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/m(2) compared with >= 25 kg/m(2), 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/m(2). 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.

BACKGROUND:In China, the MTHFR 677T allele, unlike in most Western populations, is a rare genetic variant linked to various disorders. The contributing nutritional and genetic factors to this genetic risk remain unclear. OBJECTIVE:This study aimed to elucidate the interactions between genetic variations in total homocysteine (tHcy) pathway genes, serum tHcy concentrations, and nutritional factors in a Chinese population with hypertension. METHODS:This study analyzed 1304 Chinese adults with hypertension aged ≥18 y enrolled in the China Precision Nutrition and Health KAP Real World Study (CPNAS). Serum concentrations of vitamin B12 and folate were measured using the magnetic microparticle chemiluminescence method, and tHcy concentrations were measured using Hcy Assay kits. Identification of the MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms was performed via time-of-flight nucleic spectrometry. RESULTS:Our findings revealed significant sex differences in tHcy concentrations, with males exhibiting higher tHcy concentrations than females (13.95 μmol/L vs. 11.15 μmol/L, P < 0.001). Individuals deficient in both vitamin B12 and folate had an increased risk of hyperhomocysteinemia (H-Hcy) (57.4%). In contrast, the prevalence of H-Hcy was lower among those deficient in either vitamin B12 (31.1%) or folate (23.2%) alone. Significant associations were identified between the MTHFR C677T and A1298C polymorphisms and elevated serum tHcy concentrations, particularly in individuals homozygous for the T allele. Conversely, the MTRR A66G genotype did not show a significant correlation with tHcy concentrations. Optimal vitamin B12 concentrations significantly modulated the genotypic effect on tHcy concentrations, with individuals having adequate vitamin B12 and folate exhibiting low tHcy concentrations, even among high-risk genotypes (TT). CONCLUSIONS:Adequate concentrations of folate and vitamin B12 significantly reduce serum tHcy concentrations and mitigate the genotypic impact on tHcy concentrations, highlighting the potential for targeted nutritional interventions to manage cardiovascular risks associated with H-Hcy. This trial was registered at clinicaltrials.gov as ChiCTR2100051983.

Dear Editor, Congenital hypogonadotropic hypogonadism(CHH)is a rare genetic disease characterized by gonadotropin-releasing hormone(GnRH)deficiency or insufficiency and normal hypothalamic-pituitary structures,resulting in defective sexual maturation or/and infertility.1 CHH presents as a variety of nonreproductive phenotypes,such as renal hypoplasia,dental hypoplasia,or oculomotor abnormalities.Most pubertal patients exhibit delayed puberty and the underdevelopment of secondary sexual characteristics.2 GnRH therapy is widely used for the treatment of male CHH patients.2 However,a small proportion of these patients show an atypical response to GnRH treatment,with abnormal hormone levels,a lack of spermatogenic activity,or persistently small testicular volume.Insensitivity to GnRH treatment may be attributed to GnRH receptor gene(GNRHR)mutations that negatively affect the response to GnRH therapy.3 However,this hypothesis has not been fully verified in clinical samples.In this study,we identified compound heterozygous mutations of GNRHR in a Chinese family featuring two CHH patients.Subsequently,we enrolled three male CHH patients who did not carry variants of GNRHR or DSS-AHC critical region on the X chromosome 1,gene 1(DAX1),and performed GnRH stimulation tests to investigate whether GNRHR mutations affect the sensitivity of male CHH patients to GnRH treatment.

Context: In 2015, we reported an increased prevalence of thyroid disease in a county of low habitual selenium (Se) intake in comparison to a neighboring county with higher intake in a cross-sectional survey in Shaanxi Province, China. Objective: To explore longitudinal effects of low Se status, a prospective cohort study was conducted in the same area from 2013 to 2019, and thyroid peroxidase autoantibodies (TPO-Abs) and disease incidence were compared. Methods: A total 1254 individuals from 1500 reinvited participants were successfully enrolled. Venous blood, fingernails, and urine samples were collected and analyzed to evaluate thyroid status, TPO-Abs, serum Se, and urinary iodine. Diagnosis of Hashimoto thyroiditis (HT) was based on elevated thyrotropin, presence of TPO-Abs, and ultrasound characteristics. Se deficiency was categorized using a serum concentration of 80 mu g/L as a threshold, and tested by logistic regression for a relationship to TPO-Abs and HT. Results: Se deficiency was observed in 46.2% of participants from the adequate-Se county (Ziyang) and in 89.7% from the low-Se county (Ningshan). Se concentrations in fingernails differed strongly by residency (Ziyang vs Ningshan; 678.7 vs 364.3 mu g/kg; Z= -9.552; P < .001). Newly diagnosed HT in Ziyang was less frequent than in Ningshan (0.09% vs 0.31%; chi(2) = 4.350; P= .037). The conversion rate to seropositive TPO-Abs was 10.2% in Ningshan vs 5.6% in Ziyang. Excluding iodine as confounding factor, low-Se was confirmed as a risk factor for HT (relative risk [95% CI]; 3.65 [1.03-12.90]; P < .05). Conclusion: The data indicate an increased incidence of TPO-Ab seroconversion with low Se supply and support the hypothesis that Se deficiency contributes to HT as a modifiable risk factor.

AimThe relationship of vitamin B5 and coronary heart disease (CHD) is still uncertain. This case–control study was performed to evaluate the relationship between the plasma vitamin B5 concentration and the risk of CHD.Materials and methodsThe study involved 429 patients with >70% stenosis of the coronary arteries on coronary angiography and 429 matched controls were included for age ± 2 years, gender, and date of coronary angiography examination ± 180 days. Logistic regression analyses were performed to evaluate the association between plasma vitamin B5 and the risk of CHD.ResultsAn L-shaped relationship was found between the plasma vitamin B5 concentration and CHD. Compared with patients with low vitamin B5 (first quartile, <27.6 ng/ml), the odds ratio (OR) and 95% confidence interval (CI) for participants in the third quartile (34.9–44.0 ng/ml) and fourth quartile (≥44.0 ng/ml) were 0.42 (95% CI, 0.26–0.70) and 0.49 (95% CI, 0.29–0.82), respectively. In the threshold effect analysis, the risk of CHD significantly decreased as the vitamin B5 concentration increased (per 10 ng/ml increment: OR, 0.71; 95% CI, 0.57–0.89) in participants with a plasma vitamin B5 concentration of <40.95 ng/ml; however, an increased plasma vitamin B5 concentration was no longer associated with a decreased risk of CHD (per 10 ng/ml increment: OR, 1.00; 95% CI, 0.87–1.14) in participants with a plasma vitamin B5 concentration of ≥40.95 ng/ml. The association between vitamin B5 and CHD was stronger in ever or current smokers than non-smokers (p-interaction = 0.046).ConclusionPlasma vitamin B5 has an L-shaped relationship with CHD, with a threshold around 40.95 ng/ml. This association was modified by smoking.

Background: The association between plasma vitamin E levels and first stroke risk in men and women remains unclear. Objective: We aimed to examine the prospective association between plasma vitamin E and first stroke, and evaluate the effect modifiers for the association, among hypertensive patients. Design: The study sample was drawn from the China Stroke Primary Prevention Trial (CSPPT), which randomized a total of 20,702 hypertensive patients to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. This nested case-control study, including 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site, was conducted after the completion of the CSPPT. Results: The median follow-up duration was 4.5 years. Among men, a significantly higher risk of first stroke (adjusted OR, 1.67; 95%CI: 1.01, 2.77) was found for those with plasma vitamin E ≥7.1 μg/mL (≥quartile 1) compared with those with plasma vitamin E < 7.1 μg/mL. Subgroup analyses further showed that the association between vitamin E (≥7.1 vs. <7.1 μg/mL) and first stroke in men was significantly stronger in non-drinkers (adjusted OR, 2.64; 95%CI: 1.41, 4.96), compared to current drinkers (adjusted OR, 0.84; 95% CI: 0.43, 1.66, P-interaction = 0.008). However, there was no significant association between plasma vitamin E and first stroke in women (P-interaction between sex and plasma vitamin E = 0.048). Conclusions: Among Chinese hypertensive patients, there was a statistically significant positive association between baseline plasma vitamin E and the risk of first stroke in men, but not in women. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00794885, Identifier: NCT00794885.

Background: Copper is an essential micronutrient and plasma copper plays an important role in the development of myocardial infarction and cardiovascular disease (CVD)-specific mortality. However, nationwide data on the plasma copper concentrations and determinants in Chinese adults with hypertension is limited. Aims: We aimed to assess the range of plasma copper concentrations and its associations with demographic, environmental, lifestyle and dietary factors in a nationwide cohort of Chinese adults with hypertension. Methods: A cross-sectional study including 2599 adults (1389 males and 1210 females) with hypertension was conducted from February 2017 to May 2018 in 14 provinces in China. Plasma copper concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). Results: The mean concentration of plasma copper was 95.3 ± 18.9 μg/dL for all participants, and 90.8 ± 18.2 μg/dL in males and 100.4 ± 18.5 μg/dL in females, respectively. In adjusted linear regression models, those living in areas with daily mean temperature (Tm) < 14.5 ℃ were positively associated with plasma copper concentrations compared with those in areas with Tm ≥ 24.7 ℃ (β = 4.55, 95% CI = 2.83, 6.27; P < 0.001). Similar associations were observed in patients who were female, aged ≥ 65 years, currently smoking and currently drinking alcohol. Conclusions: The mean plasma copper concentration of Chinese adults with hypertension was 95.3 ± 18.9 μg/dL. Participants who were female, aged ≥ 65 years, living in areas with Tm < 14.5 ℃, or currently smoking or drinking alcohol were positively associated with plasma copper concentrations, indicating the potential impact of demographic, environmental, lifestyle and dietary factors on plasma copper concentrations.

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 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 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 to 0.21) and diabetes (OR=1.16, 95% CI 1.10 to 1.21). 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 vitamin B12 measurements, we found a positive association between an increase in vitamin B12 and an increase in FBG.Conclusions In this large Chinese population of patients with hypertension 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.