Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects.
ABSTRACT: OBJECTIVES:The goal of this study was to determine whether aortic pulse wave velocity (aPWV) improves prediction of cardiovascular disease (CVD) events beyond conventional risk factors. BACKGROUND:Several studies have shown that aPWV may be a useful risk factor for predicting CVD, but they have been underpowered to examine whether this is true for different subgroups. METHODS:We undertook a systematic review and obtained individual participant data from 16 studies. Study-specific associations of aPWV with CVD outcomes were determined using Cox proportional hazard models and random effect models to estimate pooled effects. RESULTS:Of 17,635 participants, a total of 1,785 (10%) had a CVD event. The pooled age- and sex-adjusted hazard ratios (HRs) per 1-SD change in loge aPWV were 1.35 (95% confidence interval [CI]: 1.22 to 1.50; p < 0.001) for coronary heart disease, 1.54 (95% CI: 1.34 to 1.78; p < 0.001) for stroke, and 1.45 (95% CI: 1.30 to 1.61; p < 0.001) for CVD. Associations stratified according to sex, diabetes, and hypertension were similar but decreased with age (1.89, 1.77, 1.36, and 1.23 for age ?50, 51 to 60, 61 to 70, and >70 years, respectively; pinteraction <0.001). After adjusting for conventional risk factors, aPWV remained a predictor of coronary heart disease (HR: 1.23 [95% CI: 1.11 to 1.35]; p < 0.001), stroke (HR: 1.28 [95% CI: 1.16 to 1.42]; p < 0.001), and CVD events (HR: 1.30 [95% CI: 1.18 to 1.43]; p < 0.001). Reclassification indices showed that the addition of aPWV improved risk prediction (13% for 10-year CVD risk for intermediate risk) for some subgroups. CONCLUSIONS:Consideration of aPWV improves model fit and reclassifies risk for future CVD events in models that include standard risk factors. aPWV may enable better identification of high-risk populations that might benefit from more aggressive CVD risk factor management.
Project description:Later chronotype (i.e. evening preference) and later timing of sleep have been associated with greater morbidity, including higher rates of metabolic dysfunction and cardiovascular disease (CVD). However, no one has examined whether chronotype is associated with mortality risk to date. Our objective was to test the hypothesis that being an evening type is associated with increased mortality in a large cohort study, the UK Biobank. Our analysis included 433 268 adults aged 38-73 at the time of enrolment and an average 6.5-year follow-up. The primary exposure was chronotype, as assessed through a single self-reported question-defining participants as definite morning types, moderate morning types, moderate evening types or definite evening types. The primary outcomes were all-cause mortality and mortality due to CVD. Prevalent disease was also compared among the chronotype groups. Analyses were adjusted for age, sex, ethnicity, smoking, body mass index, sleep duration, socioeconomic status and comorbidities. Greater eveningness, particularly being a definite evening type, was significantly associated with a higher prevalence of all comorbidities. Comparing definite evening type to definite morning type, the associations were strongest for psychological disorders (OR 1.94, 95% CI 1.86-2.02, p = < 0.001), followed by diabetes (OR 1.30, 95% CI 1.24-1.36, p = < 0.001), neurological disorders (OR 1.25, 95% CI 1.20-1.30, p = < 0.001), gastrointestinal/abdominal disorders (OR 1.23, 95% CI 1.19-1.27, p = < 0.001) and respiratory disorders (OR 1.22, 95% CI 1.18-1.26, p = < 0.001). The total number of deaths was 10 534, out of which 2127 were due to CVD. Greater eveningness, based on chronotype as an ordinal variable, was associated with a small increased risk of all-cause mortality (HR 1.02, 95% CI 1.004-1.05, p = 0.017) and CVD mortality (HR 1.04, 95% CI 1.00-1.09, p = 0.06). Compared to definite morning types, definite evening types had significantly increased risk of all-cause mortality (HR 1.10, 95% CI 1.02-1.18, p = 0.012). This first report of increased mortality in evening types is consistent with previous reports of increased levels of cardiometabolic risk factors in this group. Mortality risk in evening types may be due to behavioural, psychological and physiological risk factors, many of which may be attributable to chronic misalignment between internal physiological timing and externally imposed timing of work and social activities. These findings suggest the need for researching possible interventions aimed at either modifying circadian rhythms in individuals or at allowing evening types greater working hour flexibility.
Project description:Gallstone disease (GD) is one of the most common presentations to surgical units worldwide and shares several risk factors with cardiovascular disease (CVD). CVD remains the most common cause of death worldwide and results in considerable economic burden. Recent observational studies have demonstrated an association between GD and CVD with some studies demonstrating a stronger association with cholecystectomy. We present the findings of a meta-analysis assessing the relationship between GD and CVD. A total of fourteen cohort studies with over 1.2?million participants were included. The pooled hazard ratio (HR, 95% confidence interval [CI]) for association with GD from a random-effects model is 1.23 (95%CI: 1.16-1.30) for fatal and non-fatal CVD events. The association was present in females and males. Three studies report the relationship between cholecystectomy and CVD with a pooled HR of 1.41 (95%CI: 1.21-1.64) which compares to a HR of 1.30 (95%CI: 1.07-1.58) when cholecystectomy is excluded although confounding may influence this result. Our meta-analysis demonstrates a significant relationship between GD and CVD events which is present in both sexes. Further research is needed to assess the influence of cholecystectomy on this association.
Project description:OBJECTIVE:To examine cause-specific mortality beyond cardiovascular diseases (CVDs) in patients with gout compared to the general population. METHODS:We included all residents of Skåne (Sweden) age ?18 years in the year 2002. Using the Skåne Healthcare Register, we identified subjects with a new diagnosis of gout (2003-2013) and matched each person with gout with 10 comparators free of gout, by age and sex. We used information on the underlying cause of death from the Swedish Cause of Death Register (through December 31, 2014) to estimate hazard ratios (HRs, with 95% confidence intervals [95% CIs]) of mortality for specific causes of death in a multi-state Cox model, with adjustment for potential confounders. RESULTS:Among 832,258 persons, 19,497 had a new diagnosis of gout (32% women) and were matched with 194,947 comparators. Subjects with gout had higher prevalence of chronic kidney disease, metabolic disease, and CVD. Gout was associated with 17% increased hazard of all-cause mortality overall (HR 1.17 [95% CI 1.14-1.21]), 23% in women (HR 1.23 [95% CI 1.17-1.30]), and 15% in men (HR 1.15 [95% CI 1.10-1.19]). In terms of cause-specific mortality, the strongest associations were seen in the relationship of gout to the risk of death due to renal disease (HR 1.78 [95% CI 1.34-2.35]), diseases of the digestive system (HR 1.56 [95% 1.34-1.83]), CVD (HR 1.27 [95% CI 1.22-1.33]), infections (HR 1.20 [95% CI 1.06-1.35]), and dementia (HR 0.83 [95% CI 0.72-0.97]). CONCLUSION:Several non-CV causes of mortality are increased in persons with gout, emphasizing the need for improved management of comorbidities.
Project description:Clinical trials had provided evidence for the benefit effect of antihypertensive treatments in preventing future cardiovascular disease (CVD) events; however, the association between hypertension, whether treated/untreated or controlled/uncontrolled and risk of mortality in US population has been poorly understood. A total of 13,947 US adults aged ?18 years enrolled in the Third National Health and Nutrition Examination Survey (1988-1994) were used to conduct this study. Mortality outcome events included all-cause, CVD-specific, heart disease-specific and cerebrovascular disease-specific deaths, which were obtained from linked 2011 National Death Index (NDI) files. During a median follow-up of 19.1 years, there were 3,550 all-cause deaths, including 1,027 CVD deaths. Compared with normotensives, treated but uncontrolled hypertensive patients were at higher risk of all-cause (HR?=?1.62, 95%CI?=?1.35-1.95), CVD-specific (HR?=?2.23, 95%CI?=?1.66-2.99), heart disease-specific (HR?=?2.19, 95%CI?=?1.57-3.05) and cerebrovascular disease-specific (HR?=?3.01, 95%CI?=?1.91-4.73) mortality. Additionally, untreated hypertensive patients had increased risk of all-cause (HR?=?1.40, 95%CI?=?1.21-1.62), CVD-specific (HR?=?1.77, 95%CI?=?1.34-2.35), heart disease-specific (HR?=?1.69, 95%CI?=?1.23-2.32) and cerebrovascular disease-specific death (HR?=?2.53, 95%CI?=?1.52-4.23). No significant differences were identified between normotensives, and treated and controlled hypertensives (all p?>?0.05). Our study findings emphasize the benefit of secondary prevention in hypertensive patients and primary prevention in general population to prevent risk of mortality later in life.
Project description:We evaluated the rate and risk factors associated with falls and recurrent falls in a multi-ethnic Asian population. 10,009 participants aged ?40 years (mean[SD] age?=?58.9[10.4] years) underwent clinical examinations and completed interviewer-administered questionnaires. Participants who self-reported at least one fall or ?2 falls in past 12 months were defined as fallers and recurrent fallers, respectively. Age-standardized rates for falls and recurrent falls were 13.8% (95%CI, 13.1-14.6%) and 4.6% (95%CI, 4.2-5.1%), respectively. Multivariable analyses showed older age (OR?=?1.20; 95%CI, 1.11-1.30), female gender (OR?=?1.79; 95%CI, 1.54-2.07), diabetes (OR?=?1.22; 95%CI, 1.07-1.40), cardiovascular disease (CVD, OR?=?1.37; 95%CI, 1.14-1.65), ?3 systemic comorbidities (OR?=?1.35; 95%CI, 1.09-1.67), lower European Quality of Life-5 Dimensions (EQ-5D) score (OR?=?1.36; 95%CI, 1.29-1.44), alcohol consumption (OR?=?1.41, 95%CI, 1.11-1.78) and presenting visual impairment (VI, OR?=?1.23; 95%CI, 1.02-1.47) were associated with falls. For recurrent falls, female gender (OR?=?2.27; 95%CI, 1.75-2.94), diabetes (OR?=?1.28; 95%CI, 1.03-1.61), CVD (OR?=?2.00; 95%CI, 1.53-2.62), ?3 systemic comorbidities (OR?=?1.69; 95%CI, 1.19-2.39), lower EQ-5D score (OR?=?1.47; 95%CI, 1.35-1.59), living in 1-2 room public flat (OR?=?1.57; 95%CI, 1.05-2.33), monthly income <2000 Singapore Dollar (OR?=?1.62; 95%CI, 1.13-2.31), alcohol consumption (OR?=?1.81, 95%CI, 1.23-2.66) and presenting VI (OR?=?1.34; 95%CI, 1.01-1.79) were significant risk factors. These findings will be useful for the formulation of fall prevention programs.
Project description:OBJECTIVES:To assess the relationship between metabolic syndrome (MetS) and its components and cardiovascular disease (CVD) according to different criteria of MetS, as well as whether the estimated association between MetS and CVD was affected by different definitions of MetS among the Chinese population. DESIGN:Population-based, cross-sectional study. SETTING:Data were from a large-scale national stroke screening survey, China National Stroke Screening and Prevention Project. PARTICIPANTS:A nationally representative sample of 109 551 Chinese adults aged ≥40 years in 2014-2015 were included. PRIMARY OUTCOME MEASURES:CVD conditions (stroke, coronary heart disease (CHD) and atrial fibrillation (AF)) diagnosed by clinicians were self-reported. RESULTS:ORs after adjusting for CHD, stroke, AF and CVD in those with MetS using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criterion were 1.56 (95% CI 1.48 to 1.63), 1.23 (95% CI 1.17 to 1.30), 1.14 (95% CI 1.08 to 1.21) and 1.40 (95% CI 1.35 to 1.45); 1.51 (95% CI 1.44 to 1.58), 1.20 (95% CI 1.14 to 1.26), 1.09 (95% CI 1.04 to 1.15) and 1.34 (95% CI 1.29 to 1.38) with the American Heart Association/National Heart, Lung, and Blood Institute criterion; and 1.41 (95% CI 1.35 to 1.48), 1.24 (95% CI 1.19 to 1.30), 1.12 (95% CI 1.06 to 1.18) and 1.31 (95% CI 1.27 to 1.35) with the International Diabetes Federation criterion, respectively. Elevated blood pressures were all highly related to the prevalence of stroke and AF, and reduced high-density lipoprotein-cholesterol was associated with a higher OR for CHD than other individual components of MetS. CONCLUSIONS:MetS is significantly associated with CVD, and the prevalence of CVD was more evident when MetS was defined according to the NCEP ATP III criterion. Developing effective public health strategies for the prevention, detection and treatment of MetS should be an urgent priority to reduce the burden of CVD in China.
Project description:BACKGROUND AND PURPOSE:Positive surgical margins (PSMs) correlate with adverse outcomes in numerous solid tumours. However, the prognostic value of PSMs in prostate cancer (PCa) patients who underwent radical prostatectomy remains unclear. Herein, we performed a meta-analysis to evaluate the association between PSMs and the prognostic value for biochemical recurrence-free survival (BRFS), cancer-specific survival (CSS), overall survival (OS), cancer-specific mortality (CSM) and overall mortality (OM) in PCa patients. MATERIALS AND METHODS:According to the PRISMA statement, online databases PubMed, EMBASE and Web of Science were searched to identify relevant studies published prior to February 2018. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate the relationship between PSMs and PCa. RESULTS:Ultimately, 32 cohort studies that met the eligibility criteria and involved 141,222 patients (51-65,633 per study) were included in this meta-analysis. The results showed that PSMs were significantly predictive of poorer BRFS (HR?=?1.35, 95% CI 1.28-1.48, p?<?0.001), CSS (HR?=?1.49, 95% CI 1.16-1.90, p?=?0.001) and OS (HR?=?1.11, 95% CI 1.02-1.20, p?=?0.014). In addition, PSMs were significantly associated with higher risk of CSM (HR?=?1.23, 95% CI 1.16-1.30, p?<?0.001) and OM (HR?=?1.09, 95% CI 1.02-1.16, p?=?0.009) in patients with PCa. CONCLUSIONS:Our study suggests that the presence of a histopathologic PSM is associated with the clinical outcomes BRFS, CSS, OS, CSM and OM in patients with PCa, and PSMs could serve as a poor prognostic factor for patients with PCa.
Project description:OBJECTIVE:Evaluate the association between gout and risk of advanced chronic kidney disease (CKD). DESIGN:Retrospective matched cohort study. SETTING:UK Clinical Practice Research Datalink. PARTICIPANTS:The analysis included data for 68 897 patients with gout and 554 964 matched patients without gout. Patients were aged ≥18 years, registered at UK practices, had ≥12 months of clinical data and had data linked with Hospital Episode Statistics. Patients were excluded for history of advanced CKD, juvenile gout, cancer, HIV, tumour lysis syndrome, Lesch-Nyhan syndrome or familial Mediterranean fever. PRIMARY AND SECONDARY OUTCOME MEASURES:Advanced CKD was defined as first occurrence of: (1) dialysis, kidney transplant, diagnosis of end-stage kidney disease (ESKD) or stage 5 CKD (diagnostic codes in Read system or International Classification of Diseases, Tenth Revision); (2) estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m²; (3) doubling of serum creatinine from baseline and (4) death associated with CKD. RESULTS:Advanced CKD incidence was higher for patients with gout (8.54 per 1000 patient-years; 95% CI 8.26 to 8.83) versus without gout (4.08; 95% CI 4.00 to 4.16). Gout was associated with higher advanced CKD risk in both unadjusted analysis (HR, 2.00; 95% CI 1.92 to 2.07) and after adjustment (HR, 1.29; 95% CI 1.23 to 1.35). Association was strongest for ESKD (HR, 2.13; 95% CI 1.73 to 2.61) and was present for eGFR <10 mL/min/1.73 m² (HR, 1.45; 95% CI 1.30 to 1.61) and serum creatinine doubling (HR, 1.13; 95% CI 1.08 to 1.19) but not CKD-associated death (HR, 1.14; 95% CI 0.99 to 1.31). Association of gout with advanced CKD was replicated in propensity-score matched analysis (HR, 1.23; 95% CI 1.17 to 1.29) and analysis limited to patients with incident gout (HR, 1.28; 95% CI 1.22 to 1.35). CONCLUSIONS:Gout is associated with elevated risk of CKD progression. Future studies should investigate whether controlling gout is protective and reduces CKD risk.
Project description:Several studies suggest that 5-alpha reductase inhibitors (5ARIs) may be associated with elevated risk of cardiovascular disease (CVD). We investigated the association of 5ARI exposure and CVD incidence using the National Health Insurance Service-Health Screening Cohort, a nationally representative population-based sample of Koreans. We calculated the 4-year cumulative exposure to 5ARI for 215,003 men without prior 5ARI use. Participants were followed from January 1st, 2008 to December 31st, 2015. A subcohort of newly diagnosed benign prostatic hyperplasia (BPH) patients during 2004-2010 was also analyzed. The primary study outcome was CVD and secondary outcomes were myocardial infarction (MI) or stroke. Hazard ratios (HRs) were estimated using Cox proportional hazards models adjusted for conventional risk factors. In both the main cohort and BPH subcohort, the use of any 5ARI did not increase the risk of cardiovascular disease (HR = 1.06; 95% CI = 0.91-1.23; HR = 0.95; 95% CI = 0.88-1.03; respectively). Furthermore, as an unexpected finding, a dose-analysis among the BPH subcohort showed that the highest tertile of 5ARI exposure reduced the risk of CVD (HR = 0.82; 95% CI = 0.72-0.92; p-trend = 0.001), MI (HR = 0.69; 95% CI = 0.50-0.95), and stroke (HR = 0.84; 95% CI = 0.72-0.98) compared to non-users. Among men and BPH patients, 5ARI did not increase the risk of CVD. Among BPH patients, 5ARI use may reduce the risk CVD.
Project description:BACKGROUND:The myocardial contraction fraction (MCF: stroke volume to myocardial volume) is a volumetric measure of left ventricular myocardial shortening. We examined the relationship of MCF, measured by cardiac magnetic resonance imaging (cMRI), to incident cardiovascular (CV) events within the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS:Participants (n?=?5000, aged 45-84?years) underwent cMRI. PRIMARY OUTCOME:CVD events (myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease: CHD death, and stroke death). SECONDARY OUTCOMES:CHD and heart failure (HF) events. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for outcomes. RESULTS:There were 299 incident CVD, 188 CHD, and 151 HF events over 10.2?years. The lowest MCF quartile was associated with an increased risk for incident CVD [HR 2.42, CI: 1.58-3.72], CHD [HR 2.32, CI: 1.36-3.96] and HF events [HR 1.99, CI: 1.15-3.44]. In a model adjusted for demographics, CV risk factors, antihypertensive and lipid-lowering medication use, each standard deviation decrease in MCF was associated with incident CVD [HR 1.42, CI: 1.23-1.64], CHD [HR 1.40, CI: 1.17-1.67] and HF [HR 1.58, CI: 1.30-1.94]. In a subgroup analysis of participants with preserved ejection fraction and without left ventricular hypertrophy, the lowest MCF quartile and each standard deviation decrease in MCF was also associated with an increased risk for incident CVD in fully-adjusted analyses. CONCLUSIONS:MCF is a novel measure that can be measured using cMRI. In this multi-ethnic cohort, MCF is a measure that can be used to predict incident CVD events.