814 deaths were recorded. Participants' BMI and lipid profile had no significantly difference between three egg consumption groups. BMI was 21.6±2.7 of the whole population, especially BMI>24 was only 17.3%. A bivariate association of egg consumption >6/week with increased all-cause mortality was observed compared with ≤6/week (RR: 1.35, 95% CI: 1.05, 1.73, P = 0.018). A significant interaction was observed for BMI ≥ 21.2 kg/m2 vs. BMI<21.2 kg/m2 (P for interaction: 0.001). No other significant interactions were found. CONCLUSIONS: In this study, consuming >6 eggs/week increased risk of all-cause mortality, even among lean participants, especially who with BMI ≥ 21.2 kg/m2. Eggs are an easily accessible and constitute an affordable food source in underdeveloped regions. Consuming <6 eggs/week may be the most suitable intake mode.

Plasma 25-Hydroxyvitamin D3 Concentrations and Risk of New-Onset Proteinuria in Patients With Hypertension.

OBJECTIVE: We aimed to evaluate the relationship of plasma 25-hydroxyvitamin D3 (25[OH]D3) with the risk of new-onset proteinuria and examine the possible effect modifiers in patients with hypertension and without chronic kidney disease at baseline. METHODS: This is a post hoc analysis of the renal substudy of the China Stroke Primary Prevention Trial. A total of 1655 patients with hypertension, who had plasma 25(OH)D3 measurements, as well as without proteinuria and with an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 at baseline, were included in the present study. The main outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. RESULTS: The mean (standard deviation) 25(OH)D3 level at baseline was 18.6 (7.5) ng/mL. The median follow-up duration was 4.4 years. Overall, there was a significant inverse association between plasma 25(OH)D3 and the risk of new-onset proteinuria (per standard deviation increment; [odds ratio] OR: 0.70; 95% confidence interval [CI]: 0.50, 0.97). Accordingly, when 25(OH)D3 was assessed as quartiles, a significantly lower risk of new-onset proteinuria was found in participants in quartiles 3-4 (≥17.8 ng/mL; OR: 0.45; 95% CI: 0.23, 0.87), compared with those in quartile 1 (<13.1 ng/mL). Furthermore, a stronger inverse relationship of plasma 25(OH)D3 and new-onset proteinuria was observed in nondiabetic participants (per standard deviation increment; OR: 0.57; 95% CI: 0.39, 0.83; vs. diabetics: OR: 1.48; 95% CI: 0.67, 3.28; P for interaction = 0.028). CONCLUSION: There was a significant inverse association between plasma 25(OH)D3 and the risk of proteinuria in patients with hypertension, especially in those without diabetes.

Carotid Intima-Media Thickness and the Risk of First Stroke in Patients With Hypertension.

Background and Purpose- This study aimed to investigate the association between mean carotid intima-media thickness (cIMT) and the risk of first stroke and examine any possible effect modifiers in patients with hypertension. Methods- A total of 11 547 hypertensive participants without history of stroke from the CSPPT (China Stroke Primary Prevention Trial) were included in this analysis. The primary outcome was first stroke. Results- Over a median follow-up of 4.4 years, 726 first strokes were identified, of which 631 were ischemic, and 90 were hemorrhagic. A per SD increase in mean cIMT was positively associated with the risk of first stroke (hazard ratio [HR], 1.11 [95% CI, 1.03-1.20]), and first ischemic stroke (HR, 1.10 [95% CI, 1.01-1.20]). Moreover, when cIMT was categorized in quartiles, the higher risks of first stroke (HR, 1.31 [95% CI, 1.06-1.61]) and first hemorrhagic stroke (HR, 2.25 [95% CI, 1.11-4.58]) were found in participants in quartile 2 to 4 (≥0.66 mm), compared with those in quartile 1 (<0.66 mm). More importantly, the cIMT-first stroke association was significantly stronger in participants with higher mean arterial pressure (≥109.3 [quintile 5] versus <109.3 mm Hg, P-interaction=0.024) or diastolic blood pressure levels (≥90.7 [quintile 5] versus <90.7 mm Hg, P-interaction=0.009). Conclusions- There was a significant positive association between baseline cIMT and the risk of first stroke in patients with hypertension. This association was even stronger among those with higher mean arterial pressure or diastolic blood pressure levels.