Plasma renin and risk of cardiovascular disease and mortality: the Framingham Heart Study.

AIMS: Previous studies relating plasma renin to cardiovascular disease (CVD) and mortality yielded conflicting results. We related plasma renin to incidence of CVD and mortality in 3408 individuals (mean age 59; 53% women) and in a hypertensive subset (n = 1413). METHODS AND RESULTS: On follow-up (mean 7.1 years), 176 participants (122 hypertensives) developed CVD and 215 individuals (127 hypertensives) died. Overall, log-renin was associated with mortality [multivariable-adjusted hazards ratio (HR) per SD increment: in whole sample, 1.14, 95% confidence interval (CI) 1.00-1.30, P = 0.046; hypertensives, 1.16, 95% CI 1.00-1.35, P = 0.046], but relations varied over time (P < 0.02). Log-renin was associated with mortality at 2.5 years of follow-up (HR per SD increment: whole sample at 2.5 years, 1.23, 95% CI 1.04-1.45; hypertensives at 2 years, 1.28, 95% CI 1.06-1.54), but not during longer follow-up (HR per SD increment at 5 years: whole sample, 1.02, 95% CI 0.80-1.29; hypertensives, 0.98, 95% CI 0.74-1.30). The time-dependent relation of renin and mortality risk was maintained upon excluding participants with prevalent CVD. Renin was not associated with CVD incidence (HR per SD increment log-renin: whole sample, 0.99, 95% CI 0.85-1.14; hypertensives, 0.96, 95% CI 0.82-1.12). CONCLUSION: Higher plasma renin was associated with greater short-term mortality but not with CVD incidence in the community.     

Comparison of cardiovascular mortality between MAFLD and NAFLD: A cohort study

Background and aimsA new diagnostic criterion of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. However, only few studies have shown that MAFLD predicts cardiovascular disease (CVD) mortality better than non-alcoholic fatty liver disease (NAFLD). Therefore, a cohort study was conducted to assess this relationship.Methods and resultsHealth examination data from health care centers in South Korea were assessed after excluding participants with missing covariates and cancer history (n = 701,664). Liver ultrasonography reports, laboratory and anthropometric data were extracted. Diagnoses of NAFLD and MAFLD were performed according to standard definitions. Participants were categorized based on the presence of NAFLD and MAFLD. In addition, participants were classified into five categories: no fatty liver disease (no FLD), NAFLD-only, MAFLD-only, both FLDs, and alcoholic FLD (AFLD) and non-MAFLD. Multivariable regression modeling was performed.The median follow-up duration was 8.77 years, and 52.56% of participants were men. After stratifying the cohort into no-MAFLD and MAFLD groups, MAFLD was associated with increased CVD mortality (adjusted HR 1.14, 95% CI 1.02–1.28). When participants were divided into no-NAFLD and NAFLD groups, there was a non-significant trend towards an increase in CVD mortality in NAFLD group (adjusted HR 1.07, 95% CI 0.95–1.21). When participants were divided into five categories, MAFLD-only group showed increased CVD mortality (adjusted HR 1.35, 95% CI 1.07–1.70) while NAFLD-only group showed no significant association with CVD mortality (adjusted HR 0.67, 95% CI 0.38–1.19).ConclusionsIn conclusion, MAFLD is associated with increased CVD mortality in a relatively young Korean population.     

Serum cystatin C and increased coronary heart disease prevalence in US adults without chronic kidney disease

Previous studies indicated that serum cystatin C, a marker of renal function, was associated with cardiovascular disease (CVD). However, few data about this association are available for persons without chronic kidney disease or albuminuria. Data from 4,991 subjects in the Third National Health and Nutrition Examination Survey with an estimated glomerular filtration rate > or =60 ml/min/1.73 m2 without micro- or macroalbuminuria were analyzed. Subjects were categorized into quartiles of serum cystatin C and compared for prevalence of CVD. CVD was defined as a history of myocardial infarction, angina, or stroke. After age standardization, prevalences of CVD from the lowest to highest quartile of serum cystatin C were 6.0%, 8.8%, 11.8%, and 16.7% (p-trend = 0.006). Also, age-standardized prevalences of myocardial infarction across quartiles of serum cystatin C were 1.9%, 4.4%, 6.6%, and 8.6%; age-standardized prevalences of angina were 2.4%, 4.4%, 4.2%, and 7.1%; and age-standardized prevalences of stroke were 2.5%, 1.6%, 3.5%, and 4.4% (each p-trend <0.05). Each 1-SD higher serum cystatin C level was associated with a multivariate prevalence ratio of CVD of 1.55 (95% confidence interval [CI] 1.13 to 2.13), and multivariate-adjusted prevalence ratios were 1.44 (95% CI 1.01 to 2.07), 1.64 (95% CI 1.02 to 2.64), and 1.65 (95% CI 1.06 to 2.56) for myocardial infarction, angina, and stroke, respectively. In conclusion, a graded association exists between higher serum cystatin C and increased CVD prevalence in patients without established chronic kidney disease.     

Combined effects of high sensitivity C-reactive protein and triglyceride–glucose index on risk of cardiovascular disease among middle-aged and older Chinese: Evidence from the China Health and Retirement Longitudinal Study

Background and aimsHigh sensitivity C-reactive protein (hsCRP) and triglyceride glucose (TyG) index were proved to be independent risk factors of cardiovascular disease (CVD). However, individual hsCRP or TyG index might not provide sufficient predictive value on CVD risk. The current study aimed to evaluate the cumulative effect of hsCRP and TyG index on CVD risk prospectively.Methods and resultsA total of 9626 participants were enrolled in the analysis. The TyG index was calculated as ln(triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The primary outcome was new-onset CVD events (cardiac events or stroke), and the secondary outcomes were new-onset cardiac events and stroke, separately. Participants were divided into 4 groups through the median of hsCRP and TyG index. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportion hazard models. From 2013 to 2018, 1730 participants experienced CVD (570 stroke and 1306 cardiac events). Linear associations were found between hsCRP, TyG index, hsCRP/TyG ratio and CVD (all p < 0.05). Compared to participants with low hsCRP/low TyG index, multivariable adjusted HRs (95% CIs) for those with high hsCRP/high TyG index were 1.17 (1.03–1.37) for CVD. No interaction of hsCRP and TyG index was found on CVD (p_-interaction ≥0.05). Furthermore, adding hsCRP and TyG index simultaneously to conventional risk model improved risk reclassification for CVD, stroke and cardiac events (all p < 0.05).ConclusionThe present study suggested combination of hsCRP and TyG index might better improved the ability for risk stratification of CVD among middle-aged and older Chinese.     

Liver fibrosis marker is an independent predictor of cardiovascular morbidity and mortality in the general population

BackgroundA growing body of evidence suggests that Non-alcoholic fatty liver disease (NAFLD) and liver fibrosis are associated with cardiovascular disease (CVD). However, the independent role of liver fibrosis markers in the prediction of CVD in the general population is seldom tested.AimsTo assess whether a marker of liver fibrosis predicts the first occurrence of a CVD event in a large sample of community-based general population.MethodsHistorical cohort using data from a large health provider that operates a centralized computerized medical record. The level of liver fibrosis was measured by the fibrosis-4 (FIB-4) score, and the association with CVD was adjusted for the European Systematic Coronary Risk Evaluation calculator (SCORE).ResultsThe study included 8,511 individuals, 3,292 with inconclusive fibrosis and 195 with advanced fibrosis (FIB-4 ≥ 2.67). People with advanced fibrosis had higher risk for CVD, after adjustment for sociodemographic characteristics, the SCORE, use of statins and aspirin (HR [95%CI], 1.63 [1.29–2.06]). The association persisted in both women and men. Using age-specific cut-offs, there was a dose-response association between inconclusive and advanced fibrosis and CVD (HR [95%CI], 1.15 [1.01–1.31]) and HR [95%CI], 1.60 [1.27–2.01], respectively, P for trend<0.001).ConclusionsA simple fibrosis score is independently associated with CVD, suggesting that fibrosis markers should be considered in primary-care risk assessment.     

Dietary patterns and cardiovascular disease in Australian adults: Findings from the 2011-12 Australian Health Survey

Background and aimsGreat discrepancies exist in results from studies examining the association between dietary patterns and cardiovascular disease (CVD) in different populations. The aim of this study is to examine the relationship between the Australian Dietary Guidelines (ADG) 2013, Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND), Paleolithic and Okinawan dietary patterns and CVD respectively.Methods and resultsIn this cross-sectional secondary analysis of the 2011-12 Australian Health Survey, adults who self-reported physician-diagnosed CVD, completed two multiple-pass 24 h recalls and had no missing data on all confounders were analysed (weighted n = 5376; 295 CVD cases). Dietary intake was transformed to represent usual intake by the multiple source method. The score of Healthy Eating Index for Australian Adults (HEIFA-2013) was adopted for ADG 2013, while the scores of MIND, Paleolithic and Okinawan dietary patterns were constructed by separating the intake of each predefined food and nutrient into quintiles. The associations between the dietary patterns (as tertiles of scores) and CVD were examined using binary logistic regression adjusted for significant cardiovascular risk factors. Higher adherence to the Okinawan diet pattern was significantly associated with a reduced prevalence of ischemic heart disease (IHD) (OR per unit increase in dietary pattern score: 0.94, 95%CI: 0.90–0.98). Comparing its extreme tertiles, the OR was 0.49 (95%CI: 0.29–0.82; p_trend < 0.01). The associations between HEIFA-2013, MIND and Paleolithic diet patterns and CVD were insignificant.ConclusionThe findings suggested an inverse association between adherence to Okinawan dietary pattern and prevalence of IHD in Australian adults.     

Incremental risk of cardiovascular disease and/or chronic kidney disease for future ASCVD and mortality in patients with type 2 diabetes mellitus: ACCORD trial

BackgroundCardiovascular disease (CVD) and chronic kidney disease (CKD) are complications of type 2 diabetes mellitus (DM). Current cholesterol guidelines recommend the same prevention strategy for patients with DM alone as patients with DM + CKD. However, the incremental risk of these common complications for incident cardiovascular disease and mortality has not been well studied.MethodsWe compared the incremental risk of having DM + CKD, DM + CVD and DM + CVD + CKD in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants for incident CVD as the primary outcome and all-cause mortality.ResultsAfter a mean (SD) follow up of 4.7(1.4) years, 1,046(10%) participants developed CVD. DM +vCKD, DM + CVD, and DM + CKD + CVD had a significantly increased risk of the primary outcome compared to DM alone [adjusted hazard ratio(95%CI): 1.41 (1.06-1.89), p = 0.02; 2.20 (1.92-2.53), p < 0.001); 2.35 (1.81-3.04), p < 0.001), respectively]. All-cause mortality had a graded increased risk compared to the reference group [adjusted hazard ratio(95%CI): 1.39 (1.01-1.90), p = 0.04; 1.29 (1.51-2.12), p < 0.0001; 2.36 (1.75-3.13), p < 0.0001), respectively].ConclusionOur post hoc analysis shows an incremental graded risk for CVD outcomes and all-cause mortality with the development of CKD and/or CVD in individuals with DM.     

The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes: A secondary analysis of the D2d study

AimsLow blood 25(OH)D level is associated with increased cardiovascular disease (CVD) risk. Additionally, individuals with prediabetes are at higher risk for CVD than individuals with normoglycemia. We investigated the effects of vitamin D supplementation on CVD outcomes in the vitamin D and type 2 diabetes (D2d) study, a large trial among adults with prediabetes.Methods2423 participants were randomized to 4000 IU/day of vitamin D₃ or placebo and followed for median 3.0 years for new-onset diabetes. In pre-specified secondary analyses, we examined the effect of vitamin D supplementation on composite Major Adverse Cardiovascular Events (MACE); expanded MACE (MACE + revascularization); atherosclerotic CVD (ASCVD) risk score; and individual CVD risk factors (blood pressure, lipids, high-sensitivity C-reactive protein). Cox models compared hazard ratios (HR) between the two groups on MACE and expanded MACE.ResultsMean age was 60 years, 45 % were women, 13 % had history of CVD. Twenty-one participants assigned to vitamin D and 12 participants assigned to placebo met the MACE outcome (HR 1.81, 95%CI 0.89 to 3.69). There were 27 expanded MACE outcomes in each group (HR 1.02, 95%CI, 0.59 to 1.76). There were no significant differences between vitamin D and placebo in individual CVD risk factors, but change in ASCVD risk score favored the vitamin D group (?0.45 %, 95%CI -0.75 to ?0.15).ConclusionsIn people with prediabetes not selected for vitamin D insufficiency and with intermediate CVD risk, vitamin D supplementation did not decrease MACE but had a small favorable effect on ASCVD risk score.Trial registration: D2d ClinicalTrials.gov number, NCT01942694, prospectively registered September 16, 2013.     

Skin autofluorescence of Advanced Glycation End-products and mortality in older adults: The roles of chronic kidney disease and diabetes

Background and aimAdvanced glycation end products are involved in age-related multisystem decline. They accumulate in body tissues with age, diabetes and chronic kidney disease (CKD), and can be measured non-invasively by the skin autofluorescence (SAF). We studied the relation between SAF and later mortality in old adults.Methods and resultsThe SAF was measured using an AGE-Reader in 451 individuals from the general population aged over 75 years, and all-cause mortality was assessed during an average follow-up of 6.4 years. The association between SAF and mortality was analyzed using a multivariate Cox survival model, adjusted for age and gender. Analyses were further adjusted for diabetes and stratified on the presence of CKD due to its interaction with SAF for the risk of mortality.Participants were 82 years old on average (SD 4.1). Their mean SAF was 2.8 AU (SD 0.6). One hundred and forty-four individuals (31.9%) died during the follow-up. Adjusted for age and gender, SAF was associated with an increased risk of all-cause mortality (HR 1.44, 95%CI: 1.14–1.82 for a one-AU increase of SAF). The association was no longer significant after adjustment for diabetes. However, after stratification for the presence of CKD, higher SAF was associated with an increased risk of all-cause mortality in the participants with CKD at baseline (HR 1.68, 95%CI: 1.11–2.55), whereas there was no association among participants without CKD (HR 0.95, 95%CI: 0.63–1.44).ConclusionSkin autofluorescence is associated with increased all-cause mortality in older adults already suffering from CKD.     

Incident Clinical and Mortality Associations of Myocardial Native T1 in the UK Biobank

BackgroundCardiac magnetic resonance native T1-mapping provides noninvasive, quantitative, and contrast-free myocardial characterization. However, its predictive value in population cohorts has not been studied.ObjectivesThe associations of native T1 with incident events were evaluated in 42,308 UK Biobank participants over 3.17 ± 1.53 years of prospective follow-up.MethodsNative T1-mapping was performed in 1 midventricular short-axis slice using the Shortened Modified Look-Locker Inversion recovery technique (WIP780B) in 1.5-T scanners (Siemens Healthcare). Global myocardial T1 was calculated using an automated tool. Associations of T1 with: 1) prevalent risk factors (eg, diabetes, hypertension, and high cholesterol); 2) prevalent and incident diseases (eg, any cardiovascular disease [CVD], any brain disease, valvular heart disease, heart failure, nonischemic cardiomyopathies, cardiac arrhythmias, atrial fibrillation [AF], myocardial infarction, ischemic heart disease [IHD], and stroke); and 3) mortality (eg, all-cause, CVD, and IHD) were examined. Results are reported as odds ratios (ORs) or HRs per SD increment of T1 value with 95% CIs and corrected P values, from logistic and Cox proportional hazards regression models.ResultsHigher myocardial T1 was associated with greater odds of a range of prevalent conditions (eg, any CVD, brain disease, heart failure, nonischemic cardiomyopathies, AF, stroke, and diabetes). The strongest relationships were with heart failure (OR: 1.41 [95% CI: 1.26-1.57]; P = 1.60 × 10^-9) and nonischemic cardiomyopathies (OR: 1.40 [95% CI: 1.16-1.66]; P = 2.42 × 10^-4). Native T1 was positively associated with incident AF (HR: 1.25 [95% CI: 1.10-1.43]; P = 9.19 × 10^-4), incident heart failure (HR: 1.47 [95% CI: 1.31-1.65]; P = 4.79 × 10^-11), all-cause mortality (HR: 1.24 [95% CI: 1.12-1.36]; P = 1.51 × 10^-5), CVD mortality (HR: 1.40 [95% CI: 1.14-1.73]; P = 0.0014), and IHD mortality (HR: 1.36 [95% CI: 1.03-1.80]; P = 0.0310).ConclusionsThis large population study demonstrates the utility of myocardial native T1-mapping for disease discrimination and outcome prediction.     

Serum copper and the risk of cardiovascular disease death in Finnish men

Background and aimsCopper (Cu) is a component of enzymes catalyzing oxidation-reduction reactions. With the persisting burden of cardiovascular disease (CVD), there is evident need to identify biomarkers and potential risk factors for CVD. We therefore examined the association between serum Cu levels and the risk of CVD death in Finnish men and across different body mass index (BMI) categories.Methods and resultsThis Finnish prospective study is based on 1911 men aged 42–60 years who were free of coronary heart disease at baseline. Cu concentrations (mg/l) were determined using atomic absorption spectrometer and categorized into quartiles (<1.0; 1 to <1.1; 1.1 to <1.21; ≥1.21). Participants were categorized into normal weight <25 kg/m², pre-obesity 25–29.9 kg/m², and obesity >30 kg/m². The association between Cu and CVD death was analyzed using multivariable Cox regression models. During a median follow-up of 25.8 years, 358 CVD deaths occurred. The risk of CVD death increased continuously with increasing Cu levels (for non-linearity, p = 0.64). Using the first quartile as reference after adjustment for covariates, the hazard ratios (HR) (95% confidence interval (CI)) for CVD death for Cu concentrations in second, third and fourth quartiles were 1.45(1.05–2.01), 1.69(1.25–2.27), and 1.68(1.23–2.29), respectively. Obese men in the third quartile of serum Cu concentrations had highest risk of CVD death (HR (95%CI) 2.71(1.27–5.78)).ConclusionElevated serum Cu level was associated with increased risk of CVD death across all BMI categories in middle-aged and older Finnish men. Serum Cu may have prognostic implication for CVD mortality risk; however, further studies are needed.     

Análisis de la relación dosis-respuesta de la actividad física recreativa con los eventos cardiovasculares y la mortalidad por todas las causas: el estudio REGICOR

Introduction and objectivesRegular leisure-time physical activity (LTPA) has been consistently recognized as a protective factor for cardiovascular diseases (CVD) and all-cause mortality. However, the pattern of this relationship is still not clear. The aim of this study was to assess the relationship of LTPA with incident CVD and mortality in a Spanish population.MethodsA prospective population-based cohort of 11 158 randomly selected inhabitants from the general population. LTPA was assessed by a validated questionnaire. Mortality and CVD outcomes were registered during the follow-up (median: 7.24 years). The association between LTPA and outcomes of interest (all-cause mortality and cardiovascular disease) was explored using a generalized additive model with penalized smoothing splines and multivariate Cox proportional hazard models.ResultsWe observed a significant nonlinear association between LTPA and all-cause and CVD mortality, and fatal and nonfatal CVD. Moderate-vigorous intensity LTPA, but not light-intensity LTPA, were associated with beneficial effects. The smoothing splines identified a cutoff at 400 MET-min/d. Below this threshold, each increase of 100 MET-min/d in moderate-vigorous LTPA contributed with a 16% risk reduction in all-cause mortality (HR, 0.84; 95%CI, 0.77-0.91), a 27% risk reduction in CVD mortality (HR, 0.73; 95%CI, 0.61-0.87), and a 12% risk reduction in incident CVD (HR, 0.88; 95%CI, 0.79-0.99). No further benefits were observed beyond 400 MET-min/d.ConclusionsOur results support a nonlinear inverse relationship between moderate-vigorous LTPA and CVD and mortality. Benefits of PA are already observed with low levels of activity, with a maximum benefit around 3 to 5 times the current recommendations.Full English text available from:www.revespcardiol.org/en     

Intra-individual variability of total cholesterol is associated with cardiovascular disease mortality: A cohort study

Background and aimsThe relationship between serum total cholesterol (TC) and mortality remains inconsistent. Additionally, intra-individual variability of cholesterol has been of increasing interest as a new indicator for health outcomes. We aimed to examine the association between TC and its variability and risk of mortality.Methods and resultsWe performed a retrospective cohort study with 122,645 individuals aged over 40 years in Ningbo, China. The intra-individual variability was calculated using four metrics including standard deviation, coefficient variation, variation independent of mean and average successive variability. Hazard ratios and 95% confidence intervals were estimated for the associations of baseline and variability in TC with risk of mortality by Cox proportional hazards regression models. During 591,585.3 person-years of follow-up, 4563 deaths (including 1365 from cardiovascular disease, 788 from stroke and 1514 from cancer) occurred. A U-shaped association was observed for baseline TC level and risk of total, cardiovascular and cancer mortality, with lowest mortality at 5.46 mmol/L, 5.04 mmol/L and 5.51 mmol/L, respectively. As compared with subjects with TC variability in the lowest quartile, individuals in the highest quartile had 21% higher risk of all-cause mortality (HR = 1.21, 95% CI: 1.05 to 1.40), and 41% higher risk of CVD mortality (HR = 1.41, 95%CI: 1.10 to 1.81).ConclusionBoth too low and too high baseline TC level were associated with higher risk of total, cardiovascular disease and cancer mortality. Variability of TC could be a risk factor of total and CVD mortality, independent of mean TC level. Future studies are needed to confirm these findings.     

Higher risk of hospitalized infection,cardiovascular disease,and fracture in patients with rheumatoid arthritis determined using the Japanese health insurance database

Abstract

Objective: To evaluate the risk of hospitalized infection (HI), cardiovascular disease (CVD), stroke, and fracture in rheumatoid arthritis (RA) patients compared with non-RA patients using the Japanese health insurance database.

Method: Among individuals aged ≥18 years, RA cases were defined to have one RA diagnostic code and receiving ≥1 disease-modifying antirheumatic drug between 2005 and 2013 (n?=?6,712). Age-, sex-, calendar year of the observation start-, and observation length-matched non-RA cases were selected at 1:5 (n?=?33,560). Hazard ratios (HRs) were calculated using the time-dependent Cox regression analysis.

Results: Median age of the patients was 52.0 years. The incidence rates of HI, CVD, and fracture in the RA group were 2.42/100 person-years (PY), 4.94/1,000 PY, and 10.59/1,000 PY. The crude incidence rate ratios (95% CI) (RA vs. non-RA) for HI, CVD, and fracture were 2.47 (2.20–2.77), 1.89 (1.49–2.41), and 3.35 (2.80–4.02). The adjusted HR (95% CI) (RA vs. non-RA) was significantly elevated (HI, 1.74 [1.52–1.99], CVD, 1.38 [1.04–1.85], and fracture, 1.88 (1.54–2.31)].

Conclusion: The relatively young RA population had significantly higher risks of these complications than the non-RA, indicating importance of prevention of them even at young ages in clinical settings.     

Dabigatran,rivaroxaban, and apixaban are superior to warfarin in Asian patients with non-valvular atrial fibrillation: An updated meta-analysis

BACKGROUNDMost of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation (AF) originated from western countries. AIMTo systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran, rivaroxaban, and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.METHODSMedline, Cochrane, and ClinicalTrial.gov databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. The primary outcome was ischemic stroke. The secondary outcomes were all-cause mortality, major bleeding, intracranial hemorrhage, and gastrointestinal bleeding.RESULTSTwelve studies from East Asia or Southeast Asia and 441450 patients were included. Dabigatran, rivaroxaban, and apixaban were associated with a significant reduction in the incidence of ischemic stroke [hazard ratio (HR) = 0.78, 95% confidence interval (CI): 0.65-0.94; HR = 0.79, 95%CI: 0.74-0.85, HR = 0.70, 95%CI: 0.62-0.78; respectively], all-cause mortality (HR = 0.68, 95%CI: 0.56-0.83; HR = 0.66, 95%CI: 0.52-0.84; HR = 0.66, 95%CI: 0.49-0.90; respectively), and major bleeding (HR = 0.61, 95%CI: 0.54-0.69; HR = 0.70, 95%CI: 0.54-0.90; HR = 0.58, 95%CI: 0.43-0.78; respectively) compared to warfarin.CONCLUSIONDabigatran, rivaroxaban, and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.     

Association of peroxisome proliferator-activated receptor delta and additional gene–smoking interaction on cardiovascular disease

Aims: To investigate the impact of peroxisome proliferator–activator receptor delta (PPARD) gene polymorphism and additional gene–smoking interaction on cardiovascular disease (CVD) risk based on this Chinese population. Methods: A total of 1048 subjects (617 males, 431 females) with a mean age of 52.9 ± 14.1 years old were selected, including 520 CVD patients and 528 normal control subjects. The logistic regression model was used to examine the association between three SNPs and CVD risk, odds ratio (OR), and 95% confident interval (95%CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to investigate the gene–smoking interaction. Results: Genotypes of variants in rs2016520 and rs9794 were associated with decreased CVD risk, and CVD risk was significantly lower in carriers of C allele of the rs2016520 polymorphism than those with the TT genotype (TC+CC versus TT), adjusted OR (95%CI) = 0.71 (0.56–0.86). In addition, we also found that CVD risk was also significantly lower in carriers of the G allele of the rs9794 polymorphism than those with the CC genotype (CG+ GG versus CC), adjusted OR (95%CI) = 0.69 (0.53–0.86). GMDR analysis suggested a potential gene–environment interaction between rs2016520 and smoking. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 62.17%, and never smokers with TC or CC of the rs2016520 genotype have the lowest CVD risk, compared to smokers with TT of rs2016520, OR (95%CI) was 0.42 (0.23–0.66). Conclusions: The minor allele of rs2016520 and rs9794 in PPAR-δ and interaction between rs2016520 and non-smoking were associated with decreased risk of CVD.     

中国及各省份人群不同肥胖指标心血管疾病负担比较

探讨我国不同地区由肥胖引起的心血管疾病负担的差异。方法 基于中国高血压调查,随机选取30036名35岁以上研究对象进行随访。使用来自CHS的数据计算全国和省的不同肥胖指标的加权患病率,采用Cox回归分析计算不同肥胖指标全国及分省的心血管疾病校正风险比（Hazard ratio, HR）并估算人群归因百分比（Population attributable fractions, PAFs）。结果：研究纳入325552名CHS参与人群和22793名队列研究人群（平均4.56年的随访,其中1109名参与者发生了至少一次心血管事件）。在全国层面,与正常体重（BMI＜24 Kg/m2）相比,在调整了年龄、教育水平、吸烟、饮酒等多种危险因素后,所有肥胖指标均与CVD风险增加有统计学差异。其中,超重和肥胖的HR分别为正常体重指数的1.18倍（95% CI 1.03~1.34）和1.53倍（95% CI 1.29~1.81）,超重人群心血管疾病的PAFs为6.20%（95% CI 6.16%~6.24%）,肥胖7.08%（95% CI 6.99%~7.17%）;腹型肥胖的HR为1.44 （95% CI 1.27-1.62）,PAFs为13.30%（95% CI 13.21%~13.37%）;体脂率的HR为1.25（95% CI 1.10~1.41）,PAFs为8.99%（95% CI 8.94%~9.04%）;内脏脂肪指数的HR为1.43（95% CI 1.23~1.65）,PAFs为5.14%（95% CI 5.07%~5.21%）。对于各省而言,肥胖的PAFs分布北部和西部省份最高,南部和沿海省份最低。体重指数肥胖的PAFs天津最高为13.31%,海南最低为2.37%;腹型肥胖的PAFs天津最高20.78%,海南最低5.38%。结论：我国心血管疾病很大比例可归因于肥胖。腰围指标较其他肥胖指标心血管疾病PAFs更高,我国北方和经济社会地位较低的省份心血管疾病PAFs显著偏高。     

Biomarkers of kidney function and prediction of death from cardiovascular and other causes in the elderly: A 9-year follow-up study

BackgroundCystatin C is claimed to be superior to creatinine-based estimates of glomerular filtration rate (eGFRcr). The purpose of the study is to analyze whether cystatin C, creatinine, and/or estimated glomerular filtration rates (eGFR) predicted cardiovascular and/or non-cardiovascular deaths among Finnish elderly.MethodsHazard ratios (HR) of cystatin C, creatinine and eGFRs for cardiovascular and non-cardiovascular deaths.ResultsDuring a 9-year follow-up, 275 died, 192 deaths were a result of cardiovascular disease. In age-adjusted analyses, cystatin C predicted the risk of non-cardiovascular and cardiovascular death in men (HR for 0.1-unit increase 1.12 [95% CI, 1.04–1.19] for non-CVD deaths and 1.18 [1.09–1.28] for CVD deaths) and women (1.14 [1.07–1.21] and 1.14 [1.06–1.22], respectively). CKD-EPIcr-cyc predicted the risk of CVD deaths in men (HR for 5-unit decrease 1.17 [1.09–1.25]) and women (1.09 [1.02–1.17]) and non-CVD deaths in women (1.07 [1.01–1.14]). Also, MDRD (HR for 5-unit decrease 1.16 [1.05–1.27]) and CKD-EPI (HR for 5-unit decrease 1.15 [1.05–1.25]) predicted CVD deaths among men. After additional adjustments, predictive value of cystatin C remained significant. Also, the predictive value of CKD-EPIcr-cys remained significant in non-CVD deaths among women.ConclusionCystatin C was clearly the best predictor for cardiovascular and non-cardiovascular deaths among Finnish elderly. Serum cystatin C is more accurate for clinical decision making than creatinine-based eGFR equations or the combined CKD-EPIcr-cys equation in persons older than 64 years.     

Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study

Background and aimPlasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions.Methods and resultsCase-cohort study from the PREDIMED trial involving participants aged 55–80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20–1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12–1.58) for fumarate and 1.47 (95%CI:1.21–1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32–1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention.ConclusionPlasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk.Clinical trial numberISRCTN35739639     

Cystatin C and incident peripheral arterial disease events in the elderly: results from the Cardiovascular Health Study

BACKGROUND: The association of cystatin C, a novel marker of renal function, with risk for developing complications related to peripheral arterial disease (PAD) has not been examined. METHODS: We evaluated the hypothesis that a high cystatin C concentration is independently associated with future PAD events among 4025 participants in the Cardiovascular Health Study who underwent serum cystatin C measurement at the 1992-1993 visit and who did not have PAD at baseline. The association of cystatin C quintiles with time to first lower-extremity PAD procedure (bypass surgery, angioplasty, or amputation) was evaluated using multivariable proportional hazards models. Secondary analyses were conducted using quintiles of serum creatinine level and estimated glomerular filtration rate (eGFR). RESULTS: The annualized risk of undergoing a procedure for PAD was 0.43% per year among participants in the highest cystatin C quintile (>1.27 mg/L) compared with 0.21% per year or less in all other quintiles. After multivariable adjustment for known risk factors for PAD, elevated cystatin C levels remained associated with the outcome (hazard ratio, 2.5 for highest vs lowest quintile of cystatin C, 95% confidence interval, 1.2-5.1). The highest quintiles of serum creatinine level and eGFR were not associated with future PAD events in either unadjusted or adjusted analyses. CONCLUSION: Elevated concentrations of cystatin C were independently predictive of incident PAD events among community-dwelling elderly patients.