| Background and Objective:Stroke is the most common cause of death and severe disability in the world. The relationships between serum total cholesterol (TC) level and risk of stroke and its subtypes are not well established in Asia. We used individual data from the cohorts of China Cohort Studies Collaboration (CCSC) and the Incidence and Comprehensive Control of Metabolic Syndrome Study (ICMS) to explore the impact of baseline TC level on the risks of total stroke, ischaemic and haemorrhagic stroke and its implication in the population prevention of stroke in China.Materials and Methods:A total of62,603participants from CCSC were included, of which data on cholesterol levels at baseline and the outcome of stroke at follow-up were all available. For ICMS, of27,020participants aged35to74at baseline,21,556participants have completed the follow-up survey and19,796participants with full information were analyzed in this study. Participants in these two cohorts were divided into four groups according to the baseline TC level, that was TC<5.18mmol/L (200mg/dl),5.18-5.67mmol/L (200-219mg/dl),5.68-6.21mmol/L (220-239mg/dl) and>6.22mmol/L (240mg/dl). The differences of mean levels of baseline risk factors were compared. Cox regression models were used to estimate the hazard ratios (HR) and95%confidence intervals (CI) for the incidence and death of stroke and stroke subtypes. Population attributable risk percentage (PARP) was also calculated.Results:Over the course of573,894.92person-years of follow-up in CCSC, a total of1,068incident strokes were collected, including367ischaemic strokes,361haemorrhagic strokes and340unclassified strokes. For ICMS, after156,306.26person-years of follow-up, a total of400incident strokes were collected, including227ischaemic strokes,148haemorrhagic strokes and25unclassified strokes.The age-adjusted mean level of baseline TC in ICMS participants was0.23mmol/L (8.88mg/dl) higher than that of CCSC participants. The age-standardized person-year incidence of stroke, ischaemic and haemorrhagic stroke were all higher for both men and women in ICMS. In male subgroup analysis, the standardized person-year mortality of stroke, ischaemic stroke and haemorrhagic stroke were all higher in men from ICMS compared with that in men from CCSC. However, the age-standardized person-year mortality of stroke and haemorrhagic stroke were higher in CCSC in women. The age-standardized person-year mortality of ischaemic stroke was basically the same in both CCSC and ICMS in women.In CCSC, the multivariate-adjusted HRs (95%CIs) for total (fatal or nonfatal) ischemic stroke were1.55(1.17,2.06) and1.77(1.27,2.45) in TC5.18-5.68mmol/L (200-219mg/dl) and TC>6.22mmol/L (240mg/dl) groups compared with the lowest baseline TC level group, respectively. Accordingly, compared with the lowest baseline TC level group, the multivariate-adjusted HRs (95%CIs) for fatal ischemic stroke were1.99(1.22,3.24) and2.31(1.31,4.08) in TC5.18-5.68mmol/L (200-219mg/dl) and TC>6.22mmol/L (240mg/dl) groups, respectively. Each1-mmol/L increase in TC was associated with a21%greater risk of total ischemic stroke (P<0.0001). In ICMS cohort, the multivariate-adjusted HRs for stroke, ischaemic and haemorrhagic stroke were not statistically significant in TC5.18-5.68mmol/L (200-219mg/dl),5.69-6.21mmol/L (220-239mg/dl) and TC>6.22mmol/L (240mg/dl) groups compared with the lowest TC group.For the combined data of CCSC and ICMS, the multivariate-adjusted HRs (95%CIs) for total ischemic stroke were1.31(1.04,1.65),1.45(1.10,1.91) and1.61(1.24,2.08) in TC5.18-5.68mmol/L (200-219mg/dl),5.69-6.21mmol/L (220-239mg/dl) and TC>6.22mmol/L (240mg/dl) groups compared with the lowest TC group, separately. The multivariate-adjusted HRs (95%CIs) for fatal ischemic stroke were correspondingly1.80(1.16,2.79) and2.31(1.42,3.75) in TC5.18-5.68(200-219) and TC≥6.22mmol/L (240mg/dl) groups. Each1-mmol/L increase in TC was significantly associated with a5%,20%and24%higher risk of total stroke, total ischemic stroke and fatal ischemic stroke, respectively. PARP for total stroke and total ischemic stroke was3.6%and11.1%, respectively.The results of subgroup analyses showed that each1-mmol/L increase in TC was significantly associated with a20%higher risk of ischemic stroke for men and17%for women,18%for age<60and19%for age>60,14%for SBP<140mmHg and25%for SBP≥140mmHg, and17%for smokers and21%for never smokers. The multivariate adjusted risk of ischemic stroke was significantly increased in TC5.69-6.21(220-239) and≥6.22mmol/L (240mg/dl) for men, age<60, SBP≥140mmHg and smoker subgroups compared with the reference group. The multivariate-adjusted HR (95%CI) for stroke was1.32(1.06,1.65) in TC>6.22mmol/L (240mg/dl) group for SBP>140mmHg subgroup accordingly. In smokers, the multivariate-adjusted HRs (95%CIs) for total stroke and total haemorrhagic stroke were1.33(1.05,1.69) and1.50(1.01,2.22), respectively. Besides, an elevated HR of total stroke and its subtypes were found when considering TC with the increased number of other risk factors.Conclusions:In the three decades, the serum TC level in Chinese populations significantly increased, so as the incidence of stroke, ischaemic and haemorrhagic stroke in China. The baseline TC level was strongly associated with the risks of stroke and ischaemic stroke in our study. For smokers, the risk of total stroke and total haemorrhagic stroke significantly increased in TC>6.22mmol/L (240mg/dl) compared with TC<5.18mmol/L (200mg/dl). Higher TC levels were strongly associated with increased risks of stroke, ischaemic and haemorrhagic stroke.Reducing serum TC level in residents through primary prevention and lifestyle modification will have an important impact on population prevention and control of stroke in China. Background and Objective:Adiponectin is the most abundant circulating protein secreted by adipocytes. Previous studies have examined the associations between polymorphisms of adiponectin gene (ADIPOQ) and cardiovascular disease (CVD), but those studies have been inconclusive. There is also uncertainty about the association between concentrations of circulating adiponectin and coronary heart disease (CHD) risk. The aims of this study were to evaluate the relationship between three single nucleotide polymorphisms (SNPs),+45T>G (rs2241766),+276G>T (rs1501299) and-11377C<G (rs266729) in ADIPOQ and CVD, and summarize the effect of adiponectin on the incident CHD.Materials and Methods:A comprehensive search was conducted to identify all studies on the association of ADIPOQ gene polymorphisms with CVD risk and the association of adiponectin levels with incident risk of CHD. The fixed and random effect pooled measures (i.e. odds ratio (OR) and95%confidence interval (CI)) were calculated in the meta-analysis. Heterogeneity among studies was evaluated using Q test and the I2. Publication bias was estimated using modified Egger's linear regression test.Results:Thirty-seven studies concerning the associations between the three polymorphisms of ADIPOQ gene and CVD risk were enrolled in this meta-analysis, including6,398cases and10,829controls for rs2241766,8,392cases and18,730controls for rs1501299and7,835cases and14,023controls for rs266729. The three SNPs were significantly associated with CVD, yielding pooled ORs of1.22(95%CI:1.07,1.39; P=0.004),0.90(95%CI:0.83,0.97; P=0.007) and1.09(95%CI:1.01,1.17; P=0.032) for rs2241766, rs1501299and rs266729, respectively. Rs2241766and rs1501299were significantly associated with coronary heart disease (CHD), yielding pooled ORs of1.29(95%CI:1.09,1.52; P=0.004) and0.89(95%CI:0.81,0.99; P=0.025), respectively. The pooled OR for rs266729and CHD was1.09(95%CI:0.99,1.19; P=0.090). Rs2241766and rs266729were significantly associated with stroke, yielding pooled ORs (fixed-effects method) of1.28(95%CI:1.12,1.46; P<0.0001) and1.20(95%CI:1.08,1.34; P=0.0001), respectively. The associations between the three SNPs and hypertension were not significant. Significant between-study heterogeneity and evidence of publication bias were observed in the meta-analysis.Twelve prospective studies comprising8nested case-control studies and4cohort studies were included in the meta-analysis. A total of14,960participants were enrolled and4,132incident CHD events were observed. The pooled RR of CHD was0.83(95%CI:0.69,0.98; P=0.031). The inverse association was consistently observed in men and women and in the studies with mean age<65year. No publication bias was found in our study (P=0.911).Conclusions:The present meta-analysis showed that the associations between rs2241766, rs1501299and rs266729in the ADIPOQ and CVD were significant. Higher levels of adiponectin were associated with a low risk of CHD. The protective effect was consistent in men and women and in the middle-aged populations. High quality studies are still needed to confirm the associations.
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