Associations between brachial-ankle pulse wave velocity and hypertensive retinopathy in treated hypertensive adults: Results from the China Stroke Primary Prevention Trial (CSPPT).

Although the association between persistent hypertension and the compromise of both micro- and macro-circulatory functions is well recognized, a significant gap in quantitative investigations exploring the interplay between microvascular and macrovascular injuries still exists. In this study, the authors looked into the relationship between brachial-ankle pulse wave velocity (baPWV) and hypertensive retinopathy in treated hypertensive adults. The authors conducted a cross-sectional study of treated hypertensive patients with the last follow-up data from the China Stoke Primary Prevention Trial (CSPPT) in 2013. With the use of PWV/ABI instruments, baPWV was automatically measured. The Keith-Wagener-Barker classification was used to determine the diagnosis of hypertensive retinopathy. The odds ratio (OR) and 95% confidence interval (CI) for the connection between baPWV and hypertensive retinopathy were determined using multivariable logistic regression models. The OR curves were created using a multivariable-adjusted restricted cubic spline model to investigate any potential non-linear dose-response relationships between baPWV and hypertensive retinopathy. A total of 8514 (75.5%) of 11,279 participants were diagnosed with hypertensive retinopathy. The prevalence of hypertensive retinopathy increased from the bottom quartile of baPWV to the top quartile: quartile 1: 70.7%, quartile 2: 76.1%, quartile 3: 76.7%, quartile 4: 78.4%. After adjusting for potential confounders, baPWV was positively associated with hypertensive retinopathy (OR = 1.05, 95% CI, 1.03-1.07, p < .001). Compared to those in the lowest baPWV quartile, those in the highest baPWV quartile had an odds ratio for hypertensive retinopathy of 1.61 (OR = 1.61, 95% CI: 1.37-1.89, p < .001). Two-piece-wise logistic regression model demonstrated a nonlinear relationship between baPWV and hypertensive retinopathy with an inflection point of 17.1 m/s above which the effect was saturated .

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).

Systemic immune-inflammation index predicts first stroke and affects the efficacy of folic acid in stroke prevention.

Background: Systemic immune-inflammation index (SII) is a novel biomarker of growing interest in predicting stroke. The aim of this study was to investigate its predictive value and explore its effect modification on folic acid supplement for stroke primary prevention in a Chinese population with hypertension. Methods: A total of 10,013 participants from the China Stroke Primary Prevention Trial with available neutrophil, platelet and lymphocyte count were included, including 5,019 subjects in the enalapril group and 4,994 in the enalapril-folic acid group. SII was calculated as (platelet × neutrophil)/lymphocyte. The primary endpoint was first stroke. Cox proportional hazards models were used to evaluate the association between SII and first stroke. Results: A U-shape association between SII and first stroke risk was observed in enalapril group. Compared with the reference group (Quartile 2: 335.1 to <443.9 × 109 cell/L), the adjusted HRs were 1.68 (95 % CI: 1.06-2.66, P = 0.027) in Quartile 1 (<335.1 × 109 cell/L), 1.43 (95 % CI: 0.90-2.27, P = 0.126) in Quartile 3 (443.9 to <602.6 × 109 cell/L), and 1.61 (95 % CI: 1.03-2.51, P = 0.035) in Quartile 4 (≥602.6 × 109 cell/L). There was no significant association between SII and first stroke in the enalapril-folic acid group, with adjusted HR of 0.92 (95%CI: 0.54-1.56, P = 0.749) in Quartile 1(<334.7 × 109 cell/L), 1.36 (95%CI: 0.84-2.21, P = 0.208) in Quartile 3 (446.2 to <595.2 × 109 cell/L), and 1.41 (95%CI: 0.87-2.27, P = 0.163) in Quartile 4 (≥595.2 × 109 cell/L). A remarkable interaction between baseline SII and folic acid supplement for stroke prevention was observed, with particularly reduced risk by 44 % (HR: 0.56; 95 % CI: 0.34-0.90; P = 0.018) in the lowest SII group (P for interaction = 0.041). Conclusions: Among Chinese adults with hypertension, both low and high SII at baseline predicted increased first stroke risk. And compensatory folic acid particularly reduced first stroke risk in the lowest SII subgroup.

Association of folic acid dosage with circulating unmetabolized folic acid in Chinese adults with H-type hypertension: a multicenter, double-blind, randomized controlled trial.

Background: There is growing concern regarding elevated levels of circulating unmetabolized folic acid (UMFA) due to excessive intake of folic acid (FA). However, no randomized clinical trial has been conducted to examine the FA-UMFA dose-response relationship. Objective: This study aimed to investigate the FA-UMFA dose-response relationship in Chinese adults with hypertension and elevated homocysteine (H-type hypertension), a population with clear clinical indication for FA treatment. Methods: The data for this study were derived from a randomized, double-blind, multicenter clinical trial of 8 FA dosages on efficacy of homocysteine (Hcy) lowering. The parent trial had three 3 stages: screening period (2-10 days), run-in period (0-2 weeks, baseline visit), and double-blind treatment period (8 weeks) with follow-up visits at the end of the 2nd, 4th, 6th, and 8th weeks of treatment. Participants were randomly assigned to 8 treatment groups corresponding to FA dosages of 0, 0.4, 0.6, 0.8, 1.2, 1.6, 2.0 mg to 2.4 mg. Results: This study included 1,567 Chinese adults aged ≥45 years with H-type hypertension. There was a positive but non-linear association between FA supplementation and UMFA levels in the dosage range of 0 mg to 2.4 mg. In the regression analysis, the coefficients for the linear and quadratic terms of FA dosage were both statistically significant (P < 0.001). Notably, the slope for UMFA was greater for FA dosages >0.8 mg (ß = 11.21, 95% CI: 8.97, 13.45) compared to FA dosages ≤0.8 mg (ß = 2.94, 95% CI: 2.59, 3.29). Furthermore, FA dosages higher than 0.8 mg did not confer additional benefits in terms of increasing 5-methyl tetrahydrofolic acid (5-MTHF, active form of folate) or reducing homocysteine (Hcy). Conclusion: In Chinese adults with H-type hypertension, this study showed a positive, non-linear, dosage-response relationship between FA supplementation ranging from 0 to 2.4 mg and circulating UMFA levels. It revealed that 0.8 mg FA is an optimal dosage in terms of balancing efficacy (increasing 5-MTHF and lowering Hcy) while minimizing undesirable elevation of UMFA. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03472508?term=NCT03472508&draw=2&rank=1, identifier NCT03472508.

Combined use of amlodipine and folic acid are significantly more efficacious than amlodipine alone in lowering plasma homocysteine and blood pressure among hypertensive patients with hyperhomocysteinemia and intolerance to ACEI: A multicenter, randomized, double-blind, parallel-controlled clinical trial.

Hyperhomocysteinemia with hypertension can synergistically increase the risk of stroke. The China stroke primary prevention trial showed that combining 0.8 mg folic acid (FA) with angiotensin-converting enzyme inhibitor (ACEI) can effectively lower plasma total homocysteine (tHcy) and blood pressure (BP); and reduce first stroke risk by additional 21% compared to ACEI alone. However, intolerance to ACEI is common in Asians and amlodipine can be alternative. This is a multicenter, randomized, double-blind, parallel-controlled clinical trial (RCT) which evaluated whether amlodipine combined with FA is more efficacious than amlodipine alone in lowering tHcy and BP among Chinese hypertensive with hyperhomocysteinemia and intolerance to ACEI. 351 Eligible patients were randomly assigned by 1:1:1 ratio to receive amlodipine-FA tablet daily (amlodipine 5 mg/FA 0.4 mg, A group); amlodipine 5 mg/FA 0.8 mg tablet daily (B group); amlodipine 5 mg daily (C group, control group). Follow-up was conducted at 2, 4, 6, and 8 weeks. The primary outcome was efficacy of lowering both tHcy and BP at the end of 8-week treatment. Compared with C group, A group had a significantly higher rate of lowering both tHcy and BP (23.3% vs. 6.0%; Odds Ratio [OR], 8.68; 95% CI, 3.04-24.78, P < .001); B group also had a higher rate of lowering both tHcy and BP (20.3% vs. 6.0%; OR: 5.90; 95% CI, 2.11-16.47, P < .001). This RCT showed amlodipine combined with FA compared with amlodipine alone, each had significantly higher efficacy of lowering both tHcy and BP. No difference was found in BP-lowering and occurrence of adverse events between the three groups.

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.

Geographical, Sex, Age, and Seasonal Differences in Serum Manganese Status Among Chinese Adults with Hypertension.

BACKGROUND: Manganese (Mn) is an essential trace metal element required for optimal human health. However, few studies have assessed the Mn status in hypertensive patients, especially in China. Moreover, factors associated with Mn status have not yet been thoroughly explored. Therefore, we aimed to assess the serum Mn status of adults with hypertension in China and its association with demographic factors. METHODS: An observational, cross-sectional study was conducted to assess serum Mn concentrations in 14 provinces of China. A total of 2597 patients with hypertension were randomly identified by sex, age, and district, and serum Mn concentrations were quantified using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: In our study population, the median serum Mn levels were 1.60 (interquartile range (IQR), 0.94-2.85) µg/L for males and 1.51 (IQR, 0.86-2.69) µg/L for females. In adjusted linear regression models, significantly higher serum Mn concentrations were found in summer (compared with spring, ß, 1.06 µg/L, 95% CI: 0.62 to 1.50), and those living in Guangxi (compared with Heilongjiang, ß, 0.81, 95% CI: 0.06 to 1.56), Shanxi (compared with Heilongjiang, ß, 0.75, 95% CI: 0.01 to 1.50), and Liaoning (compared with Heilongjiang, ß, 1.65, 95% CI: 0.91 to 2.38), and significantly lower serum Mn concentrations were found in patients who aged 60-70 years (compared with those aged < 60 years, ß, - 0.40 µg/L, 95% CI: - 0.76 to - 0.05). CONCLUSION: Our findings observed high serum Mn status among Chinese adults with hypertension, and revealed the association between terms of age, region, and season with serum Mn.

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.

Effect of folic acid supplementation on the change of plasma S-adenosylhomocysteine level in Chinese hypertensive patients: a randomized, double-blind, controlled clinical trial.

The relationship between folic acid and S-adenosylhomocysteine (SAH) is controversial. This study aims to explore the effect of different doses of folic acid supplementation on SAH levels in hypertensive patients and the modification of methylene-tetrahydrofolate reductase (MTHFR) C677T gene polymorphism. A randomized, double-blind, controlled clinical trial was conducted. Hypertensive patients aged 45-75 years without a history of stroke and cardiovascular disease were selected, who were randomly assigned to one of 8 dose groups. This trial has been registered with Trial Number: ChiCTR1800016135. In the total population, folic acid supplementation of 0.4-2.0 mg/day had no effect on SAH level (ß = 0.47, 95% CI: -0.86-1.79, p = 0.491), while folic acid supplementation of 2.4 mg/day significantly increased SAH level (ß = 1.93, 95% CI: 0.22-3.64, p = 0.027). Stratified analysis found that MTHFR C677T genotype CC supplemented with 2.4 mg/day folic acid had no effect on SAH level (ß = 0.30, 95% CI: -2.74-3.34, p = 0.847), while CT and TT genotype supplemented with 2.4 mg/day folic acid showed a significant increase in SAH level (CT: ß = 2.98, 95% CI: 0.34-5.62, p = 0.027; TT: ß = 3.00, 95% CI: -0.51-6.51, p = 0.095; CT combined with TT: ß = 2.99, 95% CI: 0.90-5.09, p = 0.005). In conclusion, supplementation of 2.4 mg/day folic acid can lead to increased SAH levels, especially in MTHFR C677T genotype CT and TT.

Joint Association of Low Vitamin K1 and D Status With First Stroke in General Hypertensive Adults: Results From the China Stroke Primary Prevention Trial (CSPPT).

Background: Vitamin K plays a role in preventing vascular calcification and may have a synergetic influence with vitamin D on cardiovascular health. However, whether this relationship applies to stroke, especially in a high-risk population of hypertensive individuals, remains unclear. The present study aims to study the joint association of low vitamin K1 and D status with first stroke in general hypertensive adults. Methods: This study used a nested, case-control design with data from the China Stroke Primary Prevention Trial. The analysis included 604 first total stroke patients and 604 matched controls from a Chinese population with hypertension. Odds ratios (ORs) and 95% confidence intervals were calculated using conditional logistic regression. Results: There was a non-linear negative association between plasma vitamin K1 and the risk of first total stroke or ischemic stroke in the enalapril-only group. Compared to participants in vitamin K1 quartile 1, a significantly lower risk of total stroke (OR = 0.58, 95% CI: 0.36, 0.91, P = 0.020) or ischemic stroke (OR = 0.34, 95% CI: 0.17, 0.63, P < 0.001) was found in participants in vitamin K1 quartile 2-4 in the enalapril-only group. When further divided into four subgroups by 25(OH)D and vitamin K1, a significantly higher risk of total stroke or ischemic stroke was observed in participants with both low vitamin K1 and 25(OH)D compared to those with both high vitamin K1 and 25(OH)D in the enalapril-only group. No increased risk was observed in the groups low in one vitamin only. Conclusion: Low concentrations of both vitamin K1 and 25(OH)D were associated with increased risk of stroke.

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.

The Association Between Plasma Copper Concentration and Prevalence of Diabetes in Chinese Adults With Hypertension.

Objective: The relationship between plasma copper concentration and prevalence of diabetes in adults with hypertension is unclear. We aimed to determine the association between plasma copper concentration and prevalence of diabetes in Chinese adults with hypertension. Methods: A total of 2,579 participants (697 cases and 1,882 controls) was included in this cross-sectional study. Plasma copper concentrations were determined by inductively coupled plasma mass spectrometry. Multivariable logistic regression model was used to determine the association between plasma copper concentration and prevalence of diabetes. Results: According to the logistic regression analyses, the adjusted OR for the prevalence of diabetes in participants with plasma copper concentration ≥109.4 µg/dL was 1.26 (1.00, 1.58) compared with those with plasma copper concentration <109.4 µg/dL (P = 0.048). The association was no longer significant following further adjusting for serum high-density lipoprotein cholesterol (HDL-C) concentration as a potential confounder. Stratified analyses demonstrated that serum HDL-C concentration significantly modified the association between plasma copper concentration and prevalence of diabetes (P-interaction = 0.043). In the strata of serum HDL-C concentration ≥1.2 mmol/L, a 56% increased prevalence of diabetes was observed in participants with plasma copper concentration ≥109.4 µg/dL compared with those with plasma copper concentration <109.4 µg/dL (P = 0.008). No significant relationship between plasma copper concentration and prevalence of diabetes was found in other strata. Conclusion: Our findings suggested that high plasma copper concentration (≥109.4 µg/dL) was associated with increased prevalence of diabetes in Chinese hypertensive adults with serum HDL-C concentration ≥1.2 mmol/L.

Association between serum manganese levels and diabetes in Chinese adults with hypertension.

Manganese (Mn) is an essential trace metal element that is associated with diabetes; however, the results of previous studies are inconsistent. Furthermore, few studies have been conducted in a hypertensive population. The purpose of this study is to explore the relationship between manganese and diabetes in a population with hypertension. A cross-sectional study was conducted, including 2575 hypertensive individuals from 14 provinces in China. Serum manganese concentrations were measured by the inductively coupled plasma mass spectrometry (ICP-MS) method. And logistic regression models were used to analyze the association between serum manganese and the risk of diabetes. The prevalence of diabetes was 27.0% in this hypertensive population. In logistic regression models, the odds ratios (95% confidence interval) for diabetes in tertile subgroups were 1.40 (1.12, 1.76) and 1.32 (1.05, 1.65) for tertiles 1 and tertiles 3, respectively, compared to tertile 2 (reference). Additionally, an interaction between sex and manganese was observed. The odds ratios (95% confidence interval) for diabetes were 1.29 (0.95, 1.75) and 0.96 (0.70, 1.31) for tertiles 1 and tertiles 3 among males, and 1.44 (1.01, 2.04) and 1.81 (1.29, 2.55) for tertiles 1 and tertiles 3 among females, respectively, compared to tertile 2. In conclusion, a U-shaped association between serum manganese and diabetes was observed in a Chinese population with hypertension, and the association was modified by sex.

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.

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.

Effect of age stratification on the association between carotid intima-media thickness and cognitive impairment in Chinese hypertensive patients: new insight from the secondary analysis of the China Stroke Primary Prevention Trial (CSPPT).

The current study aimed to explore the association between carotid intima-media thickness (CIMT) and cognitive function assessed by the Mini-Mental State Examination (MMSE) and to examine possible effect modifiers in hypertensive patients. A total of 14,322 hypertensive participants (mean age 64.2 ± 7.4 years; 40.9% male) from the China Stroke Primary Prevention Trial (CSPPT) were included in the final analysis. CIMT was measured by ultrasound, and data were collected at the last follow-up visit; MMSE was used to evaluate cognitive function. Nonparametric smoothing plots, multivariate linear regression analysis, subgroup analyses and interaction testing were performed to examine the relationship between the CIMI and cognitive function and effect modification. The mean CIMT was 0.74 ± 0.11 mm, and the mean MMSE score was 23.5 ± 4.8. There was a significant interaction (P interaction < 0.05) in both male and female populations stratified by age (<60 vs. ≥60 years), and higher CIMT was significantly associated with decreased MMSE scores only in participants aged ≥60 years (male: ß = -2.29, 95% CI -3.23 to -1.36; female: ß = -1.96, 95% CI -2.97 to -0.95). Males with abnormal HDL-C showed a stronger negative association (ß = -3.16, 95% CI -4.85 to -1.47) than those with normal HDL-C (normal vs. abnormal, P for interaction = 0.004). We observed that increased CIMT was significantly associated with cognitive impairment in the hypertensive population, especially among individuals with an age greater than 60 years and HDL-C deficiency. Overall, upon diagnosis of hypertension, treatment should start at the earliest opportunity to prevent end-organ damage and cognitive decline.

Inverse association between body mass index and all-cause mortality in rural chinese adults: 15-year follow-up of the Anqing cohort study.

OBJECTIVE: To investigate the association between body mass index (BMI) and all-cause mortality in a Chinese rural population. DESIGN: Prospective cohort study. SETTING: This study was conducted from 2003 to 2018 in Anqing, Anhui Province, China. PARTICIPANTS: 17 851 participants aged 25-64 years (49.4% female) attending physical examinations and questionnaire were included in this study. The inclusion criterion was families having a minimum of three participating siblings. The exclusion criteria included participants without family number and BMI data at baseline. OUTCOME MEASURES: The outcome measure was all-cause mortality. Generalized estimating equation (GEE) regression analysis was performed to determine the association between baseline BMI and all-cause mortality. RESULTS: During a mean follow-up period of 14.1 years, 730 deaths (8.0%) occurred among men, and 321 deaths (3.6%) occurred among women. The mean BMI for males was 21.3[Formula: see text] kg/m2, and for female it was 22.1±3.1 kg/m2. Baseline BMI was significantly inversely associated with all-cause mortality risk for per SD increase (OR, 0.79 (95% CI, 0.72 to 0.87) for males; OR, 0.88 (95% CI, 0.76 to 1.01) for females). When BMI was stratified with cut points at 20 and 24 kg/m2, compared with the low BMI group, a significantly lower risk of death was found in the high BMI group (BMI ≥24: OR, 0.57 (95% CI, 0.43 to 0.77) in males; 0.65 (95% CI, 0.46 to 0.93) in females) after adjustment for relevant factors. CONCLUSIONS: In this relatively lean rural Chinese population, the risk of all-cause mortality decreased with increasing BMI. The excess risk of all-cause mortality associated with a high BMI was not seen among this rural population.

Hypertensive Retinopathy and the Risk of Stroke Among Hypertensive Adults in China.

Purpose: This study aimed to investigate the association between hypertensive retinopathy and the risk of first stroke, examine possible effect modifiers in hypertensive patients, and test the appropriateness of the Keith-Wagener-Barker (KWB) classification for predicting stroke risk. Methods: In total, 9793 hypertensive participants (3727 males and 6066 females) without stroke history from the China Stroke Primary Prevention Trial were included in this study. The primary outcome was first stroke. Results: Over a median follow-up of 4.4 years, 592 participants experienced their first stroke (509 ischemic, 77 hemorrhagic, and six unclassifiable strokes). In total, 5590 participants were diagnosed with grade 1 retinopathy (57.08%), 1466 with grade 2 retinopathy (14.97%), 231 with grade 3 retinopathy (2.36%), and three with grade 4 retinopathy (0.03%). Grades 1 and 2 were merged and classified as mild retinopathy, and grades 3 and 4 were merged and classified as severe retinopathy. There was a significant positive association between hypertensive retinopathy and the risk of first stroke and first ischemic stroke, and no effect modifiers were found. The hazard ratios (HRs) for first stroke were as follows: mild versus no retinopathy, 1.26 (95% confidence interval [CI], 1.01-1.58, P = 0.040), and severe versus no retinopathy, 2.40 (95% CI, 1.49-3.84, P < 0.001). The HRs for ischemic stroke were as follows: severe versus no retinopathy, 2.35 (95% CI, 1.41-3.90, P = 0.001), and nonsignificantly increased HRs for mild versus no retinopathy, 1.26 (95% CI, 0.99-1.60, P = 0.057). Conclusions: There was a significant positive association between hypertensive retinopathy and the risk of first stroke in patients with hypertension, indicating that hypertensive retinopathy may be a predictor of the risk of stroke. A simplified two-grade classification system based on the KWB classification is recommended for predicting stroke risk.

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.