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Background Neighborhood‐level income is inversely associated with cardiovascular events; however, it is uncertain whether this association varies with immigration status. Methods and Results We conducted a population‐based cohort study of 5.2 million (53% women, 19% immigrants) urban‐dwelling people aged ≥40 years without a prior history of cardiovascular disease in Ontario, Canada. Neighborhood‐level income was measured in quintiles from quintile 1 (lowest) to quintile 5 (highest), and immigrants were defined as those born outside of Canada who moved to Canada after 1985. We estimated the association between neighborhood‐level income and the rate of incident cardiovascular events (hospitalization for stroke or myocardial infarction, or cardiovascular death) using multivariable cause‐specific hazards models and added an interaction term to see if the association varies by immigration status. The absolute difference in the rate of cardiovascular events across income quintiles was less pronounced in immigrants than in long‐term residents: age‐ and sex‐adjusted rate per 1000 person‐years in quintile 1 versus quintile 5: 5.69 versus 4.10 in immigrants and 8.37 versus 5.87 in long‐term residents. In adjusted models, the interaction between immigration status and neighborhoodl evel was significant (Pinteraction

Background Corin plays important roles in the regulation of blood volume and pressure and cardiac function by activating natriuretic peptide pathway, exerting multiple cardioprotective effects. But the impacts of soluble corin on clinical outcomes after ischemic stroke are unclear. We aimed to investigate the associations between serum soluble corin and long‐term clinical outcomes after acute ischemic stroke. Methods and Results We measured the concentrations of serum soluble corin in 3162 participants (2010 men and 1152 women) from the China Antihypertensive Trial in Acute Ischemic Stroke. The clinical outcomes were recurrent stroke, cardiovascular events, all‐cause mortality, and unfavorable functional outcome within 24 months after stroke. Risk reclassification for study clinical outcomes of models with soluble corin were evaluated. Serum soluble corin was inversely associated with recurrent stroke, cardiovascular events, and unfavorable functional outcome after ischemic stroke. After adjusting for multiple covariates, each additional SD of log‐corin was associated with a 21% (95% CI, 11–30), 16% (95% CI, 6–26), and 12% (95% CI, 3–21) decreased risk for recurrent stroke, cardiovascular events, and unfavorable functional outcome, respectively. Furthermore, the addition of soluble corin to the basic model with conventional risk factors significantly improved risk discrimination for recurrent stroke, cardiovascular events, and the composite outcome of all‐cause mortality and cardiovascular events, as shown by C‐statistics (all P

Background The aim of this study was to assess how early‐adulthood body mass index (BMI) and waist circumference (WC) relate to long‐term cardiovascular structure, function, and prognosis in individuals without obesity and with low cardiovascular risk factor (CVRF) burden. Methods and Results A total of 2024 participants aged 18 to 30 from the CARDIA (Coronary Artery Risk Development in Young Adults) study, without obesity and with low CVRFs defined as the absence of cardiovascular disease (CVD), diabetes, hypertension, current smoking, and dyslipidemia were included. A CVRF‐optimal subgroup was also defined, with blood pressure

Background Although living alone versus with others is a key social element for cardiovascular prevention in diabetes, evidence is lacking about whether the benefit of intensive glycemic and blood pressure (BP) control differs by living arrangements. We thus aim to investigate heterogeneity in the joint effect of intensive glycemic and BP control on cardiovascular events by living arrangements among participants with diabetes. Methods and Results This study included 4731 participants with diabetes in the ACCORD‐BP (Action to Control Cardiovascular Risk in Diabetes‐Blood Pressure) trial. They were randomized into 4 study arms, each with glycated hemoglobin target (intensive,

Background Cardiovascular disease (CVD) is the most important comorbidity in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations not only contribute to COPD progression but may also elevate the risk of CVD. This study aimed to determine whether COPD exacerbations increase the risk of subsequent CVD events using up to 15 years of prospective longitudinal follow‐up data from the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study. Methods and Results The COPDGene study is a large, multicenter, longitudinal investigation of COPD, including subjects at enrollment aged 45 to 80 years with a minimum of 10 pack‐years of smoking history. Cox proportional hazards models and Kaplan‐Meier survival curves were used to assess the risk of a composite end point of CVD based on the COPD exacerbation rate. Frequent exacerbators exhibited a higher cumulative incidence of composite CVD end points than infrequent exacerbators, irrespective of the presence of CVD at baseline. After adjusting for covariates, frequent exacerbators still maintained higher hazard ratios (HRs) than the infrequent exacerbator group (without CVD: HR, 1.81 [95% CI, 1.47–2.22]; with CVD: HR, 1.92 [95% CI, 1.51–2.44]). This observation remained consistently significant in moderate to severe COPD subjects and the preserved ratio impaired spirometry population. In the mild COPD population, frequent exacerbators showed a trend toward more CVD events. Conclusions COPD exacerbations are associated with an increased risk of subsequent cardiovascular events in subjects with and without preexisting CVD. Patients with COPD experiencing frequent exacerbations may necessitate careful monitoring and additional management for subsequent potential CVD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00608764.

Background Cardiovascular disease is the leading cause of mortality in patients with kidney failure, and their risk of cardiovascular events is 10 to 20 times higher as compared with the general population. Methods and Results We evaluated 508 822 patients who initiated dialysis between January 1, 2005 and December 31, 2014 using the United States Renal Data System with linked Medicare claims. We determined hospitalization rates for cardiovascular events, defined by acute coronary syndrome, heart failure, and stroke. We examined the association of sex with outcome of cardiovascular events, cardiovascular death, and all‐cause death using adjusted time‐to‐event models. The mean age was 70±12 years and 44.7% were women. The cardiovascular event rate was 232 per thousand person‐years (95% CI, 231–233), with a higher rate in women than in men (248 per thousand person‐years [95% CI, 247–250] versus 219 per thousand person‐years [95% CI, 217–220]). Women had a 14% higher risk of cardiovascular events than men (hazard ratio [HR], 1.14 [95% CI, 1.13–1.16]). Women had a 16% higher risk of heart failure (HR, 1.16 [95% CI, 1.15–1.18]), a 31% higher risk of stroke (HR, 1.31 [95% CI, 1.28–1.34]), and no difference in risk of acute coronary syndrome (HR, 1.01 [95% CI, 0.99–1.03]). Women had a lower risk of cardiovascular death (HR, 0.89 [95% CI, 0.88–0.90]) and a lower risk of all‐cause death than men (HR, 0.96 [95% CI, 0.95–0.97]). Conclusions Among patients undergoing dialysis, women have a higher risk of cardiovascular events of heart failure and stroke than men. Women have a lower adjusted risk of cardiovascular mortality and all‐cause mortality.

Background Serum uric acid (UA) is correlated closely with traditional cardiovascular risk factors, which might interfere with the action of UA, in patients with coronary artery disease. We performed this study to evaluate the prognostic effect of UA levels in individuals with different numbers of standard modifiable cardiovascular risk factors (SMuRFs). Methods and Results In this prospective study, we consecutively enrolled 10 486 patients with coronary artery disease. They were stratified into 3 groups according to the tertiles of UA concentrations and, within each UA tertile, further classified into 3 groups by the number of SMuRFs (0–1 versus 2–3 versus 4). The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including death, myocardial infarction, stroke, and unplanned revascularization. Over a median follow‐up of 2.4 years, 1233 (11.8%) MACCEs were recorded. Patients with high UA levels developed significantly higher risk of MACCEs than those with low UA levels. In addition, UA levels were positively associated with MACCEs as a continuous variable. More importantly, in patients with 0 to 1 SMuRF, the risks of MACCEs were significantly higher in the high‐UA‐level group (adjusted hazard ratio [HR], 1.469 [95% CI, 1.197–1.804]) and medium‐UA‐level group (adjusted HR, 1.478 [95% CI, 1.012–2.160]), compared with the low‐UA‐level group, whereas no significant association was found between UA levels and the risk of MACCEs in participants with 2 to 3 or 4 SMuRFs. Conclusions In patients with coronary artery disease who received evidence‐based secondary prevention therapies, elevated UA levels might affect the prognosis of individuals with 0 to 1 SMuRF but not that of individuals with ≥2 SMuRFs.

Background Residual risk of cardiovascular events and plaque progression remains despite reduction in low‐density lipoprotein cholesterol. Factors contributing to residual risk remain unclear. The authors examined the role of eicosapentaenoic acid and docosahexaenoic acid in coronary plaque regression and its predictors. Methods and Results A total of 240 patients with stable coronary artery disease were randomized to eicosapentaenoic acid plus docosahexaenoic acid (3.36 g/d) or none for 30 months. Patients were stratified by regression or progression of coronary fatty plaque measured by coronary computed tomographic angiography. Cardiac events were ascertained. The mean±SD age was 63.0±7.7 years, mean low‐density lipoprotein cholesterol level was

Background The longitudinal trajectories of renal function have been associated with cardiovascular events in patients with chronic kidney disease (CKD). However, the change pattern of renal function in those without CKD has not yet been reported. We aim to explore patterns of renal function change in a non‐CKD population and its associated risks with cardiovascular outcomes. Methods and Results The present study analyzed data from 4 prospective cohorts and was restricted to participants without baseline CKD. The primary outcome was major adverse cardiovascular events, defined as a composite of myocardial infarction, chronic heart failure, stroke, and cardiovascular deaths. We used a group‐based trajectory model to identify latent groups and analyzed the associated risk with Cox regression models. The complete dates of this study were June 1, 2020, through January 1, 2021. The final sample comprised 23 760 participants (mean age, 58.63 [9.12] years, 10 618 men, and 17 799 White participants). During 20.56 years follow‐up, 8328 (35.05%) first major adverse cardiovascular events happened. Four trajectories in estimated glomerular renal function and 3 patterns of CKD progression were identified. Compared with subjects assigned to class I trajectory (high to mildly decreased group), the adjusted hazard ratios of major adverse cardiovascular events for class II (normal to mildly decreased group), class III (normal to moderately decreased group), and class IV (mildly to severely decreased group) were 1.11 (95% CI, 1.01–1.23), 1.27 (95% CI, 1.14–1.40), and 1.56 (95% CI, 1.38–1.77), respectively. Likewise, participants assigned to the slow and rapid progression groups had elevated HRs for major adverse cardiovascular events (1.75 [95% CI, 1.39–2.21] and 2.19 [95% CI, 1.68–2.86], respectively) when compared with the stable group. Findings were generally consistent in stratification analysis, but significant interaction effects by age and smoking status were detected. Conclusions In this study, we identified unique trajectory groups for renal function. These findings may signal an underlying high‐risk population and inspire future studies on individualized risk management.

Background Whether visit‐to‐visit systolic blood pressure (SBP) variability can predict major adverse cardiovascular events (MACE) in patients with chronic kidney disease is unclear. Methods and Results We investigated the relationship between SDs of visit‐to‐visit SBP variability during the first year of enrollment and MACE among 1575 participants from KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into 3 groups according to tertiles of visit‐to‐visit SBP variability (SD). The study end point was MACE, defined as a composite of nonfatal myocardial infarction, unstable angina, revascularization, nonfatal stroke, hospitalization for heart failure, or cardiac death. During 6748 patient‐years of follow‐up (median, 4.2 years), MACE occurred in 64 participants (4.1%). Compared with the lowest tertile of visit‐to‐visit SBP variability (SD), the hazard ratios (HRs) for the middle and the highest tertile were 1.64 (95% CI, 0.80–3.36) and 2.23 (95% CI, 1.12–4.44), respectively, in a multivariable cause‐specific hazard model. In addition, the HR associated with each 5‐mm Hg increase in visit‐to‐visit SBP variability (SD) was 1.21 (95% CI, 1.01–1.45). This association was consistent in sensitivity analyses with 2 additional definitions of SBP variability determined by the coefficient of variation and variation independent of the mean. The corresponding HRs for the middle and highest tertiles were 2.11 (95% CI, 1.03–4.35) and 2.28 (95% CI, 1.12–4.63), respectively, in the analysis with the coefficient of variation and 1.76 (95% CI, 0.87–3.57) and 2.04 (95% CI, 1.03–4.03), respectively, with the variation independent of the mean. Conclusions Higher visit‐to‐visit SBP variability is associated with an increased risk of MACE in patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.

Background Patients with acute coronary syndrome (ACS) are recognized by guidelines as remaining at high risk for adverse outcomes. Evidence from contemporary, representative ACS populations in a clinical practice setting is necessary to identify subgroups and strategies for improving patient outcomes. We aimed to describe event rates and risk factors in an ACS population over prolonged follow‐up for cardiovascular end points. Methods and Results We identified 239 234 patients in the Optum Research Database (57.2% men; mean [standard deviation] age, 69.2 [12.2] years) with evidence of an ACS hospitalization (index ACS) during January 1, 2005 through December 30, 2018. Subgroups were based on index ACS event (myocardial infarction/unstable angina and revascularization status) and the Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention. The 5‐year event rate for the primary end point representing nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death was 33.4% (95% CI, 33.1%–33.7%; P

Background The impact of chronic kidney disease (CKD) on the prognostic utility of cardiovascular biomarkers in high‐risk patients remains unclear. Methods and Results We performed a multicenter, prospective cohort study of 3255 patients with suspected or known coronary artery disease (CAD) to investigate whether CKD modifies the prognostic utility of cardiovascular biomarkers. Serum levels of cardiovascular and renal biomarkers, including soluble fms‐like tyrosine kinase‐1 (sFlt‐1), N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), high‐sensitivity cardiac troponin‐I (hs‐cTnI), cystatin C, and placental growth factor, were measured in 1301 CKD and 1954 patients without CKD. The urine albumin to creatinine ratio (UACR) was measured in patients with CKD. The primary outcome was 3‐point MACE (3P‐MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The secondary outcomes were all‐cause death, cardiovascular death, and 5P‐MACE defined as a composite of 3P‐MACE, heart failure hospitalization, and coronary/peripheral artery revascularization. After adjustment for clinical confounders, sFlt‐1, NT‐proBNP, and hs‐cTnI, but not other biomarkers, were significantly associated with 3P‐MACE, all‐cause death, and cardiovascular death in the entire cohort and in patients without CKD. These associations were still significant in CKD only for NT‐proBNP and hs‐cTnI. NT‐proBNP and hs‐cTnI were also significantly associated with 5P‐MACE in CKD. The UACR was not significantly associated with any outcomes in CKD. NT‐proBNP and hs‐cTnI added incremental prognostic information for all outcomes to the model with potential clinical confounders in CKD. Conclusions NT‐proBNP and hs‐cTnI were the most powerful prognostic biomarkers in patients with suspected or known CAD and concomitant CKD.

Background The long‐term burden of cardiovascular disease after repair of coarctation of the aorta (CoA) has not been elucidated. We aimed to determine the incidence of and risk factors for cardiovascular events in adult patients with repaired CoA. Additionally, mortality rates were compared between adults with repaired CoA and the general population. Methods and Results Using the Dutch Congenital Corvitia (CONCOR) registry, patients aged ≥16 years with previous surgical or transcatheter CoA repair from 5 tertiary referral centers were included. Cardiovascular events were recorded, comprising coronary artery disease, stroke/transient ischemic attack, aortic complications, arrhythmias, heart failure hospitalizations, endocarditis, and cardiovascular death. In total, 920 patients (median age, 24 years [range 16–74 years]) were included. After a mean follow‐up of 9.3±5.1 years, 191 patients (21%) experienced at least 1 cardiovascular event. A total of 270 cardiovascular events occurred, of which aortic complications and arrhythmias were most frequent. Older age at initial CoA repair (hazard ratio [HR], 1.017; 95% CI, 1.000–1.033 [P=0.048]) and elevated left ventricular mass index (HR, 1.009; 95% CI, 1.005–1.013 [P

Background Arterial stiffness is an important predictor of cardiovascular events; however, indexes for measuring arterial stiffness have not been widely incorporated into routine clinical practice. This study aimed to determine whether the cardio‐ankle vascular index (CAVI), based on the blood pressure–independent stiffness parameter β and reflecting arterial stiffness from the origin of the ascending aorta, is a good predictor of cardiovascular events in patients with cardiovascular disease risk factors in a large prospective cohort. Methods and Results This multicenter prospective cohort study, commencing in May 2013, with a 5‐year follow‐up period, included patients (aged 40‒74 years) with cardiovascular disease risks. The primary outcome was the composite of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. Among 2932 included patients, 2001 (68.3%) were men; the mean (SD) age at diagnosis was 63 (8) years. During the median follow‐up of 4.9 years, 82 participants experienced primary outcomes. The CAVI predicted the primary outcome (hazard ratio, 1.38; 95% CI, 1.16‒1.65; P

Background It is unclear what office blood pressure (BP) is the optimal treatment target range in patients with hypertension. Methods and Results Using the Korean National Health Insurance Service database, we extracted the data on 479 359 patients with hypertension with available BP measurements and no history of cardiovascular events from 2002 to 2011. The study end point was major cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, or stroke. This cohort study evaluated the association of BP levels (

Background The FHOD3 (formin homology 2 domain‐containing 3) gene has recently been identified as a causative gene of hypertrophic cardiomyopathy (HCM). However, the pathogenicity of FHOD3 variants remains to be evaluated. This study analyzed the spectrum of FHOD3 variants in a large HCM and control cohort, and explored its correlation with the disease. Methods and Results The genetic analysis of FHOD3 was performed using the whole exome sequencing data from 1000 patients with HCM and 761 controls without HCM. A total of 37 FHOD3 candidate variants were identified, including 25 missense variants and 2 truncating variants. In detail, there were 27 candidate variants detected in 33 (3.3%) patients with HCM, which was significantly higher than in the 12 controls (3.3% versus 1.6%; odds ratio, 2.13; P

Background To determine whether differences in body composition contribute to sex differences in cardiovascular disease (CVD) mortality, we investigated the relationship between components of body composition and CVD mortality in healthy men and women. Methods and Results Dual energy x‐ray absorptiometry body composition data from the National Health and Nutrition Examination Survey 1999–2004 and CVD mortality data from the National Health and Nutrition Examination Survey 1999–2014 were evaluated in 11 463 individuals 20 years of age and older. Individuals were divided into 4 body composition groups (low muscle mass–low fat mass—the referent; low muscle–high fat; high muscle–low fat, and high muscle–high fat), and adjusted competing risks analyses were performed for CVD versus non‐CVD mortality. In women, high muscle/high fat mass was associated with a significantly lower adjusted CVD mortality rate (hazard ratio [HR], 0.58; 95% CI, 0.39–0.86; P=0.01), but high muscle/low fat mass was not. In men, both high muscle–high fat (HR, 0.74; 95% CI, 0.53–1.04; P=0.08) and high muscle–low fat mass (HR, 0.40; 95% CI, 0.21–0.77; P=0.01) were associated with lower CVD. Further, in adjusted competing risks analyses stratified by sex, the CVD rate in women tends to significantly decrease as normalized total fat increase (total fat fourth quartile: HR, 0.56; 95% CI, 0.34–0.94; P

Background Inflammation levels are lower in East Asians than in Western people. We studied the association between high‐sensitivity hs‐CRP (C‐reactive protein) and adverse outcomes in Korean patients with chronic kidney disease. Methods and Results We included 2018 participants from the KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) between April 2011 and February 2016. The primary outcome was a composite of extended major cardiovascular events (eMACE) or all‐cause mortality. The secondary end points were separate outcomes of eMACE, all‐cause death, and adverse kidney outcome. We also evaluated predictive ability of hs‐CRP for the primary outcome. The median hs‐CRP level was 0.60 mg/L. During the mean follow‐up of 3.9 years, there were 125 (6.2%) eMACEs and 80 (4.0%) deaths. In multivariable Cox analysis after adjustment of confounders, there was a graded association of hs‐CRP with the primary outcome. The hazard ratios for hs‐CRPs of 1.0 to 2.99 and ≥3.0 mg/L were 1.33 (95% CI, 0.87–2.03) and 2.08 (95% CI, 1.30–3.33) compared with the hs‐CRP of

Background The long‐term prognosis of refractory hypertension (RfHT), defined as failure to control blood pressure (BP) levels despite an antihypertensive treatment with ≥5 medications including a diuretic and mineraloreceptor antagonist, has never been evaluated. Methods and Results In a prospective cohort study with 1576 patients with resistant hypertension, patients were classified as refractory or nonrefractory based on uncontrolled clinic (or office) and ambulatory BPs during the first 2 years of follow‐up. Multivariate Cox analyses examined the associations between the diagnosis of RfHT and the occurrence of total cardiovascular events (CVEs), major adverse CVEs, and cardiovascular and all‐cause mortality, after adjustments for other risk factors. In total, 135 patients (8.6%) had RfHT by uncontrolled ambulatory BPs and 167 (10.6%) by uncontrolled clinic BPs. Over a median Follow‐Up of 8.9 years, 338 total CVEs occurred (288 major adverse CVEs, including 124 myocardial infarctions, and 96 strokes), and 331 patients died, 196 from cardiovascular causes. The diagnosis of RfHT, using either classification by clinic or ambulatory BPs, was associated with significantly higher risks of major adverse CVEs, cardiovascular mortality, and stroke incidence, with hazard ratios varying from 1.54 to 2.14 in relation to patients with resistant nonrefractory hypertension; however, the classification based on ambulatory BPs was better in identifying higher risk patients than the classification based on clinic BP levels. Conclusions Patients with RfHT, particularly when defined by uncontrolled ambulatory BP levels, had higher risks of major adverse CVEs and mortality in relation to patients with resistant but nonrefractory hypertension, supporting the concept of refractory hypertension as a true extreme phenotype of antihypertensive treatment failure.

Background Epidemiological studies have reported discrepant findings on the relationship between education level and outcomes after stroke. We aimed to prospectively investigate the relationship between education level and mortality, recurrent stroke, and cardiovascular events in Chinese patients with ischemic stroke. Methods and Results We included 3861 participants from the China Antihypertensive Trial in Acute Ischemic Stroke. Education level was categorized as illiteracy, primary school, middle school, and college. Study outcomes were all‐cause mortality, stroke‐specific mortality, recurrent stroke, and cardiovascular events within 2 years after ischemic stroke. A meta‐analysis was conducted to incorporate the results of the current study and previous other studies on the association of education level with outcomes after stroke. Within 2 years after ischemic stroke, there were 327 (8.5%) all‐cause deaths, 264 (6.8%) stroke‐specific deaths, 303 (7.9%) recurrent strokes, and 364 (9.4%) cardiovascular events, respectively. The Kaplan–Meier curves showed that patients with the lowest education level had the highest cumulative incidence rates of all‐cause mortality, stroke‐specific mortality, and cardiovascular events (log‐rank P≤0.01). After adjusted for covariates, hazard ratios and 95% CIs of illiteracy versus college education were 2.79 (1.32–5.87) for all‐cause mortality, 3.68 (1.51–8.98) for stroke‐specific mortality, 2.82 (1.20–6.60) for recurrent stroke, and 3.46 (1.50–7.95) for cardiovascular events. The meta‐analysis confirmed the significant association between education status and mortality after stroke (pooled relative risk for lowest versus highest education level, 1.24 [95% CI, 1.05–1.46]). Conclusions Low education level was significantly associated with increased risk of mortality, recurrent stroke, and cardiovascular events after ischemic stroke, independently of established risk factors. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01840072.

Background FGF21 (fibroblast growth factor 21), a novel hepatokine regulating lipid metabolism, has been linked to atherosclerotic disease. However, whether this relationship exists in patients without nonalcoholic fatty liver disease is unclear. We assessed the association between serum FGF21 levels and atherosclerosis in patients without nonalcoholic fatty liver disease, and investigated whether baseline FGF21 could predict incident atherosclerotic cardiovascular disease in a 7‐year prospective cohort. Methods and Results Baseline serum FGF21 was measured in a cross‐sectional cohort of 371 patients with type 2 diabetes mellitus without nonalcoholic fatty liver disease (determined by hepatic magnetic resonance spectroscopy), and in a population‐based prospective cohort of 705 patients from the Shanghai Diabetes Study. In the cross‐sectional study, FGF21 was significantly higher in patients with than in those without subclinical carotid atherosclerosis (P

Background Childhood adversity and trauma have been shown to be associated with poorer cardiovascular disease (CVD) outcomes in adulthood. However, longitudinal studies of this association are rare. Methods and Results Our study used the CARDIA (Coronary Artery Risk Development in Young Adults) Study, a longitudinal cohort that has followed participants from recruitment in 1985–1986 through 2018, to determine how childhood psychosocial environment relates to CVD incidence and all‐cause mortality in middle age. Participants (n=3646) completed the Childhood Family Environment (CFE) questionnaire at the year 15 (2000–2001) CARDIA examination and were grouped by high, moderate, or low relative CFE adversity scores. We used sequential multivariable regression models to estimate hazard ratios of incident (CVD) and all‐cause mortality. Participants were 25.1±3.6 years old, 47% black, and 56% female at baseline and 198 participants developed CVD (17.9 per 10 000 person‐years) during follow‐up. CVD incidence was >50% higher for those in the high CFE adversity group compared with those in the low CFE adversity group. In fully adjusted models, CVD hazard ratios (95% CI) for participants who reported high and moderate CFE adversity versus those reporting low CFE adversity were 1.40 (0.98–2.11) and 1.25 (0.89–1.75), respectively. The adjusted hazard ratios for all‐cause mortality was 1.68 (1.17–2.41) for those with high CFE adversity scores and 1.55 (1.11–2.17) for those with moderate CFE adversity scores. Conclusions Adverse CFE was associated with CVD incidence and all‐cause mortality later in life, even after controlling for CVD risk factors in young adulthood.

Background VEGF‐D (vascular endothelial growth factor D) and VEGF‐C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF‐C level is inversely and independently associated with all‐cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF‐D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF‐D was measured. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin‐I, and high‐sensitivity C‐reactive protein), and VEGF‐C, the VEGF‐D level was significantly associated with all‐cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF‐D, either alone or in combination with VEGF‐C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all‐cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF‐D value seems to independently predict all‐cause mortality.

Background Although several studies have indicated that lipoprotein(a) is a useful prognostic predictor for patients following percutaneous coronary intervention (PCI), previous observations have somewhat been limited by either small sample size or short‐term follow‐up. Hence, this study aimed to evaluate the impact of lipoprotein(a) on long‐term outcomes in a large cohort of stable coronary artery disease patients after PCI. Methods and Results In this multicenter and prospective study, we consecutively enrolled 4078 stable coronary artery disease patients undergoing PCI from March 2011 to March 2016. They were categorized according to both the median of lipoprotein(a) levels and lipoprotein(a) values of

Background Excess adiposity, which affects 69% of US adults, increases coronary heart disease (CHD) risk in an association that manifests below conventional obesity cut points. The population‐level impact on CHD risk that is attainable through modest adiposity reductions in populations is not well characterized. We estimated the effect of hypothetical reductions in both body mass index (BMI) and waist circumference (WC) on CHD incidence. Methods and Results The study population included 13 610 ARIC (Atherosclerosis Risk in Communities) participants. Our hypothetical reduction in BMI or WC was applied relative to the temporal trend, with no hypothetical reduction among those with BMI >24 or WC >88 cm, respectively. This threshold for hypothetical reduction is near the clinical guidelines for excess adiposity. CHD risk differences compared the hypothetical reduction with no reduction. Sensitivity analysis was conducted to estimate the effect of applying the hypothetical BMI reduction at the established overweight cut point of 25. Cumulative 12‐year CHD incidence with no intervention was 6.3% (95% CI, 5.9–6.8%). Risk differences following the hypothetical BMI and WC reductions were −0.6% (95% CI, −1.0% to −0.1%) and −1.0% (95% CI, −1.4% to −0.5%), respectively. These results were robust for the sensitivity analyses. Consequently, we estimated that this hypothetical reduction of 5% in BMI and WC, respectively, could have prevented 9% and 16%, respectively, of the CHD events occurring in this study population over 12 years, after adjustment for established CHD risk factors. Conclusions Meaningful CHD risk reductions could derive from modest reductions in adiposity attainable through lifestyle modification.

Background Information is scarce regarding effects of antihypertensive medication on blood pressure variability (BPV) and associated clinical outcomes. We examined whether antihypertensive treatment changes BPV over time and whether such change (decline or increase) has any association with long‐term mortality in an elderly hypertensive population. Methods and Results We used data from a subset of participants in the Second Australian National Blood Pressure study (n=496) aged ≥65 years who had 24‐hour ambulatory blood pressure recordings at study entry (baseline) and then after a median of 2 years while on treatment (follow‐up). Weighted day‐night systolic BPV was calculated for both baseline and follow‐up as a weighted mean of daytime and nighttime blood pressure standard deviations. The annual rate of change in BPV over time was calculated from these BPV estimates. Furthermore, we classified both BPV estimates as high and low based on the baseline median BPV value and then classified BPV changes into stable: low BPV, stable: high BPV, decline: high to low, and increase: low to high. We observed an annual decline (mean±SD: −0.37±1.95; 95% CI, −0.54 to −0.19; P

Background Body mass index and waist circumference (WC) are commonly used metrics that reflect general obesity and abdominal obesity. However, the impact of general and abdominal obesity discrepancies on the risk for major adverse cardiac events (MACE) is less explored. Methods and Results The study population was derived from the Korean National Health Insurance Service‐Health Screening Cohort. Among 315 982 participants aged 40 years or older who underwent health examinations between 2008 and 2009, body mass index and WC were used to determine the obesity status. The participants were followed from January 1, 2010 for MACE until December 31, 2015. Cox proportional hazards models were used to evaluate the association of obesity and the risk of MACE. Compared with men who were not obese, those with abdominal obesity without general obesity (adjusted hazard ratio (aHR) 1.29, 95% CI 1.16–1.43), and general and abdominal obesity (aHR 1.20, 95% CI 1.12–1.29) had elevated risk of MACE, while those with general obesity without abdominal obesity (aHR 1.06, 95% CI 0.98–1.16) did not. Similarly, women with abdominal obesity without general obesity (aHR 1.13, 95% CI 1.03–1.24) and those with general and abdominal obesity (aHR 1.15, 95% CI 1.06–1.25) had increased risk of MACE, while those with general obesity without abdominal obesity (aHR 1.07, 95% CI 0.88–1.30) did not. Conclusions Abdominal obesity without general obesity was associated with an elevated risk of major cardiovascular outcomes while general obesity without abdominal obesity did not. Concurrent determination of body mass index and WC may be beneficial for the accurate determination of future cardiovascular risk.

Background The value of glycemic control and preexisting cardiovascular disease in determining the risk of major cardiovascular events (MACE) in type 2 diabetes mellitus is uncertain. Intensive glucose control trials suggest that the 9% lower risk of MACE associated with intensive glycemic control, as compared with conventional glycemic control, is only driven by patients with type 2 diabetes mellitus without cardiovascular disease at baseline. Methods and Results We did a meta‐analysis of cardiovascular outcome trials dividing patients with or without preexisting cardiovascular disease; we found that the lower risk of MACE is confined to patients with cardiovascular disease at baseline. Compared with placebo, the use of both glucagon‐like peptide‐1 receptor agonists and sodium‐glucose cotransporter‐2 inhibitors was associated with a significant 14% lower MACE risk in patients with preexisting cardiovascular disease and with a nonsignificant 2% higher MACE risk in those without preexisting cardiovascular disease (P for interaction=0.021). The meta‐regression analysis of all 12 trials demonstrated a significant (P=0.002) association between reductions of glycated hemoglobin in glycated hemoglobin A1C. Accordingly, the reduction of MACE expected if all cardiovascular outcome trials had achieved a 0.9% glycated hemoglobin reduction would have been 33%. Routine clinical care data complement the results of cardiovascular outcome trials but with some differences: the lower risk of MACE with sodium‐glucose cotransporter‐2 inhibitor use is evident in patients with type 2 diabetes mellitus with or without preexisting cardiovascular disease. Conclusions Sodium‐glucose cotransporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists should be included in the therapeutic plan of patients with type 2 diabetes mellitus and overt cardiovascular disease, with due attention paid to improvement of glycemic control, which may amplify their benefit on MACE.

Background Dilatation of the basilar artery (BA) has been recognized as a predictor of cardiovascular events (CVEs). However, it is unclear if the longitudinal change in BA diameter (ΔBA) is associated with CVEs. Methods and Results In a cohort of Japanese participants with vascular risk factors in an observational study, we evaluated the relationship of ΔBA to CVEs and the time course of the BA diameter. The short axis of the BA diameter was measured at the midpons level in T2‐weighted images. Brain magnetic resonance imaging measurements included cerebral small‐vessel disease, lacunars, and white matter hyperintensities. First, 493 patients were analyzed by the time‐dependent Cox proportional hazards model to evaluate the association between ΔBA and CVEs, with adjustment for age, sex, vascular risk factors, and magnetic resonance imaging parameters. Second, we assessed the longitudinal ΔBA in 164 patients who underwent long‐term follow‐up magnetic resonance imaging, by linear regression analysis. In the mean follow‐up of 8.7 years, 105 patients developed CVEs. A smaller ΔBA was independently associated with the high incidence of CVEs (hazard ratio, 0.36; 95% CI, 0.16–0.78; P=0.010; n=493). After a mean interval of 9.4 years, the average ΔBA was 0.41±0.46 mm (excluding patients with fetal‐type circle of Willis). Progression of BA dilatation was associated with men but inversely associated with initial BA diameter and fetal‐type circle of Willis (n=164). Conclusions BA diameter increased over time (excluding the patients with fetal‐type circle of Willis), whereas ΔBA was inversely associated with the incidence of CVEs.

Background We hypothesized that measures of common carotid artery echolucency and grayscale texture features were associated with cardiovascular disease (CVD) risk factors and could predict CVD events. Methods and Results Using a case‐cohort design, we measured common carotid artery ultrasound images from 1788 participants in Exam 1 of the MESA study (Multi‐Ethnic Study of Atherosclerosis) to derive 4 grayscale features: grayscale median, entropy, gray level difference statistic‐contrast, and spatial gray level dependence matrices‐angular second moment. CVD risk factor associations were determined by linear regression. Cox proportional hazard models with inverse selection probability weighting and adjustments for age, sex, race/ethnicity, CVD risk factors, and C‐reactive protein were used to determine if standardized values for grayscale median, entropy, gray level difference statistic‐contrast, and spatial gray level dependence matrices‐angular second moment could predict incident coronary heart disease, stroke, and total CVD events over a median 13 years follow‐up. Participants were mean (SD) 63.1 (10.3) years of age, 52.6% female, 32.1% white, 27.8% black, 23.3% Hispanic, and 16.8% Chinese. There were 283 coronary heart disease, 120 stroke, and 416 CVD events. Several associations of grayscale features with CVD risk factors were identified. In fully adjusted models, higher gray level difference statistic‐contrast was associated with a lower risk of incident coronary heart disease (hazard ratio 0.82, 95% CI 0.71–0.94, padj=0.005) and CVD events (hazard ratio 0.87, 95% CI 0.77–0.98, padj=0.018); higher spatial gray level dependence matrices‐angular second moment was associated with a higher risk of CVD events (hazard ratio 1.09, 95% CI 1.00–1.19, padj=0.044). Conclusions Gray level difference statistic‐contrast and spatial gray level dependence matrices‐angular second moment predicted CVD events independent of risk factors, indicating their potential use as biomarkers to assess future CVD risk.

Background The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular disease. However, the relationships of vascular endothelial growth factor‐C (VEGF‐C), a central player in lymphangiogenesis, with mortality and cardiovascular events in patients with suspected or known coronary artery disease are unknown. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The primary predictor was serum levels of VEGF‐C. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events defined as a composite of cardiovascular death, non‐fatal myocardial infarction, and non‐fatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for established risk factors, VEGF‐C levels were significantly and inversely associated with all‐cause death (hazard ratio for 1‐SD increase, 0.69; 95% confidence interval, 0.60–0.80) and cardiovascular death (hazard ratio, 0.67; 95% confidence interval, 0.53–0.87), but not with major adverse cardiovascular events (hazard ratio, 0.85; 95% confidence interval, 0.72–1.01). Even after incorporation of N‐terminal pro‐brain natriuretic peptide, contemporary sensitive cardiac troponin‐I, and high‐sensitivity C‐reactive protein into a model with established risk factors, the addition of VEGF‐C levels further improved the prediction of all‐cause death, but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within 1717 patients with suspected coronary artery disease. Conclusions In patients with suspected or known coronary artery disease, a low VEGF‐C value may independently predict all‐cause mortality.

Background Whether use of high‐intensity statins is more important than achieving low‐density lipoprotein cholesterol (LDL‐C) target remains controversial in patients with coronary artery disease. We sought to investigate the association between statin intensity and long‐term clinical outcomes in patients achieving treatment target for LDL‐C after percutaneous coronary intervention. Methods and Results Between February 2003 and December 2014, 1746 patients who underwent percutaneous coronary intervention and achieved treatment target for LDL‐C (50% reduction from baseline level) were studied. We classified patients into 2 groups according to an intensity of statin prescribed after index percutaneous coronary intervention: high‐intensity statin group (atorvastatin 40 or 80 mg, and rosuvastatin 20 mg, 372 patients) and non‐high‐intensity statin group (the other statin treatment, 1374 patients). The primary outcome was a composite of cardiac death, myocardial infarction, or stroke. Difference in time‐averaged LDL‐C during follow‐up was significant, but small, between the high‐intensity statin group and non‐high‐intensity statin group (59±13 versus 61±12 mg/dL; P=0.04). At 5 years, patients receiving high‐intensity statins had a significantly lower incidence of the primary outcome than those treated with non‐high‐intensity statins (4.1% versus 9.9%; hazard ratio, 0.42; 95% confidence interval, 0.23–0.79; P

Background In statin trials, men and women derived similar relative risk reductions in cardiovascular events per 39 mg/dL low‐density lipoprotein cholesterol (LDL‐C) reduction. We explored whether lower LDL‐C levels and greater LDL‐C percentage reductions than those achieved with statins are associated with reduced major adverse cardiovascular event (MACE) rates in women as well as men. Methods and Results Data pooled from 10 phase 3 ODYSSEY randomized trials (n=4983) comparing alirocumab with control (placebo/ezetimibe) were assessed for association between 39 mg/dL lower on‐treatment LDL‐C and percentage LDL‐C change from baseline, and MACE risk by sex, using multivariable Cox regression. Mean baseline LDL‐C was 135 mg/dL (women) and 121 mg/dL (men). Average on‐treatment LDL‐C levels with alirocumab, ezetimibe, and placebo were 71, 114, and 134 mg/dL, respectively, in women (n=1882) and 52, 93, and 122 mg/dL, respectively, in men (n=3090). Overall, 36.5% and 58.7% of women and men, respectively, achieved on‐treatment LDL‐C

BackgroundHospitalization for cardiovascular disease (CVD) is common among patients receiving maintenance dialysis, but patterns of readmissions following cardiovascular events are underexplored. Methods and ResultsIn this retrospective analysis of prevalent, Medicare‐eligible patients receiving dialysis in 2012–2013, all live‐discharge hospitalizations attributed to CVD were ascertained. Rates of all‐cause, CVD‐related, and non–CVD‐related readmissions and death in the ensuing 10 and 30 days were calculated. Multinomial logistic modeling was used to assess the relationship between potential explanatory factors and outcomes of interest. Among 142 210 analyzed hospitalizations, mean age at time of index CVD hospitalization was 64.9±14.1 years; 50.4% of index hospitalizations were for women, and 41.4% were for white patients. Fully 15.6% and 34.2% of CVD hospitalizations resulted in readmission within 10 and 30 days, respectively; less than half of readmissions were CVD related (42.5%, 10 days; 43.1%, 30 days). Death within 30 days, regardless of readmission, occurred after 4.5% of index hospitalizations; 51.2% were attributed to CVD. Compared with ages 65 to 69 years, younger age tended to be associated with increased readmission risk (adjusted relative risk for ages 18–44 years: 1.55; 95% confidence interval, 1.48–1.63). Readmission risk did not differ between white and black patients, but risk of death without readmission was markedly lower for black patients (relative risk: 0.60; 95% confidence interval, 0.55–0.67). ConclusionsRoughly 1 in 3 CVD hospitalizations resulted in 30‐day readmission; nearly 1 in 20 was followed by death within 30 days. Risk of death without readmission was higher for white than black patients, despite no difference in risk of readmission.

BackgroundThe association of short‐term variability of fasting plasma glucose (FPG) and mortality has been well investigated. However, the relationships between visit‐to‐visit variability of FPG over longer periods of follow‐up and cardiovascular disease (CVD) and all‐cause mortality are unclear. This study aimed to investigate these relationships. Methods and ResultsThe current analysis included 53 607 Chinese participants (mean age, 49.10 years) who were free of CVD in the Kailuan study. Participants were divided into 4 categories by quartiles of visit‐to‐visit variability of FPG. Visit‐to‐visit variability of FPG was defined as the coefficient of variation of 3 values of FPG that were measured from the examination periods of 2006 to 2007, 2008 to 2009, and 2010 to 2011. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for CVD and all‐cause mortality. After a mean follow‐up of 4.93 years, 4261 individuals developed CVD and 1545 individuals died. The incidence of CVD and all‐cause mortality was 5.04 and 5.85 per 1000 person‐years, respectively. After adjusting for mean FPG and other potential confounders, individuals in the highest quartile of variability of FPG compared with participants in the lowest quartile showed a 26% greater risk of developing CVD (hazard ratio, 1.26; 95% confidence interval, 1.08–1.47) and a 46% greater risk for all‐cause mortality (hazard ratio, 1.46; 95% confidence interval, 1.25–1.70). ConclusionsIndependent of mean FPG and other baseline parameters, elevated visit‐to‐visit variability of FPG significantly increases the risk of CVD and all‐cause mortality in the general population. Measuring long‐term visit‐to‐visit variability of FPG is helpful for predicting the risk for CVD and all‐cause mortality.

BackgroundGut microbiota is emerging as a novel risk factor for atherothrombosis, but the predictive role of gut‐derived lipopolysaccharide (LPS) is unknown. We analyzed (1) the association between LPS and major adverse cardiovascular events (MACE) in atrial fibrillation (AF) and (2) its relationship with adherence to a Mediterranean diet (Med‐diet). Methods and ResultsThis was a prospective single‐center study including 912 AF patients treated with vitamin K antagonists (3716 patient‐years). The primary end point was a composite of MACE. Baseline serum LPS, adherence to Med‐diet (n=704), and urinary excretion of 11‐dehydro‐thromboxane B2 (TxB2, n=852) were investigated. Mean age was 73.5 years; 42.9% were women. A total of 187 MACE (5.0% per year) occurred: 54, 59, and 74 in the first, second, and third tertile of LPS, respectively (log‐rank test P=0.004). Log‐LPS (hazard ratio 1.194, P=0.009), age (hazard ratio 1.083, P

BackgroundEnlargement of the proximal aorta is associated with aortic wall tissue remodeling, including fragmentation of the elastin fibers, increased synthesis of collagen, and calcification, all of which are associated with aortic wall stiffening. We hypothesized that the proximal aortic diameter (AoD) is associated with cardiovascular events in a community‐based cohort of blacks. Methods and ResultsWe investigated the associations between AoD and cardiovascular events among 3018 black participants (mean age, 55.9 years; 69% women) without past history of cardiovascular disease in the Jackson Heart Study. AoD was measured using echocardiography at the level of the sinuses of Valsalva at end diastole. Cardiovascular event was defined as incident myocardial infarction, fatal coronary artery disease, stroke, or heart failure hospitalization. Cox proportional hazards regression models were used to evaluate the association between baseline AoD and cardiovascular events. Over a median follow‐up of 8.3 years, there were 258 cardiovascular events (incident rate, 10.5 per 1000 person‐years). After adjustment for traditional risk factors, increased AoD was significantly associated with cardiovascular events (hazard ratio per 1‐cm increase, 1.72; 95% CI, 1.10–2.69; P

BackgroundHigher vegetable intake is consistently associated with lower atherosclerotic vascular disease (ASVD) events. However, the components responsible and mechanisms involved are uncertain. Nonnutritive phytochemicals may be involved. The objective of this study was to investigate the associations of total vegetable intake and types of vegetables grouped according to phytochemical constituents with ASVD mortality. Methods and ResultsThe cohort consisted of 1226 Australian women aged 70 years and older without clinical ASVD or diabetes mellitus at baseline (1998). Vegetable intakes were calculated per serving (75 g/d) and were also classified into prespecified types relating to phytochemical constituents. ASVD‐related deaths were ascertained from linked mortality data. During 15 years (15 947 person‐years) of follow‐up, 238 ASVD‐related deaths occurred. A 1‐serving increment of vegetable intake was associated with a 20% lower hazard of ASVD‐related death (multivariable‐adjusted hazard ratio, 0.80; 95% confidence interval, 0.69–0.94 [P=0.005]). In multivariable‐adjusted models for vegetable types, cruciferous (per 10‐g/d increase: hazard ratio, 0.87; 95% confidence interval, 0.81–0.94 [P

BackgroundAlthough 24‐hour blood pressure (BP) variability (BPV) is predictive of cardiovascular outcomes independent of absolute BP levels, it is not regularly assessed in clinical practice. One possible limitation to routine BPV assessment is the lack of standardized methods for accurately estimating 24‐hour BPV. We conducted a systematic review to assess the predictive power of reported BPV indexes to address appropriate quantification of 24‐hour BPV, including the average real variability (ARV) index. Methods and ResultsStudies chosen for review were those that presented data for 24‐hour BPV in adults from meta‐analysis, longitudinal or cross‐sectional design, and examined BPV in terms of the following issues: (1) methods used to calculate and evaluate ARV; (2) assessment of 24‐hour BPV determined using noninvasive ambulatory BP monitoring; (3) multivariate analysis adjusted for covariates, including some measure of BP; (4) association of 24‐hour BPV with subclinical organ damage; and (5) the predictive value of 24‐hour BPV on target organ damage and rate of cardiovascular events. Of the 19 assessed studies, 17 reported significant associations between high ARV and the presence and progression of subclinical organ damage, as well as the incidence of hard end points, such as cardiovascular events. In all these cases, ARV remained a significant independent predictor (P

BackgroundThe CHA2DS2‐VASc score predicts stroke in patients with atrial fibrillation and has been reported to have a prognostic role even in acute coronary syndrome patients. The Takotsubo syndrome is a condition that mimics acute coronary syndrome and may present several complications including stroke. We sought to assess the ability of CHA2DS2‐VASc score to predict adverse events in Takotsubo syndrome patients. Methods and ResultsOverall, 371 Takotsubo syndrome patients were enrolled in a prospective registry. Patients were divided into 3 groups according to the CHA2DS2‐VASc score: Group A (≤1), B (2–3), and C (≥4). The median CHA2DS2‐VASc score was 3 (interquartile range: 2–4). Overall, 9%, 42%, and 49% were included in Group A, B, and C, respectively. Follow‐up length was 26±20 months. The mortality rate was 6%, 7%, and 17% in Group A, B, and C, respectively (P=0.011). The stroke rate was 3% and not different among the 3 groups. Estimated major adverse cardiac and cerebrovascular events (the composite of death, myocardial infarction, and stroke) rates in the 3 groups were 6%, 9%, and 17% in Group A, B, and C, respectively (P=0.033). The CHA2DS2‐VASc score resulted as a predictor of major adverse cardiac and cerebrovascular events (odds ratio 2.1, 95% confidence interval, 1.2–3.6; P=0.01) and all‐cause mortality (odds ratio 1.5, 95% confidence interval, 1.2–1.9; P=0.001). ConclusionsIn Takotsubo syndrome, the CHA2DS2‐VASc score allows prediction of cardiovascular events and mortality at long‐term follow‐up.

BackgroundThe CHADS2 score has mainly been used to predict the likelihood of cerebrovascular accidents in patients with atrial fibrillation. However, increasing attention is being paid to this scoring system for risk stratification of patients with coronary artery disease. We investigated the value of the CHADS2 score in predicting cardiovascular/cerebrovascular events in coronary artery disease patients without atrial fibrillation. Methods and ResultsThis was a multicenter, observational cohort study. The subjects had been admitted to one of the participating institutions with coronary artery disease requiring percutaneous coronary intervention. We calculated the CHADS2 scores for 7082 patients (mean age, 69.7 years; males, 71.9%) without clinical evidence of atrial fibrillation. Subjects were subdivided into low‐ (0–1), intermediate‐ (2–3), and high‐score (4–6) groups and followed for 1 year. The end point was a composite of cardiovascular/cerebrovascular death, nonfatal myocardial infarction, and ischemic stroke at 1‐year follow‐up. Rates of triple‐vessel/left main trunk disease correlated positively with CHADS2 score categories. CHADS2 scores among single, double, and triple‐vessel/left main trunk groups were 2 (1–2), 2 (1–3), and 2 (2–3), respectively (P

BackgroundMean amplitude of glycemic excursion (MAGE) is commonly used to gauge the degree of glucose level fluctuations. MAGE plays a significant role in vascular endothelial dysfunction and cardiovascular events in patients with diabetes mellitus (DM), but its significance is not clear in non‐DM patients. Thus, we examined the impact of MAGE and vascular endothelial dysfunction on clinical outcomes in non‐DM patients with coronary artery disease. Methods and ResultsWe followed non‐DM patients (n=65) for 12 months who underwent percutaneous coronary intervention and assessed the relationship among MAGE, reactive hyperemia index (RHI) measured by reactive hyperemia peripheral arterial tonometry as endothelial function, and cardiovascular events. Cardiovascular events analyzed were cardiovascular death, myocardial infarction, unstable angina, and revascularizations. Compared with patients with MAGE

BackgroundPatients with unprovoked venous thromboembolism (VTE) are at an increased risk of mortality, but whether their cardiovascular risks also increase remains to be determined. We aimed to investigate the factors associated with overall mortality and major adverse cardiovascular events in patients with unprovoked VTE. Methods and ResultsWe identified 2154 patients newly diagnosed with unprovoked VTE from Taiwan's National Health Insurance Database between 2000 and 2013, excluding those with reversible etiologies, underlying cancer, or autoimmune diseases. These patients with VTE were compared with an age‐, sex‐, and cardiovascular risk‐matched cohort of 4308 controls. The risk of mortality and major adverse cardiovascular events in patients with VTE was 2.23 (CI, 1.93–2.57; P

BackgroundObesity and its association with reduced life expectancy are well established, with cardiovascular disease as one of the major causes of fatality. Metabolic surgery is a powerful intervention for severe obesity, resulting in improvement in comorbid diseases and in cardiovascular risk factors. This study investigates the relationship between metabolic surgery and long‐term cardiovascular events. Methods and ResultsA cohort of Roux‐en‐Y gastric bypass surgery (RYGB) patients was tightly matched by age, body mass index, sex, Framingham Risk Score, smoking history, use of antihypertension medication, diabetes mellitus status, and calendar year with a concurrent cohort of nonoperated control patients. The primary study end points of major cardiovascular events (myocardial infarction, stroke, and congestive heart failure) were evaluated using Cox regression. Secondary end points of longitudinal cardiovascular risk factors were evaluated using repeated‐measures regression. The RYGB and matched controls (N=1724 in each cohort) were followed for up to 12 years after surgery (overall median of 6.3 years). Kaplan–Meier analysis revealed a statistically significant reduction in incident major composite cardiovascular events (P=0.017) and congestive heart failure (0.0077) for the RYGB cohort. Adjusted Cox regression models confirmed the reductions in severe composite cardiovascular events in the RYGB cohort (hazard ratio=0.58, 95% CI=0.42–0.82). Improvements of cardiovascular risk factors (eg, 10‐year cardiovascular risk score, total cholesterol, high‐density lipoprotein, systolic blood pressure, and diabetes mellitus) were observed within the RYGB cohort after surgery. ConclusionsGastric bypass is associated with a reduced risk of major cardiovascular events and the development of congestive heart failure.

BackgroundHeart rate recovery (HRR) is a noninvasive assessment of autonomic dysfunction and has been implicated with risk of cardiovascular events and all‐cause mortality. However, evidence has not been systematically assessed. We performed a meta‐analysis of prospective cohort studies to quantify these associations in the general population. Methods and ResultsA literature search using 3 databases up to August 2016 was conducted for studies that reported hazard ratios with 95% CIs for the association between baseline HRR and outcomes of interest. The overall hazard ratios were calculated using a random‐effects model. There were 9 eligible studies in total, with 5 for cardiovascular events enrolling 1061 cases from 34 267 participants, and 9 for all‐cause mortality enrolling 2082 cases from 41 600 participants. The pooled hazard ratios associated with attenuated HRR versus fast HRR that served as the referent were 1.69 (95% CI 1.05–2.71) for cardiovascular events and 1.68 (95% CI 1.51–1.88) for all‐cause mortality. For every 10 beats per minute decrements in HRR, the hazard ratios were 1.13 (95% CI 1.05–1.21) and 1.09 (95% CI 1.01–1.19), respectively. Further analyses suggested that the associations observed between attenuated HRR and risk of fatal cardiovascular events and all‐cause mortality were independent of traditional metabolic factors for cardiovascular disease (all P

BackgroundLocal ancestry in relation to clinical cardiovascular events (CVEs) among African Americans can provide insight into their genetic susceptibility to the disease. Methods and ResultsWe examined local European ancestry (LEA) association with CVEs among 3000 African Americans from the Atherosclerosis Risk in Communities Study (ARIC). We estimated LEA using Local Ancestry Inference in adMixed Populations using Linkage Disequilibrium (LAMP‐LD) and examined its association with myocardial infarction, stroke, coronary heart disease and its composite and cardiovascular disease composite using logistic regression. Genome‐wide significance was achieved by 121 LEA regions in relation to myocardial infarction and 2 in relation to the cardiovascular disease composite. The LEA region downstream of 4q32.1 was significantly associated with 2 times higher odds of myocardial infarction (P=1.45×10−6). The LEA region upstream of 6q11.1 was associated with 0.37 times lower odds of fatal coronary heart disease (P=7.34×10−4), whereas the LEA region downstream of 21q21.1 was associated with 1.55 times higher odds of composite coronary heart disease (P=3.45×10−4). Association of LEA with stroke was observed in the region upstream of 6p22.3 with a 1.57 times higher odds of stroke (P=9.69×10−4). Likewise, the LEA region on 4q32.3 was associated with a 1.53 times higher odds of composite cardiovascular disease (P=3.04×10−4). We also found 20 of the LEA regions at previously significant cardiovascular disease single‐nucleotide polymorphisms to be associated with CVE in our study. ConclusionsFuture studies are needed to replicate and/or determine the causal variants driving our associations and explore clinical applications for those consistently associated with CVEs.

BackgroundWhile it is certain that some emergency department patients with acute drug overdose suffer adverse cardiovascular events (ACVE), predicting ACVE is difficult. The prognostic utility of the ECG for heterogeneous drug overdose patients remains to be proven. This study was undertaken to validate previously derived features of the initial ECG associated with ACVE in this population. Methods and ResultsWe performed a prospective validation cohort study to evaluate adult emergency department patients with acute drug overdose at 2 urban university hospitals over 5 years in whom an emergency department admission ECG was performed. Exclusion criteria were alternate diagnoses, anaphylaxis, chronic drug toxicity, and missing outcome data. ACVE was defined as any of the following: circulatory shock, myocardial injury, ventricular dysrhythmia, or cardiac arrest. Blinded cardiologists interpreted ECGs for previously derived predictors of ACVE (ectopy, QT prolongation, nonsinus rhythm, ischemia/infarction), QT dispersion, and prominent R wave in lead AVR. Of 589 patients who met inclusion criteria (48% male, mean age 42), there were 95 ACVEs (39 shock, 64 myocardial injury, 26 dysrhythmia, 16 cardiac arrest). The most common drug exposures were as follows: benzodiazepines, opioids, and acetaminophen. Previously derived criteria were highly predictive of ACVE, with QT correction >500 ms as the highest risk feature (OR 11.2, CI 4.6–27). ConclusionsThis study confirms that early ECG evaluation is essential to assess the cardiovascular prognosis and medical clearance of emergency department patients with acute drug overdose. Furthermore, this study validates previously derived high‐risk features of the admission ECG to risk stratify for ACVE in this patient population.

BackgroundLong‐term cardiovascular outcomes after sepsis in patients with chronic kidney disease are not well known. We aimed to examine the risk of subsequent cardiovascular events in patients with chronic kidney disease discharged after hospitalization for sepsis in Taiwan. Methods and ResultsUsing complete claims data for patients with chronic kidney disease from Taiwan's National Health Insurance Research Database, we identified patients with sepsis who survived hospitalization between 2000 and 2010. Each sepsis survivor was propensity score–matched to one nonsepsis hospitalized control patient. Cox regression models were used to estimate the hazard ratios (HRs) of clinical outcomes, including major adverse cardiovascular events (myocardial infarction and ischemic stroke), hospitalization for heart failure, and all‐cause death. Among 66 961 sepsis survivors, the incidence rates of all‐cause mortality and major adverse cardiovascular events during the study period were 288.51 and 47.05 per 1000 person‐years, respectively. In comparison with matched hospitalized nonsepsis control patients, sepsis survivors had greater risks of major adverse cardiovascular events (HR, 1.42; 95% CI, 1.37–1.47), myocardial infarction (HR, 1.39; 95% CI, 1.32–1.47), ischemic stroke (HR, 1.46; 95% CI, 1.40–1.52), hospitalization for heart failure (HR, 1.55; 95% CI, 1.51–1.59), and all‐cause mortality (HR, 1.56; 95% CI, 1.54–1.58). The results remained unchanged in analyses of several subgroups of patients, and were similar in analyses accounting for the competing risk of death. ConclusionsOur findings highlight the association of sepsis with a significantly increased long‐term risk of cardiovascular events among survivors in the chronic kidney disease population.