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The functional genetic polymorphisms present in the promoters of stromelysin-1 ( MMP3) and gelatinase B ( MMP9) have been shown to be associated with angiographically measured atherosclerosis; however, haplotype analysis of the genetic polymorphisms occurring in the promoters and coding regions of MMP3 and MMP9 has been infrequently performed in the past. The aim of this study was to analyze the occurrence of the -1612 5A/6A, -376C/G, and Glu45Lys polymorphisms of MMP3 and the -1562C/T and R279Q polymorphisms of MMP9 and their relation to the risk of coronary heart disease (CHD; stenosis ≥50% of the diameter in at least one major coronary artery) in a Chinese Han population. The present study involved 1373 patients with CHD and 695 healthy controls. The Glu45Lys polymorphism of MMP3 was significantly associated with an increased risk of CHD. Compared with the 45Glu homozygotes, 45Lys allele carriers had a significantly elevated risk of CHD (adjusted OR = 1.50; 95%CI 1.11–2.03; p= 0.008). Moreover, haplotype analysis identified both the 6A-C-Lys (-1612 6A, -376C, 45Lys) haplotype and the 6A-G-Lys (-1612 6A,-376G, 45Lys) haplotype of MMP3 as associated with an increased risk of CHD. Our study suggests that common genetic variations in the MMP3 gene may affect the risk of CHD in the Chinese population. [ABSTRACT FROM AUTHOR]

The human plasma kallikrein gene (KLKB1) encodes plasma kallikrein, a serine protease that catalyzes the release of kinins and other vasoactive peptides and may be involved in the pathogenesis of hypertension. In this study, we performed a haplotype-based study to assess the effect of common genetic variation in the KLKB1 gene on the risk of essential hypertension. Eight common single nucleotide polymorphisms (SNPs) were selected from the HapMap database and used to determine the pattern of linkage disequilibrium (LD) and haplotype structure within the KLKB1 gene. Four tag SNPs were then identified with over 85% power to predict both common haplotypes and remaining common SNPs, and genotyped in 1,317 cases with essential hypertension and 1,269 healthy controls. Single SNP analyses indicated that SNPs rs2304595 and rs4253325 were significantly associated with hypertension, adjusted for covariates. Compared with the most common Hap2 CAGC, Hap1 AGAC and Hap3 CGAC, which carry the susceptible rs2304595 G allele and rs4253325 A allele, were found to significantly increase the risk of essential hypertension with adjusted odds ratios equal to 1.37 and 1.17, respectively ( P < 0.0001 and 0.028). A strongly significant interaction with gene-drinking was also observed. Among drinkers, the adjusted OR for Hap1 relative to Hap2 was increased to 2.50 (95% CI, 2.40 to 2.61; P < 0.0001). This was the first study to perform association analysis of the KLKB1 gene with essential hypertension. Our findings suggested that common genetic variation in the KLKB1 gene might contribute to the risk of hypertension in the northern Han Chinese population. [ABSTRACT FROM AUTHOR]

Genetic Predisposition, Sedentary Behavior, and Incident Coronary Artery Disease: A Prospective Chinese Cohort Study. Med. Sci. Sports Exerc., Vol. 56, No. 1, pp. 103-109, 2024. Purpose: Whether the association of sedentary behaviors with coronary artery disease (CAD) can be influenced by genetic susceptibility remains unclear. We aimed to investigate the joint and interplay effects between genetic risk and sedentary time (ST) and to further explore the extent to which the risk for CAD can be counteracted by reducing ST in different genetic groups. Methods: This prospective cohort study included 39,164 Chinese adults without CAD history. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants, and daily ST was assessed by questionnaire. We analyzed the modification effect of genetic risk on the association of ST with CAD using the Cox proportional hazards models. Results: During a median follow-up of 11.60 yr, 1156 CAD events were documented. Higher ST and PRS were separately related to elevated CAD risk. Significant additive interaction was also observed (relative excess risk due to interaction: 0.77; 95% confidence interval [CI] = 0.27–1.28). Compared with participants with low genetic risk and low ST (<6 h·d−1 ), those with high genetic risk and high ST (≥10 h·d−1 ) had the highest CAD risk, with the hazard ratio (HR) and 95% CI of 4.22 (2.65–6.71). When stratified by genetic risks, participants with high ST had gradient increment of CAD risks across low, intermediate, and high genetic risk groups, with HR (95% CI) values of 1.21 (0.61–2.40), 1.57 (1.14–2.16), and 2.15 (1.40–3.31), respectively. For the absolute risk reduction, individuals with high genetic risk achieved the greatest benefit from low ST (Ptrend = 0.024). Conclusions: Genetic susceptibility may synergistically interact with ST to increase CAD risk. Reducing ST could attenuate the CAD risk, especially among individuals with high genetic risk. [ABSTRACT FROM AUTHOR]

BACKGROUND: Heart failure (HF) poses a significant global disease burden. The current evidence on the impact of air pollution on HF remains inconsistent. OBJECTIVES: We aimed to conduct a systematic review of the literature and meta-analysis to provide a more comprehensive and multiperspective assessment of the associations between short- and long-term air pollution exposure and HF from epidemiological evidences. METHODS: Three databases were searched up to 31 August 2022 for studies investigating the association between air pollutants (PM2.5, PM10, NO2, SO2, CO, O3) and HF hospitalization, incidence, or mortality. A random effects model was used to derive the risk estimations. Subgroup analysis was conducted by geographical location, age of participants, outcome, study design, covered area, the methods of exposure assessment, and the length of exposure window. Sensitivity analysis and adjustment for publication bias were performed to test the robustness of the results. RESULTS: Of 100 studies covering 20 countries worldwide, 81 were for short-term and 19 were for long-term exposure. Almost all air pollutants were adversely associated with the risk of HF in both short- and long-term exposure studies. For short-term exposures, we found the risk of HF increased by 1.8% [relative risk (RR)=1.018, 95% confidence interval (CI): 1.011, 1.025] and 1.6% (RR=1.016, 95% CI: 1.011, 1.020) per 10-μg/m³ increment of PM2.5 and PM10, respectively. HF was also significantly associated with NO2, SO2, and CO, but not O3. Positive associations were stronger when exposure was considered over the previous 2 d (lag 0–1) rather than on the day of exposure only (lag 0). For long-term exposures, there were significant associations between several air pollutants and HF with RR (95% CI) of 1.748 (1.112, 2.747) per 10-μg/m³ increment in PM2.5, 1.212 (1.010, 1.454) per 10-μg/m³ increment in PM10, and 1.204 (1.069, 1.356) per 10-ppb increment in NO2, respectively. The adverse associations of most pollutants with HF were greater in low- and middle-income countries than in high-income countries. Sensitivity analysis demonstrated the robustness of our results. DISCUSSION: Available evidence highlighted adverse associations between air pollution and HF regardless of short- and long-term exposure. Air pollution is still a prevalent public health issue globally and sustained policies and actions are called for to reduce the burden of HF. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence remains limited about the association of maternal exposure to ambient fine particulate matter (airborne particles with an aerodynamic diameter ≤2.5 µm [PM2.5]) with fetal congenital heart defects (CHDs) in highly polluted regions, and few studies have focused on preconception exposure. METHODS: Using a nationwide surveillance-based case-control design in China, we examined the association between maternal exposure to PM2.5 during periconception (defined as 3 months before conception until 3 months into pregnancy) and risk of CHD in offspring. The study included 1 434 998 births involving 7335 CHDs from 2014 through 2017 on the basis of the National Population-Based Birth Defects Surveillance System, covering 30 provinces, municipalities, or municipal districts in China. We assigned maternal PM2.5 exposure during the periconception period to each participant using satellite-based PM2.5 concentrations at 1-km spatial resolution. Multilevel logistic regression models were used to calculate the multivariable-adjusted odds ratio and 95% CI for CHDs in offspring associated with maternal PM2.5 exposure, and the exposure–response association was investigated using restricted cubic spline analysis. Subgroup or sensitivity analyses were conducted to identify factors that may modify the association. RESULTS: The average maternal exposure to PM2.5 levels across all participants was 56.51 µg/m³ (range, 10.95 to 182.13 µg/m3). For each 10 µg/m³ increase in maternal PM2.5 exposure, the risk of CHDs in offspring was increased by 2% (odds ratio, 1.02 [95% CI, 1.00 to 1.05]), and septal defect was the most influenced subtype (odds ratio, 1.04 [95% CI, 1.01 to 1.08]). The effect of PM2.5 on CHD risk was more pronounced during the preconception period. Mothers <35 years of age, those living in northern China, and those living in low-income areas were more susceptible to PM2.5 exposure than their counterparts (all P<0.05). PM2.5 exposure showed a linear association with total CHDs or specific CHD types. CONCLUSIONS: High maternal PM2.5 exposure, especially during the preconception period, increases risk of certain types of CHD in offspring. These findings are useful for CHD prevention and highlight the public health benefits of improving air quality in China and other highly polluted regions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of the integrated care in Luohu, China on the hypertension management. Methods: Hypertensive patients aged 35-74 years were recruited by the clusterrandomized sampling method from Luohu district which adopted integrated care and another district that remained original routine care during October 2018-January 2020, with 1353 and 583 patients from integrated and routine care communities, respectively. Health information, knowledge, attitude, and practice (KAP) towards cardiovascular diseases, pharmaceutical expenditure on hypertension and its comorbidities, and healthcare-related satisfaction were collected by questionnaires, with the expenditure additionally verified by hospitals billing records database. Continuous and categorical variables were compared by Wilcoxon test and Chi-square test, respectively. The agestandardized hypertension control rate was calculated by direct standardization. Results: The standardized hypertension management rate in the integrated care communities (45.75%) was significantly higher than that in routine care communities (14.07%) (P < 0.0001), while the age-standardized hypertension control rates were similar (integrated care: 50.3%, routine care: 52.65%, P = 0.518). The pharmaceutical expenditure on hypertension and its comorbidities in the integrated care communities was 264.23 ± 357.38/month/person, lower than that in the routine care communities (354.56 ± 430.59/month/person). Patients in the integrated care had higher KAP scores (73.48 ± 11.54), compared with routine care (68.89 ± 15.51) (P < 0.0001). Moreover, the integrated care communities had higher satisfaction rates towards the convenience of dual referral (90.15% vs. 77.99%) and service quality (95.18% vs. 87.81%) than routine care communities (P < 0.0001). Conclusion: The practice of the integrated care in Luohu has substantially improved the hypertension management and the healthcare-related satisfaction while with relatively low pharmaceutical expenditure. The investigation of long-term impact of the integrated care on hypertension control and management is warranted. [ABSTRACT FROM AUTHOR]

A large proportion of the phenotypic variation in blood pressure (BP) appears to be inherited as a polygenic trait. This study examined the association between 12 single nucleotide polymorphisms (SNPs) in the guanine nucleotide binding protein beta polypeptide 3 ( GNB3) and adducin 1 alpha ( ADD1) genes and systolic (SBP), diastolic (DBP), and mean arterial (MAP) BP. A total of 3,142 individuals from 636 families were recruited from rural north China, and 2,746 met the eligibility criteria for analysis. BP measurements were obtained using a random-zero sphygmomanometer. Genetic variants were determined using SNPlex assays on an automated DNA Sequencer. A mixed linear model was used to estimate the association between each SNP and BP level. After Bonferroni correction, marker rs4963516 of the GNB3 gene remained significantly associated with DBP (corrected P values = 0.006, 0.007 and 0.002 for co-dominant, additive, and recessive models, respectively) and MAP (corrected P values = 0.02, 0.049, and 0.005, respectively). Compared to carriers of the major A allele, CC homozygotes had higher mean DBP (75.81 ± 0.62 vs. 73.46 ± 0.25 mmHg, P = 0.0002) and MAP (91.87 ± 0.68 vs. 89.42 ± 0.28 mmHg, P = 0.0004) after adjusting for covariates of age, gender, BMI, study site, and room temperature during BP measurement. In summary, these data support a role for the GNB3 gene in BP regulation in the Chinese population. Future studies aimed at replicating these novel findings are warranted. [ABSTRACT FROM AUTHOR]

The TH (tyrosine hydroxylase) gene encodes the rate-limiting enzyme of catecholamine biosynthesis, and is involved in the pathogenesis of hypertension, but the relationship of its variants with hypertension has not been extensively studied. We designed a case-controlled study consisting of 503 HT (hypertensive) individuals and 490 NT (normotensive) individuals matched by region, age and gender to systematically investigate the association between the TH gene and hypertension. Based on the HapMap and dbSNP (where SNP is single nucleotide polymorphism) data, four SNPs, rs6356 A>G, rs6357 G>A, rs2070762 T>C and rs1800033 A>G in the TH gene were selected for genotyping. Rs1800033 was not polymorphic in our study population. No significant differences were observed for distributions of rs6356 and rs6357 between the HT and NT groups. However, both the genotype and allele frequencies of rs2070762 showed significant differences between cases and controls (P<0.001 and P=0.005 respectively). In haplotype analysis, a total of eight haplotypes were observed in the entire population and the overall frequency distributions differed significantly between the HT and NT groups. Specifically, haplotype A-A-C (rs6356-rs6357-rs2070762) occurred only in the HT group and A-G-C occurred more commonly in HT subjects than in NT subjects (P=0.003 and P=0.013 respectively). Compared with the most common haplotype A-G-T, the adjusted OR (odds ratio) was 1.83 [95% CI (confidence interval), 1.20–2.79; P=0.0049] for haplotype G-G-C and 20 (P<0.0001) for the haplotype A-A-C. Functional analysis showed that the C allele of rs2070762 functioned as an enhancer in the absence of binding by unidentified transcriptional repressor(s). These results provide evidence for an association of the functional intronic rs2070762 with essential hypertension. [ABSTRACT FROM AUTHOR]

Investigations on the chronic health effects of fine particulate matter (PM2.5) exposure in China are limited due to the lack of long-term exposure data. Using satellite-driven models to generate spatiotemporally resolved PM2.5 levels, we aimed to estimate high-resolution, long-term PM2.5 and associated mortality burden in China. The multiangle implementation of atmospheric correction (MAIAC) aerosol optical depth (AOD) at 1-km resolution was employed as a primary predictor to estimate PM2.5 concentrations. Imputation techniques were adopted to fill in the missing AOD retrievals and provide accurate long-term AOD aggregations. Monthly PM2.5 concentrations in China from 2000 to 2016 were estimated using machine-learning approaches and used to analyze spatiotemporal trends of adult mortality attributable to PM2.5 exposure. Mean coverage of AOD increased from 56 to 100% over the 17-y period, with the accuracy of long-term averages enhanced after gap filling. Machine-learning models performed well with a random cross-validation R² of 0.93 at the monthly level. For the time period outside the model training window, prediction R² values were estimated to be 0.67 and 0.80 at the monthly and annual levels. Across the adult population in China, long-term PM2.5 exposures accounted for a total number of 30.8 (95% confidence interval [CI]: 28.6, 33.2) million premature deaths over the 17-y period, with an annual burden ranging from 1.5 (95% CI: 1.3, 1.6) to 2.2 (95% CI: 2.1, 2.4) million. Our satellite-based techniques provide reliable long-term PM2.5 estimates at a high spatial resolution, enhancing the assessment of adverse health effects and disease burden in China. [ABSTRACT FROM AUTHOR]

The article focuses on the risk of stroke by the Global Burden of Disease (GBD) with the life expectancy in Chinese population.

Background: Cardiovascular disease (CVD) constitutes a major public health problem in China and worldwide. We aimed to examine classical risk factors and their magnitudes for CVD in a Chinese cohort with over 20 years follow-up. Methods: A cohort of 5092 male steelworkers recruited from 1974 to 1980 in Beijing of China was followed up for an average of 20.84 years. Cox proportional-hazards regression model were used to evaluate the risk of developing a first CVD event in the study participants who were free of CVD at the baseline. Results: The multivariable-adjusted hazard ratio (HR) associated with every 20 mmHg rise in systolic blood pressure (SBP) was 1.63 in this Chinese male population, which was higher than in Caucasians. Compared to non-smokers, men who smoked not less than one-pack-a-day had a HR of 2.43 (95% confidence interval [CI], 1.75-3.38). The HR (95% CI) for every 20 mg/dl increase in total serum cholesterol (TC) and for every point rise in body mass index (BMI) was 1.13 (1.04-1.23) and 1.06 (1.02-1.09), respectively. Conclusions: Our study documents that hypertension, smoking, overweight and hypercholesterolemia are major conventional risk factors of CVD in Chinese male adults. Continued strengthening programs for prevention and intervention on these risk factors are needed to reduce the incidence of CVD in China. [ABSTRACT FROM AUTHOR]

Heme oxygenase was regarded as a regulator of oxidative stress, which was believed to underlie the etiology of hypertension. To assess the effect of its encoded genes (HMOX1 and HMOX2) on hypertension, we designed a case-control study in 503 cases and 490 controls. The results indicated that the rs9607267 of the HMOX1 gene was significantly associated with essential hypertension (EH) and the Hap3(T-C-G) of the HMOX1 gene was also significantly associated with the risk of EH. No association was observed between the HMOX2 gene and EH. The multifactor-dimensionality reduction analyses results did not show any interaction between the HMOX1 and HMOX2 genes underlying the development of hypertension. [ABSTRACT FROM AUTHOR]

The human PLA2G7 gene encodes lipoprotein-associated phospholipase A2 (Lp-PLA2), an emerging risk factor for cardiovascular diseases. In the present study, seven single nucleotide polymorphisms (SNPs) in the PLA2G7 gene were genotyped in 827 patients with coronary heart disease (CHD), of which 512 were patients with myocardial infarction (MI), and 947 age- and gender-matched controls in a Chinese Han population. Plasma Lp-PLA2 activity was measured in 416 randomly selected controls and 689 randomly selected CHD patients, including 423 MI patients. Lp-PLA2 activity in CHD and MI cases was significantly higher (233.42 ± 57.66 and 234.27 ± 59.51 nmol ml−1 min−1, respectively) than in controls (211.47 ± 58.61 nmol ml−1 min−1). After adjusting for traditional risk factors by logistic regression, the odds ratios for CHD and MI per 1 standard deviation increment of Lp-PLA2 activity were 1.27 (95% CI, 1.07–1.50) and 1.27 (95% CI, 1.05–1.54), respectively. Both single SNP analysis and haplotype analysis showed that the V279F and I198T polymorphisms were significantly associated with the reduced Lp-PLA2 activity, but neither was associated with increased CHD risk. Both univariate and multivariate analyses, adjusting effects of conventional factors, indicated that the rs13210554 T allele increased the risk of MI in this Chinese Han population. In summary, an independent association of increased plasma Lp-PLA2 activity with CHD and MI existed in this Chinese Han Population. Although V279F and I198T mutations significantly decreased the activity of Lp-PLA2, only the promoter rs13210554 polymorphism was associated with MI. Lp-PLA2 activity appears to influence the CHD and MI risk in Chinese Han population. [ABSTRACT FROM AUTHOR]