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Epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT) are anatomically close to the myocardium and may influence cardiovascular pathology. Thus, in this study, we aim to assess whether EAT and PAT volumes were associated with coronary artery calcification score (CCS) in patients with suspected coronary artery disease (CAD), especially in overweight and obese individuals.We included consecutive patients with suspected CAD in whom EAT volume, PAT volume, and CCS were measured via computed tomography between September 2015 and June 2017 at the Affiliated Hospital of Chengde Medical University, China. Logistic regression models were applied to analyze the risk factors for CCS ≥ 100 Agatston units (AU) and in different body mass index (BMI) subgroups.EAT and PAT volumes were noted to be higher in people with BMI ≥ 24 kg/m

BackgroundThe C1q/TNF-related protein (CTRP) family affects inflammation regulation, energy metabolism, and insulin signaling. However, their role in acute coronary syndrome (ACS) development is unclear. In this cross-sectional study, we aimed to investigate the association between CTRP family and ACS.MethodsWe enrolled 289 consecutive inpatients with suspected ACS. Serum CTRP family, tumor necrosis factor-α (TNF-α), and adiponectin (ADP) levels were assessed using enzyme-linked immunosorbent assay (ELISA). Multivariate logistic regression and subgroup analyses were used to assess risk factors for ACS. Spearman's tests were used to analyze correlations between CTRP family and continuous variables.ResultsSerum CTRP family levels differed significantly between ACS and Control groups (p < 0.05). After adjusting for confounding factors, CTRP family were independently associated with ACS (p < 0.05). The association between serum CTRP family levels and ACS was stable in various subgroups according to sex, age, diabetes mellitus, and dyslipidemia status (p for interaction > 0.05). Increasing tertiles of serum CTRP1 levels, significantly increased ACS risks, which decreased gradually with increasing CTRP2, CTRP12, and CTRP13 tertiles (p for trend < 0.05). Additionally, serum CTRP1, CTRP2, CTRP13, and CTRP15 levels were weakly correlated with the severity of coronary artery stenosis.ConclusionCTRP1 and CTRP5 were identified as independent ACS risk factors, whereas CTRP2, CTRP3, CTRP9, CTRP12, CTRP13, and CTRP15 were independent protective factors for ACS. CTRP family, especially CTRP1 and CTRP3 could be novel potential clinical biomarkers of ACS.

Although cardiovascular disease risk factors relate to COVID-19, the association of estimated atherosclerotic cardiovascular disease (ASCVD) risk with severe COVID-19 is not established. We examined the relation of the pooled-cohort ASCVD risk score to severe COVID-19 among 28,646 subjects from the National COVID Cohort Collaborative database who had positive SARS-CoV-2 test results from April 1, 2020 to April 1, 2021. In addition, 10-year ASCVD risk scores were calculated, and subjects were stratified into low-risk (=20%) groups. Severe COVID-19 outcomes (including death, remdesivir treatment, COVID-19 pneumonia, acute respiratory distress syndrome, and mechanical ventilation) occurring during follow-up were examined individually and as a composite in relation to ASCVD risk group across race and gender. Multiple logistic regression, adjusted for age, gender, and race, examined the relation of ASCVD risk group to the odds of severe COVID-19 outcomes. Our subjects had a mean age of 59.4 years; 14% were black and 57% were female. ASCVD risk group was directly related to severe COVID-19 prevalence. The adjusted odds ratio of the severe composite COVID-19 outcome by risk group (vs the low-risk group) was 1.8 (95% confidence interval 1.5 to 2.2) for the borderline-risk, 2.7 (2.3 to 3.2) for the intermediate-risk, and 4.6 (3.7 to 5.6) for the high-risk group. Black men and black women in the high-risk group showed higher severe COVID-19 prevalence compared with nonblack men and nonblack women. Prevalence of severe COVID-19 outcomes was similar in intermediate-risk black men and high-risk nonblack men (approximately 12%). In conclusion, although further research is needed, the 10-year ASCVD risk score in adults ages 40 to 79 years may be used to identify those who are at highest risk for COVID-19 complications and for whom more intensive treatment may be warranted.

Background: To estimate the population health impact of treating all US adults eligible for the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) with icosapent ethyl (IPE), we estimated (1) the number of ASCVD events and healthcare costs that could be prevented; and (2) medication costs. Methods: We derived REDUCE-IT eligible cohorts in (1) the National Health and Nutrition Examination Surveys (NHANES) 2009-2014 and (2) the Optum Research Database (ORD). Population sizes were obtained from NHANES and observed first event rates at five years (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, or coronary revascularization) were estimated from ORD. Hazard ratios from REDUCE-IT USA estimated events prevented with IPE. Total (i.e., first and recurrent) event rates were estimated from the REDUCE-IT USA subgroup, applying the treatment effect on total events observed in the entire REDUCE-IT trial. The National Inpatient Sample estimated facility and professional event costs and daily IPE treatment cost was approximated at $4.16. Results: We estimate 3.6 million US adults to be REDUCE-IT eligible, and an observed first event rate of 19.0% could be lowered to 13.1% with five years of IPE treatment, preventing 212,000 events (Table). We projected the annual IPE treatment cost for all eligible persons to be $5.5 billion, but saving $1.7 billion annually due to first events prevented (net annual cost $3.8 billion). The total five-year event rate (first and recurrent) could be reduced from 42.5% to 28.9% with five years of IPE therapy, preventing 490,000 events (net annual cost $2.3 billion). Conclusions: Treating all REDUCE-IT eligible US adults has substantial medication costs but could prevent a substantial number of ASCVD events and associated direct costs. Indirect cost savings by preventing events could outweigh much of the incurred direct costs.

Introduction Hypertriglyceridemia is associated with increased atherosclerotic cardiovascular disease (ASCVD) event risk, which persists even in statin-treated patients. The objective of this analysis was to estimate the prevalence of triglyceride (TG) levels ≥ 150 mg/dl in statin-treated adults with diabetes or ASCVD in the United States. Methods Laboratory data, medical history, and prescription data from 40,617 subjects who participated in the US National Health and Nutrition Examination Survey (NHANES) spanning 8 years (four 2-year surveys; 2007–2014) were analyzed. Patients included were ≥ 20 years old and had morning fasting (at least 8.5 h) TG values available. The proportion and weighted number of individuals in the US population with TG ≥ 150 mg/dl was calculated according to statin use, as well as in key subgroups of statin-treated patients including those with low-density lipoprotein cholesterol (LDL-C) levels

The role of NT-proBNP and hs-cTnT levels in predicting heart failure (HF) and cardiovascular disease (CVD) events in persons with prediabetes (pre-DM) and diabetes mellitus (DM) is not well-established. We examined the individual and combined relations of N-terminal natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) levels among asymptomatic adults with pre-DM and DM with the development of incident HF and CVD events. 5,584 participants with biomarker measures aged 45 to 84 years were included from the Multi-Ethnic Study of Atherosclerosis, of which 4,090 were normoglycemic, 799 had pre-DM, and 695 had DM at baseline and were followed for 12.4 ± 3.8 years. In those with DM, HF incidence rates per 1,000 person-years ranged from 3.2 to 39.4 across quartiles of NT-proBNP and 0.6 to 18.2 for hs-cTnT, respectively. Corresponding values for CVD incidence per 1,000 person-years ranged from 13.7 to 39.4 for NT-proBNP and 13.2 to 35.4 for hs-cTnT. Multivariate adjusted HRs were highest when both NT-proBNP and hs-cTnT were above versus below the median in those with pre-DM/DM (16.7 for incident HF and 2.1 for CVD events, both p

Background: Current US guidelines since 2013 have recommended statin use for high cardiovascular (CV) risk adults including those with atherosclerotic cardiovascular disease (ASCVD), regardless of LDL-C levels. Recent data among US population-representative adults regarding extent of LDL-C control in high CV risk persons are lacking. Methods: We examined among 4,484 US adults (representing 231 million) from the National Health and Nutrition Examination Surveys 2015-2018 the extent of statin use and remaining high LDL-C levels according to risk group as defined by the pooled cohort equation (PCE): low (< 20%), high risk without ASCVD (>20% 10-year risk), diabetes without ASCVD, and high and very high risk ASCVD as defined by the 2018 cholesterol management guideline based on multiple major ASCVD events or high risk conditions. Results: Overall, 18.9% (representing 43.7 million) of US adults were on statin therapy in our cohort; this varied across risk groups from 1.4% (low risk), 10.7% (intermediate risk), 26.2% (high risk without ASCVD), 48.8% (diabetes without ASCVD), 50.8% (ASCVD high risk) and 75.4% (ASCVD very high risk), with additional ezetimibe use 45% of high-risk primary prevention persons still have LDL-C > 100 mg/dL, >70% of those with DM to have LDL-C > 70 mg/dL, and >60% of high risk and >70% of very high-risk adults with ASCVD to have LDL-C > 70 mg/dL. Conclusions: Despite statin-focused guidelines since 2013, many US adults recommended for statin therapy are not on statins, and of those on statins, many have suboptimal LDL-C levels, warranting further LDL-C lowering with higher intensity statins and/or non-statin agents.

Introduction: Coronary artery calcium (CAC) is a measure of subclinical atherosclerosis and predicts cardiovascular disease (CVD) events. Higher parity, the number of live births, has been shown to relate to CVD. We examined whether parity is associated with progression of CAC as one pathway to CVD. Methods: We studied 2772 women aged 44 to 84 years free of CVD at baseline in the prospective Multi-Ethnic Study of Atherosclerosis. Parity was examined continuously as number of live births as well as by categories: 0-1 (reference), 2-3, and ≥4 in relation to change in CAC score from baseline to follow-up from repeat exams up to 11 years later. We used linear mixed effect models to account for repeated measures when assessing whether progression of CAC was associated with parity, adjusted for baseline CAC and other risk factors. Results: Women with higher parity had greater annualized progression of CAC scores (unadjusted p> 4 vs. 0-1 (p Conclusion: We show parity to be associated with the progression of CAC; this may help explain the increased CVD risk observed with higher parity and lends support to adding parity as a risk enhancing factor in women.

BACKGROUND Individuals with no history of coronary artery disease can develop acute coronary syndrome (ACS), often in the absence of major risk factors including low-density lipoprotein cholesterol (LDL-C). We identified risk factors and biomarkers that can help identify those at discordantly high risk of ACS with normal LDL-C using a novel validated coronary artery disease predictive algorithm (CADPA) incorporating biomarkers of endothelial injury. METHODS Five-year predicted ACS risk was calculated for 6392 persons using CADPA. Persons were classified as low (

Hypertriglyceridemia (HTG) is associated with increased cardiovascular disease (CVD) risk. However, the cost burden of HTG-related CVD in high-risk US adults on statins has not been well characterized.We estimated the HTG-related health care cost burden among US adults with CVD or diabetes taking statin therapy.We estimated population sizes and annual health care costs among US adults aged ≥45 years with diabetes or CVD taking statin therapy with normal triglycerides (TGs) defined as TG 150 mg/dL compared with those with HTG defined as TG ≥ 150 mg/dL. Population sizes were estimated from the 2007-2014 National Health and Nutrition Examination Surveys. Adjusted mean total annual health care costs in 2015 US dollars were estimated using the Optum Research Database. The annual total health care cost burden was estimated by multiplying the population size by the mean annual total incremental health care costs overall and within subgroups.There were 6.2 (95% confidence interval [CI], 5.4 - 7.1) million and 12.0 (95% CI, 11.1 - 12.9) million US adults aged ≥45 years with diabetes and/or CVD on statin therapy with TG ≥ 150 mg/dL and TG 150 mg/dL, respectively. The mean adjusted incremental total one-year health care costs in adults with TG ≥ 150 mg/dL compared with those with TG 150 mg/dL was $1730 (95% CI, $1160 - $2320). This leads to a projected annual incremental cost burden associated with HTG in patients with diabetes or CVD on statins of $10.7 billion (95% CI, $6.8 B - $14.6 B).In US adults on statins and at high risk for CVD, the health care costs associated with HTG are substantial.

Statin therapy remains the primary treatment for mixed dyslipidemia, even with moderate triglyceride (TG) elevations.We examined the prevalence of elevated TG levels in adults with and without statin use and the associated 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk.We studied 9593 US adults aged ≥20 years (219.9 million projected) in the US National Health and Nutrition Examination Surveys, 2007 to 2014. We determined the proportions of TG categories (150, 150-199, 200-499, and ≥500 mg/dL) according to statin use, as well as the 10-year estimated ASCVD risk and number of events.Among those not taking statin therapy, the prevalence of TG 150, 150 to 199, and ≥200 mg/dL was 75.3%, 12.8%, and 11.9%; among statin users, these proportions were 68.4%, 16.2%, and 15.4%, respectively. Among persons with low-density lipoprotein cholesterol100 mg/dL (or70 mg/dL in those with ASCVD), despite statin use, 27.7% had TG ≥ 150 mg/dL. The odds of TG ≥ 150 mg/dL in statin users was associated with greater age, higher body mass index, lower high-density lipoprotein cholesterol, higher low-density lipoprotein cholesterol, and diabetes. Estimated mean 10-year ASCVD risk from TG 150 to ≥500 mg/dL, ranged from 11.3% to 19.1% in statin users and 6.0% to 15.6% in nonusers, with an overall 3.4 million ASCVD events expected in the next 10 years.One-fourth of US adults overall, including nearly one-third of those on statin therapy, have suboptimal TG levels. More than 3 million ASCVD events are expected to occur over the next decade in those with TG ≥ 150 mg/dL, with approximately 1 million events expected in statin users.

There is currently limited information on the prognostic value of the dNLR-PNI (the combination of the derived neutrophil-to-lymphocyte ratio [dNLR] and prognostic nutritional index [PNI]) score for patients with acute coronary syndrome (ACS). We aimed to explore the predictive value of a dNLR-PNI score on the long-term prognosis of patients with ACS undergoing percutaneous coronary intervention (PCI). A total of 1773 patients with ACS who underwent PCI were consecutively enrolled from January 2016 to December 2018. The cutoff values of dNLR and PNI to predict major adverse cardiovascular events (MACE) were calculated using receiver operating characteristic curves. The patients were divided into three groups based on the dNLR-PNI score, and Kaplan–Meier curves and Cox regression models were used for survival analysis. The endpoints were MACE, including all-cause mortality and rehospitalisation for severe heart failure during follow-up. A total of 1542 patients with ACS who underwent PCI were included. Kaplan–Meier curves showed that a higher level of dNLR, PNI, or dNLR-PNI score was associated with a higher risk of MACE (all p < .001). In multivariate Cox regression models, the dNLR-PNI two score (hazard ratio 3.049, 95% confidence interval 1.503–6.184, p = .002) was found to be an independent predictor of all-cause mortality and rehospitalization for severe heart failure. A high dNLR-PNI score was independently associated with a higher risk of developing MACE in patients with ACS undergoing PCI. The dNLR-PNI score may be a useful prognostic parameter for identifying high-risk ACS patients after PCI.

Background: Atherosclerotic cardiovascular disease (ASCVD) risk prediction in persons with type 2 diabetes (T2DM) using existing calculators is imprecise. We aimed to develop a machine-learning (ML) model for prediction of ASCVD events in adults with T2DM. Methods: We utilized subjects with T2DM from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial without known CVD and calculated their 10-year ASCVD risk using the ACC/AHA pooled cohort risk calculator (PCRC) predicting the composite outcome of myocardial infarction, non-fatal stroke and cardiovascular death using age, gender, race, systolic blood pressure (SBP), antihypertensive medication use, total cholesterol, high-density lipoprotein cholesterol, current smoking status and diabetes mellitus status. We developed an ASCVD risk calculator based on Random Forest (RF) ML algorithms using follow-up data from ACCORD with the same 9 predictors. 5-fold stratified random split was applied as cross-validation strategies. Results: A total of 6581 T2DM participants without baseline ASCVD were included in our final sample with a median follow up of 9.1 years. The performance of PCRC was modest with an AUC=0.604. In contrast, the ML model had much better performance with a RF AUC=0.866. The figure shows the rank of feature importance (%) from random forest modeling (from high to low): age, systolic blood pressure, total cholesterol, HDL-C, female gender, White ethnicity, current smoker, hypertension treatment. Conclusion: The ML ASCVD Risk Calculator outperforms the AHA/ACC PCRC in predicting ASCVD outcomes among those with T2DM from the ACCORD trial. Age, SBP, total cholesterol and HDL-C were the most important features in ASCVD prediction among those with T2DM. Future studies need to validate these and other ML algorithms and to explore their applicability in guidelines.

Introduction: Coronary artery calcium (CAC) is a measure of subclinical atherosclerosis and predicts cardiovascular disease (CVD) events. Greater parity, or number of live births, has been shown to relate to CVD. We examined whether the relation of parity to CVD events may depend on the presence and extent of subclinical atherosclerosis measured by CAC. Methods: We studied 3151 women free of CVD at baseline in the Multi-Ethnic Study of Atherosclerosis, a prospective study of CVD. Participants were stratified by parity categories of 0-1 (reference), 2-3, and ≥4 and by baseline CAC categories of 0, 1-99, and 100+. We compared the incidence of CVD (myocardial infarction, stroke, resuscitated cardiac arrest, and coronary heart disease deaths) per 1000 years based on parity across levels of CAC over 13 years. Cox regression determined the joint association of parity and CAC on the incidence of CVD. Results: Women with greater parity had a higher prevalence of any CAC and CAC≥100 (pFigure ); however, from Cox regression analyses, these relations were attenuated when adjusted for age, ethnicity and other risk factors. Conclusion: In unadjusted analyses, we show parity to be associated with the prevalence of any or significant CAC, extent of CAC among those with CAC>0, as well as the incidence of CVD events, overall and according to the presence and extent of CAC. However, the association of parity with CVD risk was attenuated after adjustment for other factors.

Introduction: South Asians (SA) have increased atherosclerotic cardiovascular disease (ASCVD) risk and SA ethnicity is considered a “risk-enhancing factor” in the latest prevention guidelines. Diabetes mellitus (DM) is common in SA, but it is not known how pre-DM or DM may contribute to subclinical atherosclerosis in SA compared to other ethnic groups. We examined the association of pre-DM and DM to coronary artery calcium (CAC) in SA compared to 4 other ethnic groups. Methods: We studied data from SA, African Americans (AA), non-Hispanic whites (NHW), Chinese (CH), and Hispanics (HS) aged 45-84 without known ASCVD. SA were taken exclusively from MASALA and other groups from MESA. The prevalence of CAC 0, 1-99, 100-399, and 400+ were examined among those who were normoglycemic, pre-DM and DM. Multiple logistic regression adjusted for age, sex, smoking, cholesterol, and blood pressure identified the associations of pre-DM and DM (compared to normal glucose) on the odds of any CAC > 0 and significant CAC ≥ 100 by ethnicity. Results: Of the 7587 included individuals, mean age was 62±10 years, with 48% men, 10% SA, 25% AA, 34% NHW, 11% CH and 20% HS. The prevalence of pre-DM and DM varied significantly (p < 0.01) across ethnic groups: SA (25% and 21%), AA (15% and 18%), NHW (11% and 6%), CH (17% and 13%) and HS (15% and 17%). The prevalence of any CAC and CAC ≥ 100 in those with DM were highest in NHW (80% and 48%) and SA (72% and 41%). Pre-DM was only associated with CAC ≥ 100 in NHW (OR = 1.5, p < 0.01). Compared to other groups, SA with DM (compared to those normoglycemic) had the highest odds ratios (ORs) for CAC > 0 (OR = 3.35, p < 0.01) and CAC ≥ 100 (OR = 3.10, p < 0.01) (p = 0.01 and 0.07 for ethnicity interactions, respectively) (Table). Conclusions: Diabetes was associated with higher odds of any or significant CAC among SA compared to other ethnic groups. Ongoing longitudinal follow-up of the MASALA study cohort might help explain if DM contributes to the often premature ASCVD outcomes in SA.

Background: Individuals with no history of coronary artery disease can develop acute coronary syndrome (ACS), often in the absence of major risk factors including low-density lipoprotein cholesterol (LDL-C). We identified risk factors and biomarkers that can help identify those at discordantly high risk of ACS who have normal LDL-C using a novel coronary artery disease predictive algorithm (CADPA) incorporating biomarkers of endothelial injury validated in the Multi-Ethnic Study of Atherosclerosis cohort. Methods: Five-year predicted ACS risk was calculated using the CADPA for 8589 patients. Common risk factors and serum levels of 9 biomarkers utilized by the CADPA were tracked. We identified a “discordant high ACS” risk group with serum LDL-C < 130 mg/dL but 5-year CADPA predicted risk ≥ 7.5% and a “discordant low ACS” risk group defined as LDL-C ≥ 130 mg/dL but 5-year CADPA risk of < 7.5%. Multiple logistic regression identified risk factors and biomarkers that predicted discordance in two separate models. Results: The average age and percent male of the high ACS discordant group was higher compared to non-discordant (68±10 vs 54±13 years and 61% vs 43%, respectively). Diabetes (OR 2.84 [2.21-3.66]), male sex (OR 2.83 [2.40-3.35]), family history (OR 2.23 [1.88-2.64]) and active smoking (OR 1.99 [1.50-2.62]) exhibited greatest odds of high ACS discordance compared to other risk factors (all p < 0.01). Increased serum soluble FAS (OR 2.12 [1.97-2.29]), Hemoglobin A1c (OR 1.60 [1.48-1.72]) and interleukin-16 (OR 1.40 [1.32-1.48]) were the biomarkers most associated with discordant risk, independent of global risk factors. Conclusion: Men with diabetes and family history of myocardial infarction who are actively smoking may be at highest risk of developing ACS despite controlled LDL-C. Future studies should examine whether using the CADPA can help identify such individuals that could benefit from earlier targeting of risk factor modification for prevention of ACS.

Background: Liver fibrosis is a complication of non-alcoholic fatty liver disease (NAFLD) and is associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. Whether this risk may be enhanced in persons with pre-diabetes (pre-DM) or diabetes (DM), however, is not established. We examined the association of liver fibrosis with estimated ASCVD risk and its predictors according to DM status. Methods: We studied 30,895 adults (3,983 or 12.9% with DM) from the National Health and Nutrition Examination Surveys 1999-2014 with liver function measures to calculate FIB-4 scores; values of 1.3-2.67 and >2.67 indicated a moderate and high probability of advanced fibrosis, respectively. We studied the prevalence high FIB-4 scores in those with and without pre-DM and DM and the 10-year ASCVD risk based on the ACC/AHA Pooled Cohort Risk Calculator in persons without known ASCVD. In addition, multiple logistic regression examined predictors of high FIB-4 scores. Results: The prevalence of FIB-4 scores of 1.3-2.67 and >2.67 ranged from 17.8% and 1.5% in those without pre-DM/DM, 29.9% and 2.5% in those with pre-DM, and 35.3% and 3.5% in those with DM, respectively (p2,67 were age (odds ratio [OR]=3.0 / 10 years), female sex (OR=0.53), non-Hispanic Black ethnicity (OR=2.0), waist circumference (OR=0.76/SD), alcohol use (OR=1.5), and NALFD (OR=3.3) in those without DM, and age (OR=2.2/10 years), female sex (OR=0.48), systolic blood pressure (1.4/SD), diastolic blood pressure (0.76/SD), and current smoking (OR=2.2) in those with DM (all p Conclusions: Advanced fibrosis is more prevalent in those with vs. without DM. The presence of DM with higher FIB-4 scores is associated with especially high estimated ASCVD risks warranting increased efforts to address prevention and treatment of liver fibrosis.

Aim: We examined eligibility and preventable cardiovascular disease events in US adults with diabetes mellitus from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME). Methods: We identified adults with diabetes mellitus eligible for EMPA-REG OUTCOME based on trial eligibility criteria available from the National Health and Nutrition Examination Surveys, 2007–2016. We estimated composite cardiovascular disease endpoints, as well as all-cause deaths, death from cardiovascular disease and hospitalizations for heart failure from trial treatment and placebo event rates, the difference indicating the preventable events. Results: Among 29,629 US adults aged ⩾18 years (representing 231.9 million), 4672 (27.3 million) had diabetes mellitus, with 342 (1.86 million) meeting eligibility criteria of EMPA-REG OUTCOME. We estimated from trial primary endpoint event rates of 10.5% and 12.1% in the empagliflozin and placebo groups, respectively, that based on the ‘treatment’ of our 1.86 million estimated EMPA-REG OUTCOME eligible subjects, 12,066 (95% confidence interval: 10,352–13,780) cardiovascular disease events could be prevented annually. Estimated annual preventable deaths from any cause, cardiovascular causes and hospitalizations from heart failure were 17,078 (95% confidence interval: 14,652–19,504), 14,479 (95% confidence interval: 12,422–16,536) and 9467 (95% confidence interval: 8122–10,812), respectively. Conclusion: Empagliflozin, if provided to EMPA-REG OUTCOME eligible US adults, may prevent many cardiovascular disease events, cardiovascular and total deaths, as well as heart failure hospitalizations.

The reduction of cardiovascular events with icosapent ethyl-intervention (REDUCE-IT) trial showed in persons with prior cardiovascular disease (CVD) or diabetes mellitus (DM) that icosapent ethyl (IPE) reduced CVD events by 25%. We projected the preventable initial and total CVD events if REDUCE-IT trial eligibility criteria were applied to US adults. We identified US adults with available REDUCE-IT inclusion criteria from NHANES Surveys 1999-2016 and estimated primary (CVD death, nonfatal myocardial infarction, stroke, revascularization, or unstable angina) and secondary composite (CVD death, nonfatal MI or stroke) events using REDUCE-IT published event rates in the IPE and placebo groups, the difference being the number of preventable events. From 11,445 adults aged ≥45 years (representing 111.1 million [M]), a total of 319 persons (3.0 M) fit key REDUCE-IT eligibility criteria: triglycerides of 135 to 499 mg/dL, HbA1c10%, blood pressure200/100 mm Hg, and on a statin with LDL-C of 40 to 99 mg/dL. 63% had prior CVD and 37% had DM + ≥1 risk factor (primary prevention cohort). If these persons are given IPE for the REDUCE-IT median trial period of 4.9 years, we estimated preventing a total 349,817 (71,391/year) primary CVD outcomes of which 146,011 (29,798/year) were initial events. Most (24,151) preventable events were from the secondary prevention cohort. Using FDA eligibility criteria, an estimated 4.6 million persons would be eligible for IPE, with 60,544 preventable primary CVD outcomes annually from REDUCE-IT USA event rates. In conclusion, many CVD events in US adults with known CVD or DM and well-controlled LDL-C on statin therapy can be prevented with IPE.

The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial showed the cardiovascular disease (CVD) benefits of liraglutide therapy among patients with type 2 diabetes mellitus (T2DM). We applied this trial to US adults with T2DM in terms of eligibility and preventable CVD events. We included US adults with T2DM from the National Health and Nutrition Examination Survey (NHANES) 2007–2016. Eligibility criteria from LEADER primary and secondary prevention cohorts were applied to determine potentially eligible US adults. We estimated the number of primary composite and secondary CVD endpoints that would occur based on LEADER treated and placebo published event rates, with the difference indicating the number of preventable events. Among 4672 (projected to 27.3 million [M]) adults we identified with T2DM, we estimated 800 (4.2 million) (15.4%) to fit LEADER eligibility criteria, including 205 (0.9 M) primary prevention 595 (3.3 M) secondary prevention subjects. Compared to LEADER trial participants, our sample had higher proportions of women and minorities, prior angina, chronic kidney disease, and lipid-lowering medication use. We estimated 21,209 primary composite CVD events, 29,691 extended CVD composite outcomes, 16,967 all-cause deaths, 16,967 cardiovascular deaths, 12,725 myocardial infarctions, and 12,725 microvascular events would be prevented annually if our eligible T2DM subjects were on liraglutide. Liraglutide may prevent many fatal and non-fatal CVD events if provided to US adults meeting LEADER eligibility criteria. More efforts are needed to educate the healthcare providers on the CVD benefits from newer diabetes therapies, including liraglutide.

Purpose of Review In recent years, a family of adiponectin paralogs designated as C1q/TNF-related protein (CTRP) has attracted increasing attention. They are inflammatory adipocytokines mostly secreted from epicardial adipose tissue, which modulate the development and prognosis of coronary artery disease (CAD). This review summarizes the pathophysiological roles of individual members of the CTRP superfamily in the development of CAD. Recent Findings Recent studies have revealed how members of the CTRP family, CTRP1, CTRP3, CTRP5, CTRP9, CTRP12, and CTRP13, can influence both development and progression of CAD by modulating metabolic pathways, influencing immuno-inflammatory response, and regulating cardiovascular functions. Summary Research to date has not been sufficient to answer the specific mechanism of the CTRP family in the occurrence and development of CAD. This review explores the evidence of CTRP superfamily regulating different pathophysiology stages of CAD through the immuno-inflammation, glucose and lipid metabolism, and vascular endothelial function.

Background: The AHA/ACC published a pooled cohort 10-year atherosclerotic cardiovascular disease (ASCVD) risk calculator to estimate the probability of initial ASCVD events based on statistical modeling. Our current study aimed to develop machine-learning models with the identical predictors among T2DM patients from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and further compared their performance in predicting composite outcome of myocardial infarction, non-fatal stroke and cardiovascular death. Methods: The guideline risk calculator provided 9 predictors including baseline age, gender, race, SBP, antihypertensive medication use, total cholesterol, high-density lipoprotein cholesterol, current smoking status and diabetes mellitus status. We developed three ML ASCVD Risk Calculators based on Linear Model (LM), Supporting Vector Machine (SVM) and Random Forest (RF) algorithms using 10-year follow-up data from ACCORD with the same 9 predictors. T2DM patients with prior ASCVD or with invalid follow-up time were excluded in our analysis. Those who had not experienced the composite outcome by the end of year 10 would be labeled as censored. 5-fold stratified random split was applied as a cross-validation strategy. Results: A total of 6581 T2DM participants were included in our final sample, with a mean age of 62.9±5.9 years old (range 51-79 yr), 44.1% female and 60.8% white. Among those, 12.2% (n=802) had developed composite ASCVD during a median follow up of 9.1 years. The performance AHA/ACC 10-year Risk Calculator was modest with AUC=0.604. In contrast, ML models showed better performance from validation data with LM AUC=0.854, SVM AUC=0.848, and RF AUC=0.866 (Figure). Conclusion: The ML ASCVD Risk Calculator outperforms the AHA/ACC pooled 10-year ASCVD risk calculator in predicting the composite ASCVD outcomes among those with DM from ACCORD trial. Future studies need to validate ML algorithms in other cohorts and further explore other potential valuable predictors.

n/a - brief communication.

Diabetes mellitus (DM) has become a rising epidemic in the last century, more pressing in the last few decades with the exponential rise of obesity, and has become one of the leading causes of death worldwide. Genetic variants have also been a new field of epidemiology research to determine the underlying genetic component of those risk factors and the association of DM with CVD. In light of its significant prevalence, patients remain unaware of their disease progression that arises from genetic and metabolic risk factors. As compared to non-diabetics, those with type 2 DM carry a higher mortality risk from cardiovascular disease (CVD) across different ethnicity groups and sex. The most common cardiovascular manifestations in those with DM include heart failure, peripheral arterial disease, and coronary heart disease. Although DM does predispose patients to CVD, it in fact is not a risk equivalent, but carries significant heterogeneity in risk for CVD.

Lipoprotein(a) (Lp(a)) is a genetically determined LDL particle with proatherogenic and prothrombotic properties. The long-term impact of increased Lp(a) on cardiovascular disease (CVD) and all-cause mortality in patientswith diabetes mellitus (DM) is not known. We examined the association of Lp(a

The REDUCE-IT trial showed in persons with prior cardiovascular disease (CVD) or diabetes mellitus (DM) that icosapent ethyl in reduced CVD events by 25%. We projected the preventable initial and total CVD events if REDUCE-IT trial eligibility criteria were applied to US adults. We identified US

Background and aims Certain novel biomarkers may predict atherosclerotic cardiovascular disease (ASCVD) events; however, data on their relationship to coronary atherosclerosis and its progression as measured by coronary artery calcium (CAC) scanning is lacking. We evaluated the association between novel biomarkers and presence or progression of CAC. Methods The EISNER study was a prospective trial of patients without known ASCVD. Data on CAC and several biomarkers (hs-CRP, LTβR, osteopontin [OPN], RAGE, TNFR1α and TROY) were available at baseline and 4-year follow-up. Biomarkers were standardized and summed for a composite score. CAC progression was defined by the square-root (CACSQRT) method and rapid (top decile) progression. Adjusted regression models created a final prediction model for baseline CAC and CAC progression. Results 1207 subjects (mean age 58.4 ± 8 years, 53% male) were evaluated; 621 had a baseline CAC >0, in whom 323 progressed by CACSQRT, and 121 rapidly progressed. Baseline CAC was associated only with OPN (p = 0.03), TROY (p = 0.0058) and TNFR1α (p = 0.0039) in unadjusted analyses. In adjusted analyses, only OPN was independently related to CAC progression using CACSQRT (p = 0.04). Conclusions OPN identifies progression of atherosclerosis in persons free of ASCVD at baseline and may be a useful predictive tool to guide ASCVD prevention management.

Traditional global risk assessment for cardiovascular disease fails to identify a significant percentage of the population initially classified at low or intermediate risk of cardiovascular disease that are actually at high risk for acute coronary syndrome (ACS). We examined a coronary artery disease predictive algorithm (CADPA) that includes 9 biomarkers involved in the pathogenesis of atherosclerosis initiated by endothelial damage and repair (hepatocyte growth factor, soluble FAS, Fas ligand, eotaxin, cutaneous T cell-attracting chemokine, monocyte chemotactic protein-3, interleukin-16, hemoglobin A1c, high-density lipoprotein-cholesterol), in addition to age, gender, diabetes, and family history of myocardial infarction that more accurately predicts 5-year risk of ACS to identify the patient population at discordantly high risk. We found that 34% of patients at low risk by global risk assessment and 72% of patients at intermediate risk by global risk assessment were actually at discordantly high risk for ACS. This patient population was disproportionately male and older in age. The biomarkers (per standard deviation) that most predicted the odds (95% confidence levels) of discordance were interleukin-16 (2.59 [2.21 to 3.03]), Fas Ligand (0.50 [0.43 to 0.57]), hepatocyte growth factor (1.72 [1.50 to 1.98]), soluble FAS (2.19 [1.86 to 2.58]), cutaneous T cell-attracting chemokine (0.46 [0.40 to 0.53]), and eotaxin (1.78 [1.56 to 2.03]), in addition to age, HbA1c, low-density lipoprotein-cholesterol, and glycated hemoglobin. In conclusion, although future prospective study validation is needed to establish a causal relation between CADPA and cardiovascular events, our study defines a patient population considered low to intermediate risk by conventional clinical evaluation, but who is at discordantly high risk indicated by the endothelial injury serum biomarker algorithm CADPA and may benefit from further evaluation and medical management.

To explore the effect of comprehensive rehabilitation training (CRT) on cognitive impairment, anxiety, and depression in poststroke patients.168 poststroke patients were consecutively recruited in this randomized controlled study. Patients were randomly assigned to CRT group (CRT plus conventional treatment) and control group (conventional treatment) as 1:1 ratio. The specific interventions of CRT included patient and family member education, cognitive training, rehabilitation training, and regular check.Both montreal cognitive assessment score change (Month12 [M12]-baseline; P = .001) and minimum mental state examination score change (M12-baseline) were higher in CRT group than that in control group (P = .004), and the percentage of cognitive impairment by montreal cognitive assessment score ≤26 was lower (P = .003) in CRT group compared to control group at month 12. Anxiety assessments were performed by hospital anxiety and depression scale (HADS) and Zung self-rating anxiety scale (SAS). The HADS anxiety score change (M12-baseline; P = .002) and the SAS score change (M12-baseline; P = .006) were decreased in CRT group compared to control group. Lower occurrence rate of anxiety assessed by SAS was observed in CRT group compared to control group (P = .033). Depression assessments were performed by HADS and Zung self-rating depression scale (SDS). HADS depression score change (M12-baseline; P.001) and the SDS score change (M12-baseline; P = .002) were reduced in CRT group compared to control group. Decreased occurrence rate of depression assessed by SDS was found in CRT group compared to control group (P = .022).CRT contributes to the recovery of cognitive impairment, and decreases anxiety and depression in poststroke patients.

Background: Patients with diabetes mellitus (DM) are at increased risk of acute coronary syndrome (ACS); however, the factors predicting those at highest risk are not well-understood. We identified demographic and standard risk factors that best predict those at high risk based on a multiple biomarker algorithm. Methods: We studied adults with DM from a clinical registry who had measures of the PULS score (GD Biosciences, Irvine, CA), a biomarker algorithm identifying endothelial damage and predicting 5-year ACS risk consisting of HGF, sFAS, Fas Ligand, Eotaxin, CTACK, MCP3, Il-16, HbA1c, HDL-C, as well as age, sex, DM, and family history of CHD. We identified the proportion of patients with DM at low ( Results: There were 668 adults with DM (females: 39.5%, ages 30 to 100, mean age 66.5 years). Of these, 6.0% had a low, 12.9% intermediate, and 81.1% high risk PULS score. In the stepwise logistic regression, independent predictors of a high risk PULS score included age, sex, hypertension, body mass index (BMI), and current smoking (table). Other risk factors and biomarkers, including apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB), ratio ApoB to ApoA1, total or LDL-cholesterol, triglycerides, very low density lipoprotein cholesterol, lipoprotein (a), systolic or diastolic blood pressure, hs-CRP, and small dense LDL were not associated with a high PULS risk score. Conclusion: We demonstrated that age, male gender, hypertension, BMI, and current smoking are key factors potentially identifying persons with DM at high risk of ACS based on an algorithm identifying endothelial damage. Further validation through prospective studies with actual ACS events are needed.

Background & Objectives: The role of lipid and lipoprotein biomarkers in risk prediction of ischemic heart disease is well established, but their value as independent predictors for ischemic stroke is less certain. Certain LDL subclasses based on particle sizes are associated with atherosclerotic risk. However, there is little information available on the relation of LDL particle number (LDL-P, nmol/L), LDL particle size (nm) with stroke. We evaluated associations between LDL-P and LDL particle size with the risk of ischemic stroke (IS) and transient ischemic attack (TIA). Methods: We studied US adults aged of 45-84 years not on lipid-lowering medications enrolled in the Multi-Ethnic Study of Atherosclerosis between 2000 and 2002 with follow-up through December 2011. We evaluated associations of LDL-P (total LDL-P, large LDL-P and small LDL-P) and LDL particle size measured by NMR with, (1) composite of incident IS and TIA, and (2) IS alone. Standardized hazard ratios (HRs) were adjusted for age, sex, race (model 1), plus diabetes, hypertension medication, systolic and diastolic blood pressure, family history, smoking, HDL (model 2), and plus LDL concentration (model 3). Results: We identified 129 subjects with incident IS, 61 with TIA and 5,328 without any type of stroke during follow-up; mean ages were 67.4, 66.7 and 61.2 years, respectively (p Conclusions: Increased small LDL-P, not particle size, is most closely associated with incident IS and could be useful in risk stratification beyond standard risk factors and lipid measures.

Diabetes mellitus and angina pectoris are important conditions in older persons. The utility of pre-diabetes mellitus, diabetes mellitus and other risk factors as predictors of incident angina pectoris among older adults has not been characterized. We examined incident angina pectoris rates by sex and diabetes mellitus status in 4511 adults aged ⩾65 years without coronary heart disease at baseline from the Cardiovascular Health Study. Cox regression examined predictors of incident angina pectoris, including pre-diabetes mellitus or diabetes mellitus adjusted for sociodemographic characteristics and other risk factors, over 12.2 ± 6.9 years of follow-up. Overall, 39.1% of participants had pre-diabetes mellitus, 14.0% had diabetes mellitus and 532 (11.8%) had incident angina pectoris. Incident angina pectoris rates per 1000 person-years in those with neither condition, pre-diabetes mellitus, and diabetes mellitus were 7.9, 9.0 and 12.3 in women and 10.3, 11.2 and 14.5 in men, respectively. Pre-diabetes mellitus and diabetes mellitus were not independently associated with incident AP; however, key predictors of AP were male sex, low-density lipoprotein-cholesterol, triglycerides, systolic blood pressure, antihypertensive medication and difficulty performing at least one instrumental activity of daily living (all p

The EMPA-REG OUTCOME trial recently demonstrated in persons with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD) the efficacy of empagliflozin in reducing CVD events, as well as heart failure hospitalizations, cardiac and total mortality. The potential impact of EMPA-REG

Prior studies have demonstrated that the prevalence of isolated systolic hypertension (ISH) increases with age. We examined whether the presence of diabetes mellitus (DM) relates to an earlier increased prevalence of ISH. We studied adults with untreated hypertension (HTN), defined as a systolic

Persons with hypertriglyceridemia (HTG) have greater risks for atherosclerotic cardiovascular disease (ASCVD), and statin therapy is indicated as initial treatment. Our aim was to estimate ASCVD risk and events for persons with and without HTG, according to statin use. We studied 4,986 adults (

As one of the leading causes of death in the USA, diabetes mellitus (DM) has become an epidemic over the past few decades. Despite the high prevalence of diagnosed DM, close to half of all people with DM are unaware of their disease. The risk of type 2 DM is determined by interplay of genetic and metabolic factors. Patients with type 2 DM have a higher risk of death from cardiovascular causes compared with their nondiabetic counterparts, and the mortality rate of DM associated cardiovascular disease is different among ethnicity groups and sex groups. Because of its adverse effect on people's health, DM also imposes an economic burden on individuals and households affected, as well as on the healthcare system. Current guidelines for cardiovascular disease prevention have focused on lifestyle management, blood pressure control, lipid control, blood glucose control, antiplatelet agent use, and tobacco use cessation.

Certain novel biomarkers may predict atherosclerotic cardiovascular disease (ASCVD) events; however, data on their relationship to coronary atherosclerosis and its progression as measured by coronary artery calcium (CAC) scanning is lacking. We evaluated the association between novel biomarkers and

BACKGROUND: Though it is a widely held belief that caffeinated beverages predispose individuals to arrhythmias, it is not clear whether regular coffee consumption is associated with development of atrial fibrillation (AF). OBJECTIVE: We examined the association between long-term coffee consumption and development of AF in both habitual (≥0.5 cups of daily coffee) and nonhabitual (0 to 0 to 0.5 cups of daily coffee) was associated with a greater risk of incident AF (HR 1.22, 95% CI 1.01-1.48) relative to 0 cups/day in multivariable Cox proportional hazards models after adjustment for numerous AF risk factors. This relation was particularly pronounced in men (adjusted HR=1.36, 95% CI 1.04-1.77). Higher coffee consumption was not associated with AF risk (HR 1.03, 95%CI 0.93-1.14 for ≥0.5 to 1.5 cups/day and 1.05, 95%CI 0.97-1.13 for ≥1.5 cups/day). CONCLUSIONS: While there appears to be no dose-response association between habitual coffee intake and AF risk, we found evidence that intermittent, but not habitual, coffee consumption is associated with a modestly increased risk of incident AF that deserves further study.