Additive effect between homocysteine and low-density-lipoprotein cholesterol upon incidence of novel carotid plaque formation: data from a Chinese community-based cohort.

OBJECTIVE: Homocysteine (HCY) has been associated with carotid plaque in cross-sectional studies, but the prospective relationship between HCY and incident carotid plaque has not been well established. The purpose of this study was to investigate the association between HCY and incidence of novel carotid plaque in a Chinese community-based population without pre-existing carotid atherosclerosis and to assess the additive effect of HCY and low-density lipoprotein cholesterol (LDL-C) on the incidence of novel plaque. METHODS: At baseline, we measured HCY and other risk factors in subjects aged ≥ 40 years. All participants underwent carotid ultrasound examinations at baseline and after an average of 6.8 years of follow-up. Incidence of plaque was identified if plaque was absent at baseline, but plaque was detected at the end of follow-up. A total of 474 subjects were included in the analysis. RESULTS: The incidence of novel carotid plaque was 24.47%. Multivariate regression analyses showed that HCY was independently associated with a 1.05-fold-higher likelihood for incident novel plaque (adjusted odds ratio [OR] = 1.05, 95% confidence interval [CI]: 1.01-1.09, P = 0.008). Using tertile 1 and tertile 2 for reference, the top HCY tertile (T3) showed a 2.28-fold-higher likelihood for incident plaque (adjusted OR = 2.28, 95%CI: 1.33-3.93, P = 0.002). The combination of HCY T3 and LDL-C ≥ 3.4 mmol/L had the highest risk for novel plaque formation (adjusted OR = 3.63, 95%CI: 1.67-7.85, P = 0.001) compared to those without either condition. In the LDL-C ≥ 3.4 mmol/L subgroup, HCY was significantly associated with incidence of plaque (adjusted OR = 1.16, 95%CI: 1.04-1.28, P = 0.005, P-interaction = 0.023). CONCLUSION: In the Chinese community-based population, HCY was independently associated with the incidence of novel carotid plaque. There were additive effect between HCY and LDL-C on the incidence of plaque, the highest risk was observed in individuals with both high HCY levels and LDL-C ≥ 3.4 mmol/L. Our findings suggest that HCY may be a potential target for preventing the incidence of carotid plaque, particularly in individuals with elevated LDL-C levels.

Exome-Wide Association Study Identifies East Asian-Specific Missense Variant MTHFR C136T Influencing Homocysteine Levels in Chinese Populations RH: ExWAS of tHCY in a Chinese Population.

Plasma total homocysteine (tHCY) is a known risk factor of a wide range of complex diseases. No genome scans for tHCY have been conducted in East Asian populations. Here, we conducted an exome-wide association study (ExWAS) for tHCY in 5,175 individuals of Chinese Han origin, followed by a replication study in 668 Chinese individuals. The ExWAS identified two loci, 1p36.22 (lead single-nucleotide polymorphism (SNP) rs1801133, MTHFR C677T) and 16q24.3 (rs1126464, DPEP1), showing exome-wide significant association with tHCY (p < 5E-7); and both loci have been previously associated with tHCY in non-East Asian populations. Both SNPs were replicated in the replication study (p < 0.05). Conditioning on the genotype of C677T and rs1126464, we identified a novel East Asian-specific missense variant rs138189536 (C136T) of MTHFR (p = 6.53E-10), which was also significant in the replication study (p = 9.8E-3). The C136T and C677T variants affect tHCY in a compound heterozygote manner, where compound heterozygote and homozygote genotype carriers had on average 43.4% increased tHCY than had other genotypes. The frequency of the homozygote C677T genotype showed an inverse-U-shaped geospatial pattern globally with a pronounced frequency in northern China, which coincided with the high prevalence of hyperhomocysteinemia (HHCY) in northern China. A logistic regression model of HHCY status considering sex, age, and the genotypes of the three identified variants reached an area under the receiver operating characteristic curve (AUC) value of 0.74 in an independent validation cohort. These genetic observations provide new insights into the presence of multiple causal mutations at the MTHFR locus, highlight the role of genetics in HHCY epidemiology among different populations, and provide candidate loci for future functional studies.

Effectiveness of chest pain centre accreditation on the management of acute coronary syndrome: a retrospective study using a national database.

BACKGROUND: Large-scale real-world data to evaluate the impact of chest pain centre (CPC) accreditation on acute coronary syndrome (ACS) emergency care in heavy-burden developing countries like China are rare. METHODS: This study is a retrospective study based on data from the Hospital Quality Monitoring System (HQMS) database. This study included emergency patients admitted with ACS to hospitals that uploaded clinical data continuously to the database from 2013 to 2016. Propensity score matching was used to compare hospitals with and without CPC accreditation during this period. A longitudinal self-contrast comparison design with mixed-effects models was used to compare management of ACS before and after accreditation. RESULTS: A total of 798 008 patients with ACS from 746 hospitals were included in the analysis. After matching admission date, hospital levels and types and adjusting for possible covariates, patients with ACS admitted to accredited CPCs had lower in-hospital mortality (OR=0.70, 95% CI 0.53 to 0.93), shorter length of stay (LOS; adjusted multiplicative effect=0.89, 95% CI 0.84 to 0.94) and more percutaneous coronary intervention (PCI) procedures (OR=3.53, 95% CI 2.20 to 5.66) than patients admitted in hospitals without applying for CPC accreditation. Furthermore, when compared with the 'before accreditation' group only in accredited CPCs, the in-hospital mortality and LOS decreased and the usage of PCI were increased in both 'accreditation' (for in-hospital mortality: OR=0.86, 95% CI 0.79 to 0.93; for LOS: 0.94, 95% CI 0.93 to 0.95; for PCI: OR=1.22, 95% CI 1.18 to 1.26) and 'after accreditation' groups (for in-hospital mortality: OR=0.90, 95% CI 0.84 to 0.97; for LOS: 0.89, 95% CI 0.89 to 0.90; for PCI: OR=1.36, 95% CI 1.33 to 1.39). The significant benefits of decreased in-hospital mortality, reduced LOS and increased PCI usage were also observed for patients with acute myocardial infarction. CONCLUSIONS: CPC accreditation is associated with better management and in-hospital clinical outcomes of patients with ACS. CPC establishment and accreditation should be promoted and implemented in countries with high levels of ACS.

Joint Effects of Body Mass Index and Waist Circumference on the Incidence of Hypertension in a Community-Based Chinese Population.

OBJECTIVE: We aimed to investigate the relationships of body mass index (BMI), waist circumference (WC), and obesity defined using a combination of both indexes, with the incidence of hypertension in a Chinese community-based population. METHODS: A total of 1,927 Chinese participants (57.2 ± 8.9 years old) with normal blood pressure at baseline were recruited from the Shijingshan community in Beijing. Incident hypertension was defined as blood pressure ≥140/90 mm Hg, self-reported hypertension, or the use of any antihypertensive medication at the follow-up visit. RESULTS: During 2.3 years of follow-up, 19.1% (n = 97) of the men and 13.6% (n = 158) of the women developed incident hypertension. The adjusted odds ratios (ORs) (95% confidence intervals [CIs]) for obesity (BMI ≥30) were 3.49 (1.59-7.66) and 2.60 (1.48-4.55) for men and women, respectively. A 1-point increase in BMI was associated with 8% (OR = 1.08, 95% CI: 1.00-1.17) and 10% (OR = 1.10, 95% CI: 1.05-1.16) increases in the incidence of hypertension in men and women, respectively. Abdominal obesity (WC ≥90 cm in men and ≥85 cm in women) was positively associated with incident hypertension in both men (adjusted OR = 1.79, 95% CI: 1.10-2.91) and women (adjusted OR = 1.61, 95% CI: 1.09-2.40). A 1-cm increase in WC was associated with 4% (adjusted OR = 1.04, 95% CI: 1.01-1.07) and 4% (adjusted OR = 1.04, 95% CI: 1.02-1.07) increases in the incidence of hypertension in men and women, respectively. The combination of abnormal BMI and WC has the highest risk for hypertension in both men (adjusted OR = 3.10, 95% CI: 1.48-6.50) and women (adjusted OR = 2.51, 95% CI: 1.43-4.40). CONCLUSIONS: This study shows that BMI, WC, and an index that combined the two are independently associated with incident hypertension in a Chinese community-based population.

Associations of plasma homocysteine levels with peripheral systolic blood pressure and noninvasive central systolic blood pressure in a community-based Chinese population.

Previous studies indicated that homocysteine (Hcy) is associated with higher peripheral systolic blood pressure (pSBP). There have been few data on the relationship between Hcy and central SBP (cSBP). A total of 4,364 Chinese subjects from the Shijingshan community in Beijing were included. cSBP and pSBP were measured with an Omron HEM-9000AI device. Subjects were 57.20 ± 8.9 years old, 37.9% were male. The median of Hcy was 11.96 µmol/L. The mean of cSBP and pSBP was 129.94 ± 18.03 mmHg and 133.25 ± 18.58 mmHg. lnHcy was associated with cSBP (adjusted ß = 2.17, SE = 0.80, P = 0.007) and pSBP (adjusted ß = 2.42, SE = 0.75, P = 0.001). With increasing Hcy, there were enhanced correlations of Hcy with pSBP and cSBP (p for trend between quartiles <0.01). Using Q1 for reference, the Q4 was associated with cSBP (adjusted ß = 1.77, SE = 0.89, P = 0.047) and pSBP (adjusted ß = 2.15, SE = 0.84, P = 0.011). The correlations were more significant in non-obese subjects than in obese subjects (cSBP: ß = 4.30 vs 0.46, pSBP: ß = 5.04 vs 1.18, P for interaction <0.001). Our study showed that Hcy was associated with higher cSBP and pSBP, especially in non-obese subjects.

Body mass index is inversely associated with arterial stiffness in Chinese adults with primary hypertension: results from the China Stroke Primary Prevention Trial (CSPPT).

BACKGROUND: This study aimed to elucidate the relationship between body mass index (BMI) and the presence of arterial stiffness in rural-dwelling Chinese adults with primary hypertension. METHODS: Primary hypertension patients (n = 19,375) receiving an average of 4.5 years of antihypertension therapy were selected from the Chinese Stroke Primary Prevention Trial (mean age: 64.7 ± 7.4 years, male: 37.8%). Anthropometric, demographic, hemodynamic, and biochemical data were obtained. Arterial stiffness was assessed using brachial-ankle pulse wave velocity (baPWV). RESULTS: BMI was inversely associated with baPWV after adjusting for gender, age, smoking, alcohol consumption, center, pulse, SBP, DBP, FBG, TC, TG, HDL-C, BUN, Scr, UA, HCY, antidiabetes treatment, lipid-lowing treatment, and antihypertensive treatment (ß (SE): -10.72 (0.69), P < 0.0001). Quintile1 (Q1) was used as a reference; Q2, Q3, Q4, and Q5 groups were all inversely associated with baPWV. The ß increased with increasing BMI, ß (SE) was -20.29 (6.74), -30.66 (7.01), -51.82 (7.27), and -103.1 (7.62), respectively, for Q2 - Q5, P < 0.05. BMI remained inversely correlated with baPWV across differences in gender, center, blood pressure, lipid levels, and the presence or absence of diabetes subgroups. CONCLUSION: Increased BMI is a positive factor against the development of arterial stiffness in Chinese rural-dwelling adults with primary hypertension undergoing antihypertension treatments, after adjusting for confounding factors.

Relationship between plasma homocysteine level and lipid profiles in a community-based Chinese population.

BACKGROUND: Previous studies established a possible link among hyperhomocysteinemia (HHcy), dyslipidemia, and atherosclerosis. However, there was limited epidemic data concerning the relation between HHcy and lipid profiles, especially in community-based Chinese populations. This study aim to investigate the association of plasma homocysteine (Hcy) level with lipid profiles in a Chinese community-based population without lipid-lowering treatment. METHOD: A total of 4660 Chinese subjects from a cohort of the Shijingshan district in Beijing were included in the analysis. Plasma total Hcy, serum lipid files including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) as well as relevant metabolic risk factors were measured. Multivariate regression models adjusting for age, gender, smoking, drinking, physical activity, vitamin B supplement, body mass index, fasting blood glucose level, serum creatinine, systolic and diastolic blood pressure were used to evaluate associations of Hcy and lipid profiles. RESULT: Subjects were 56.75 ± 8.91 years old, and 38.15% were male. Median (IQR) Hcy was 11.98 (10.00-14.93) µmol/L, and 24.4% had HHcy (defined as Hcy ≥ 15 µmol/L). Mean (SD) baseline TC was 5.34 ± 0.98 mmol/L, LDL-C was 3.27 ± 0.81 mmol/L, and HDL-C was 1.43 ± 0.38 mmol/L. Median (IQR) of TG was 1.28 (0.91-1.85) mmol/L. In multivariable linear-regression analyses, lnHcy (ln transformation for Hcy) level was positively associated with lnTG (adjusted ß = 0.075, SE = 0.021, P = 0.001). Using Hcy < 15 µmol/L as a reference, HHcy was independently associated with both lnTG (adjusted ß = 0.056, SE = 0.020, P = 0.004) and lnHDL (adjusted ß = -0.018, SE = 0.009, P = 0.038). In multivariable logistic-regression analyses, HHcy was associated with increasing risk of low HDL-C (HDL-C < 1.04 mmol/L; adjusted odds ratio [OR] =1.406, 95% confidence interval [CI]: 1.143 - 1.728, P = 0.001) and hypertriglyceridemia (TG ≥ 1.7 mmol/L; adjusted OR = 1.293, 95% CI: 1.096-1.524, P = 0.002) after adjusting the confounders. However, there were no significant associations between Hcy and TC or LDL-C. CONCLUSION: The present study showed that HHcy was independently associated with hypertriglyceridemia and low levels of HDL-C, which provides evidence that Hcy levels might affect HDL-C and TG metabolism.

Renal insufficiency is an independent predictor of in-hospital mortality for patients with acute myocardial infarction receiving primary percutaneous coronary intervention.

OBJECTIVE: To investigate the relationship between renal function and clinical outcomes among patients with acute ST-segment elevation myocardial infarction (ASTEMI), who were treated with emergency percutaneous coronary intervention (PCI). METHODS: 420 patients hospitalized in Peking University First Hospital, diagnosed with ASTEMI treated with emergency (PCI) from January 2001 to June 2011 were enrolled in this study. Estimated glomerular filtration rate (eGFR) was used as a measure of renal function. We compared the clinical parameters and outcomes between ASTEMI patients combined renal insufficiency and the patients with normal renal function. RESULTS: There was a significant increase in the concentrations of fibrinogen and D-Dimer (P<0.05) and a much higher morbidity of diabetes mellitus in the group of patients with chronic kidney disease (CKD; eGFR<60 ml/(min·1.73 m(2))) (P<0.01). CKD (eGFR<60 ml/(min·1.73 m(2))) was an independent predictor of in-hospital mortality for patients hospitalized with ASTEMI receiving PCI therapy rapidly (P=0.032, odds ratio (OR) 4.159, 95% confidence interval (CI) 1.127-15.346). CONCLUSIONS: Renal insufficiency is an independent predictor of in-hospital mortality for patients hospitalized with ASTEMI treated with primary PCI.