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The rationale of this study was to examine the effectiveness of 6-month high-impact step aerobics (SA) or moderate-intensity resistance training exercise (RT) on bone mineral density (BMD) and bone bending strength in sedentary women. Results show that SA enhanced BMD in the heel, lower leg, and lumbar spine 2. To determine the effectiveness of 6 months of high-impact step aerobics (SA) or moderate-intensity resistance training (RT) on areal bone mineral density (aBMD) and tibial bending strength in sedentary premenopausal women. Sixty-nine women (20–35 years old) who were randomly assigned to RT (n = 22), SA (n = 26), or non-treatment control (CON, n = 21) groups completed the study. SA had a minimum of 50 high-impact landings each training session. RT had a periodized lower body resistance training program incorporating eight exercises (65–85% of 1 repetition maximum: 1-RM). Both RT and SA met 3 times weekly. aBMD was assessed using dual X-ray absorptiometry (DXA). Tibial bending strength was assessed using mechanical response tissue analysis (MRTA). Measurements at 6 months were compared to baseline using ANCOVA, adjusted for baseline measures and covariates with α = 0.05. Calcaneus aBMD (0.0176 vs -0.0019 or -0.0009 g/cm2 relative to RT, p

OBJECTIVE We examined diabetes as a cardiovascular disease (CVD) risk equivalent based on diabetes severity and other CVD risk factors. RESEARCH DESIGN AND METHODS We pooled four U.S. cohorts (Atherosclerosis Risk in Communities [ARIC], Jackson Heart Study [JHS], Multi-Ethnic Study of Atherosclerosis [MESA], and Framingham Heart Study Offspring Cohort [FHS-Offspring]) and classified subjects into groups by baseline diabetes/CVD status (positive or negative). CVD risks of the diabetes mellitus (DM)+/CVD− group versus DM−/CVD+ group were examined by diabetes severity and in subgroups of other CVD risk factors. We developed an algorithm to identify subjects with CVD risk equivalent diabetes by comparing the relative CVD risk of being DM+/CVD− versus DM−/CVD+. RESULTS The pooled cohort included 27,730 subjects (mean age 58.5 years, 44.6% male). CVD rates per 1,000 person-years were 16.5, 33.4, 43.2, and 71.4 among those DM−/CVD−, DM+/CVD−, DM−/CVD+, and DM+/CVD+, respectively. Compared with those DM−/CVD+, CVD risks were similar or higher for those with HbA1c ≥ 7%, diabetes duration ≥10 years, or diabetes medication use, while those with less severe diabetes had lower risks. Hazard ratios (95% CI) for DM+/CVD− vs. DM−/CVD+ were 0.96 (95% CI 0.86–1.07), 0.97 (0.88–1.07), 0.96 (0.82–1.13), 1.18 (0.98–1.41), 0.93 (0.85–1.02), and 1.00 (0.89–1.13) among women and those of White race, age CONCLUSIONS Diabetes is a CVD risk equivalent in one-fifth of CVD-free adults living with diabetes. High HbA1c, long diabetes duration, and diabetes medication use were predictors of CVD risk equivalence. Diabetes is a CVD risk equivalent for women, white people, and those of younger age or with higher triglycerides or hs-CRP or reduced kidney function.

Aims We examined cardiovascular outcomes associated with initiation of glucagon-like peptide-1 receptor agonist (GLP-1RA) vs. sodium–glucose co-transporter-2 inhibitor (SGLT-2i) treatment in a real-world setting among patients with type 2 diabetes. Methods and results This Danish nationwide registry-based cohort study included patients with type 2 diabetes with a first-ever prescription of either GLP-1RA or SGLT-2i from 2013 through 2015 with follow-up until end of 2018. All analyses were standardized with respect to age, sex, diabetes duration, comorbidity, and comedication. The main outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Furthermore, the components of the composite outcome and hospitalization for heart failure were evaluated. Standardized average 3-year risks of outcomes and differences thereof were estimated using doubly robust estimation combining cause-specific Cox regression with propensity score regression. We identified 8913 new users of GLP-1RA and 5275 new users of SGLT-2i. The standardized 3-year risk associated with initiating GLP-1RA and SGLT-2i, respectively, was as follows: composite cardiovascular outcome, 5.6% [95% confidence interval (CI): 5.2–6.1] vs. 5.6% (95% CI: 4.8–6.3); cardiovascular mortality, 1.6% (95% CI: 1.3–1.9) vs. 1.5% (95% CI: 1.1–1.8); hospitalization for heart failure, 1.7% (95% CI: 1.5–2.0) vs. 1.8% (95% CI: 1.2–2.5); myocardial infarction, 2.1% (95% CI: 1.8–2.4) vs. 2.1% (95% CI: 1.5–2.6); and stroke, 2.5% (95% CI: 2.2–2.9) vs. 2.6% (95% CI: 2.2–3.1). Conclusion In this nationwide study of patients with type 2 diabetes, initiating GLP-1RA vs. SGLT-2i was not found to be associated with significant differences in cardiovascular risk.

Current risk stratification strategies do not fully explain cardiovascular disease (CVD) risk. We aimed to evaluate the association of low-density lipoprotein (LDL-P) and high-density lipoprotein (HDL-P) particles with progression of coronary artery calcium and carotid wall injury. All participants in the Multi-Ethnic Study Atherosclerosis (MESA) with LDL-P and HDL-P measured by ion mobility, coronary artery calcium score (CAC), carotid intima-media thickness (IMT), and carotid plaque data available at Exam 1 and 5 were included in the study. CAC progression was annualized and treated as a categorical or continuous variable. Carotid IMT and plaque progression were treated as continuous variables. Fully adjusted regression models included established CVD risk factors, as well as traditional lipids. Mean (±SD) follow-up duration was 9.6 ± 0.6 years. All LDL-P subclasses as well as large HDL-P at baseline were positively and significantly associated with annualized CAC progression, however, after adjustment for established risk factors and traditional lipids, only the association with medium and very small LDL-P remained significant (β -0.02, p = 0.019 and β 0.01, p = 0.003, per 1 nmol/l increase, respectively). Carotid plaque score progression was positively associated with small and very small LDL-P (p

Background and aimsWe sought to assess the performance of a comprehensive machine learning (ML) risk score integrating circulating biomarkers and computed tomography (CT) measures for the long-term prediction of hard cardiac events in asymptomatic subjects.MethodsWe studied 1069 subjects (age 58.2±8.2 years, 54.0% males) from the prospective EISNER trial who underwent coronary artery calcium (CAC) scoring CT, serum biomarker assessment, and long-term follow-up. Epicardial adipose tissue (EAT) was quantified from CT using fully automated deep learning software. Forty-eight serum biomarkers, both established and novel, were assayed. An ML algorithm (XGBoost) was trained using clinical risk factors, CT measures (CAC score, number of coronary lesions, aortic valve calcium score, EAT volume and attenuation), and circulating biomarkers, and validated using repeated 10-fold cross validation.ResultsAt 14.5±2.0 years, there were 50 hard cardiac events (myocardial infarction or cardiac death). The ML risk score (area under the receiver operator characteristic curve [AUC] 0.81) outperformed the CAC score (0.75) and ASCVD risk score (0.74; both p=0.02) for the prediction of hard cardiac events. Serum biomarkers provided incremental prognostic value beyond clinical data and CT measures in the ML model (net reclassification index 0.53 [95% CI: 0.23-0.81], p&nbsp

Objectives The purpose of this study was to identify predictors of healthy arterial aging (long-term coronary artery calcification [CAC] of 0) among individuals with metabolic syndrome (Me...

The rapidly expanding field of preventive cardiology has brought with it several major advances in the past decade. Changes in guidelines for cholesterol mangement focusing on the identification of "statin eligible groups" and removal of actual low-density lipoprotein cholesterol (LDL-C) targets, in particular, as well as lower targets for blood pressure in updated hypertension guidelines, have made a major impact on healthcare. The availability of the sodium glucose transport protein-2 (SGLT2) inhibitors and glucagon-like peptide -1 receptor antagonists (GLP1-RA) for managing diabetes have shifted our focus in diabetes care beyond glucose lowering to addressing cardiovascular risk reduction. While many prior trials of fish oil therapy have failed to show benefit, the recent Reduction of Cardiovascular Events With EPA - Intervention Trial (REDUCE-IT) testing the efficacy of icosapent ethyl has shown dramatic benefit in further addressing residual atherosclerotic cardiovascular disease (ASCVD) risk beyond statin therapy not only in those with known ASCVD, but also in diabetic patients with multiple risk factors. The past decade also ushered in confirmation of the inflammation hypothesis of atherosclerosis with the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) using canakinumab, despite the fact the therapy was not approved by the Food and Drug Administration (FDA) for cardiovascular risk reduction. Also, to improve our understanding of heart disease in women, the emergence of novel concepts of ischemia or myocardial infarction in those with normal or nonobstructive atherosclerotic disease has been a major advance. Moreover, the past decade brought the emergence of proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody therapy and the cardiovascular risk reduction benefits seen in the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) and Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab (ODYSSEY OUTCOMES) trials, providing further evidence-based therapy for additional reduction of ASCVD risk beyond statin therapy. The PCSK9 monoclonal antibodies have facilitated the attainment of LDL-C levels never previously thought possible. Finally with the mRNA interference therapy inclisiran in development, we may soon have a "vaccine-like" approach for addressing dyslipidemia and atherosclerosis.

International guidelines suggest revascularization within 24 hours in non-ST segment elevation myocardial infarction (NSTEMI). Within a large population cohort study, we aimed to explore clinical practice regarding timing targets for percutaneous coronary intervention (PCI) in NSTEMI. The Victorian Cardiac Outcomes Registry was established in 2013 as a state-wide clinical quality registry, pooling data from public and private PCI capable centers. Data were collected on 11,852 PCIs performed for NSTEMI from 2014 to 2018. Patients were divided into 3 groups by time of symptom onset to PCI (24 hours; 24 to 72 hours;72 hours). We performed multivariable logistic regression analysis conditional on several baseline covariates in investigating the impact of timing of PCI in NSTEMI on clinical outcomes. Patients who underwent PCI within 24 hours represented 18.4% (n = 2,178); 24 to 72 hours 45.8% (n = 5,434);72 hours 35.8% (n = 4,240). Patients waiting longer for PCI were older (62.6 ± 12.2 vs 64.8 ± 12.6 vs 67.0 ± 12.7, p0.001), more likely to be female (23.1% vs 24.2% vs 26.4%, p = 0.007), and have diabetes (18.6% vs 21.1% vs 27.1%, p0.001). Multivariate logistic regression found that as compared with PCI24 hours, PCI 24 to 72 hours and PCI72 hours of symptom onset were associated with a decreased risk of 30-day mortality (odds ratio 0.55; 95% confidence interval 0.35 to 0.86, p = 0.008 and odds ratio 0.64; 95% confidence interval 0.35 to 1.01, p = 0.053, respectively). There was no significant difference in 30-day mortality between groups following exclusion of patients presenting with cardiogenic shock or out of hospital cardiac arrest requiring intubation. In conclusion, many registry patients undergo PCI outside the 24-hour window following NSTEMI. This delay is at odds with current guideline recommendations but does not appear to be associated with an increased mortality risk.

Author(s): Cordola Hsu, Amber R; Ames, Susan L; Xie, Bin; Peterson, Darleen V; Garcia, Lorena; Going, Scott B; Wong, Nathan D; Anton-Culver, Hoda | Abstract: To identify sociodemographic and metabolic correlates of weight categories in postmenopausal women.MethodsThe Women's Health Initiative enrolled 161 808 postmenopausal women ages 50-79. We included those free of cardiovascular disease (CVD) and with CVD risk factors and biomarkers (n = 19 412). Normal weight was defined as a BMI ≥18.5 and l25 kg/m2 and waist circumference l88 cm and overweight/obesity as a BMI ≥25 kg/m2 or waist circumference ≥88 cm. Metabolically healthy was based on l2 and metabolically unhealthy ≥2 traits: triglycerides ≥150 mg/dl, systolic blood pressure (BP) ≥130 mmHg or diastolic BP ≥85 mmHg or antihypertensives or diuretics, fasting glucose ≥100 mg/dl or diabetes medication, and high-density lipoprotein cholesterol l50 mg/dl. Polytomous multinomial logistic regression with generalized link logit function provided the odds of metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUHNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUHO) according to demographic and risk factor measures.ResultsAmong the 19 412 postmenopausal women, 2369 (12.2%) participants had prevalent diabetes. Advanced age was associated with an increased odds of MUHNW as compared with the MHNW after adjusting for covariates [odds ratio (OR) 1.04, P l 0.0001]. Black/African American ethnicity was associated with a decreased odds of MUHNW (OR 0.64, P l 0.0001) and MUHO (OR 0.77, P = 0.0004), while an increased odds for MHO (OR 1.50, P l 0.0001) as compared with White MHNW.ConclusionsAdvanced age and ethnicity are important indicators of metabolic weight categories among postmenopausal women.

Heterochronic blood sharing rejuvenates old tissues, and most of the studies on how this works focus on young plasma, its fractions, and a few youthful systemic candidates. However, it was not formally established that young blood is necessary for this multi-tissue rejuvenation. Here, using our recently developed small animal blood exchange process, we replaced half of the plasma in mice with saline containing 5% albumin (terming it a "neutral" age blood exchange, NBE) thus diluting the plasma factors and replenishing the albumin that would be diminished if only saline was used. Our data demonstrate that a single NBE suffices to meet or exceed the rejuvenative effects of enhancing muscle repair, reducing liver adiposity and fibrosis, and increasing hippocampal neurogenesis in old mice, all the key outcomes seen after blood heterochronicity. Comparative proteomic analysis on serum from NBE, and from a similar human clinical procedure of therapeutic plasma exchange (TPE), revealed a molecular re-setting of the systemic signaling milieu, interestingly, elevating the levels of some proteins, which broadly coordinate tissue maintenance and repair and promote immune responses. Moreover, a single TPE yielded functional blood rejuvenation, abrogating the typical old serum inhibition of progenitor cell proliferation. Ectopically added albumin does not seem to be the sole determinant of such rejuvenation, and levels of albumin do not decrease with age nor are increased by NBE/TPE. A model of action (supported by a large body of published data) is that significant dilution of autoregulatory proteins that crosstalk to multiple signaling pathways (with their own feedback loops) would, through changes in gene expression, have long-lasting molecular and functional effects that are consistent with our observations. This work improves our understanding of the systemic paradigms of multi-tissue rejuvenation and suggest a novel and immediate use of the FDA approved TPE for improving the health and resilience of older people.

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

OBJECTIVE To determine the relationship of metabolic weight categories with incident diabetes mellitus (DM) in postmenopausal women. METHODS The Women's Health Initiative (WHI) enrolled 161,808 postmenopausal women aged 50 to 79 years. We included those with cardiovascular disease (CVD) biomarkers and free of CVD and prevalent DM (n = 17,043) at baseline. Normal weight was defined as a body mass index (BMI) ≥18.5 and

INTRODUCTION AND OBJECTIVE:Rezūm is a minimally invasive treatment for benign prostatic hyperplasia (BPH) that uses injections of sterile water vapor directly into the prostate for ablation. Althou...

INTRODUCTION AND OBJECTIVE:While lower tract urothelial carcinoma has undergone multiple large gene expression profiling initiatives, upper tract urothelial carcinoma (UTUC) has had relatively litt...

Stroke is the second most common cause of death worldwide. The rates of stroke are increasing in less affluent countries predominantly because of a high prevalence of modifiable risk factors. The Lipid Association of India (LAI) has provided a risk stratification algorithm for patients with ischaemic stroke and recommended low density lipoprotein cholesterol (LDL-C) goals for those in very high risk group and extreme risk group (category A) of

Defining type of diabetes using survey data is challenging, although important, for determining national estimates of diabetes. The purpose of this study was to compare the percentage and characteristics of US adults classified as having type 1 diabetes as defined by several algorithms.This study included 6331 respondents aged ≥18 years who reported a physician diagnosis of diabetes in the 2016-2017 National Health Interview Survey. Seven algorithms classified type 1 diabetes using various combinations of self-reported diabetes type, age of diagnosis, current and continuous insulin use, and use of oral hypoglycemics.The percentage of type 1 diabetes among those with diabetes ranged from 3.4% for those defined by age of diagnosis30 years and continuous insulin use (algorithm 2) to 10.2% for those defined only by continuous insulin use (algorithm 1) and 10.4% for those defined as self-report of type 1 (supplementary algorithm 6). Among those defined by age of diagnosis30 years and continuous insulin use (algorithm 2), by self-reported type 1 diabetes and continuous insulin use (algorithm 4), and by self-reported type 1 diabetes and current insulin use (algorithm 5), mean body mass index (BMI) (28.6, 27.4, and 28.5 kg/mEstimates of type 1 diabetes using commonly used algorithms in survey data result in varying degrees of prevalence, characteristic distributions, and potential misclassification.

Hypothesis: Partial Nephrectomy is oncological safe in patients with pT3a RCC. Purpose: To compare the oncological and functional outcomes of patients with pT3a RCC scheduled for PN and RN. Materials and Methods: We retrospectively reviewed patients with pT3a N0 M0 RCC who underwent partial or radical nephrectomy from 2005 to 2016. Perioperative characteristics, including estimated glomerular filtration rate, tumor size, pathological histology, and RENAL nephrometry score, were compared between patients scheduled for partial or radical nephrectomy. We used multivariable Cox proportional hazards regression models to compare overall survival, cancer-specific survival, and recurrence-free survival between planned procedure type. Results: Of the 589 patients, 369 (63%) and 220 (37%) were scheduled for radical and partial nephrectomy, respectively; 26 (12%) of the scheduled partial nephrectomy cases were intraoperatively converted to radical nephrectomy. After adjusting for tumor size and histology, there were no statistically significant differences in overall survival (hazard ratio 0.66; 95% CI, 0.38–1.13), cancer-specific survival (hazard ratio 0.53; 95% CI, 0.16–1.75), or recurrence-free survival (hazard ratio 0.66; 95% CI, 0.34–1.28) between patients scheduled for partial or radical nephrectomy. Fewer patients scheduled for partial nephrectomy had estimated glomerular filtration rate reductions 3 to 9 months after surgery than patients scheduled for radical nephrectomy. Conclusion: We found no evidence that patients scheduled to undergo partial nephrectomy had poorer oncologic outcomes than patients scheduled to undergo radical nephrectomy. In select patients with pT3a renal cell carcinoma in whom partial nephrectomy is deemed feasible by the surgeon, partial nephrectomy should not be discouraged.

Heterozygous familial hypercholesterolemia (HeFH) creates elevated low-density lipoprotein cholesterol (LDL-C), causing premature atherosclerotic cardiovascular disease (ASCVD). Guidelines recommend cascade screening relatives and starting statin therapy at 8–10 years old, but adherence to these recommendations is low. Our purpose was to measure self-reported physician practices for cascade screening and treatment initiation for HeFH using a survey of 500 primary care physicians and 500 cardiologists: 54% “always” cascade screen relatives of an individual with FH, but 68% would screen individuals with “strong family history of high cholesterol or premature ASCVD”, and 74% would screen a child of a patient with HeFH. The most likely age respondents would start statins was 18–29 years, with few willing to prescribe to a pediatric male (17%) or female (14%). Physicians who reported previously diagnosing a patient with HeFH were more likely to prescribe to a pediatric patient with HeFH, either male (OR = 1.34, 95% CI = 0.99–1.81) or female (OR = 1.31, 95% CI = 0.99–1.72). Many physicians do not cascade screen and are less likely to screen individuals with family history of known HeFH compared to “high cholesterol or premature ASCVD”. Most expressed willingness to screen pediatric patients, but few would start treatment at recommended ages. Further education is needed to improve diagnosis and treatment of HeFH.

The role of ST2 in stable coronary artery disease (CAD) has not yet been well defined. This study was performed to investigate baseline serum soluble ST2 (sST2) level can predict clinical outcomes in patients with stable CAD. A total of 388 consecutive patients with suspected CAD (65 years and 63.7% male) in stable condition referred for elective invasive coronary angiography (ICA) was prospectively recruited. Major adverse cardiovascular event (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization (90 days after ICA), and ischemic stroke during clinical follow-up was assessed. Most of the patients (88.0%) had significant CAD (stenosis ≥ 50%). During median follow-up of 834 days, there was 29 case of MACE (7.5%). The serum sST2 level was significantly higher in patients with MACE than those without (47.3 versus 30.6 ng/ml, P P = 0.011). The elevated level of baseline sST2 is associated with an increased risk of adverse clinical events in stable CAD patients. Studies with larger sample size are needed to confirm our findings.

The coronavirus disease 2019 (COVID-19) pandemic has created challenges for the provision of care for patients with diabetes. Increased physical distancing may worsen the preexisting disease burden and lead to progressively worse outcomes as a result of inadequate outpatient follow-up (1). In such an environment, the telehealth model may offer a valuable solution. However, there may be disparities in access to the internet, especially among individuals suffering from chronic medical conditions and minority patients, which may affect the implementation of the telehealth model. We aimed to assess 1 ) the disparities in internet access among those with hypertension or diabetes versus those without, 2 ) the disparities in internet access among Blacks and Hispanics compared with Whites, and 3 ) the extent of such disparities across the U.S. states. We used data from the 2016 to 2017 Behavioral Risk Factor Surveillance System (BRFSS), a nationwide telephone-based questionnaire administered by the Centers for Disease Control and Prevention among a random sample of U.S. adults regarding health-related behaviors, chronic health conditions, and the use of preventive services, to identify patients ≥18 years who reported having hypertension or diabetes (2). Participants were considered to have used the internet if they answered “Yes” to the question, “Have you used the internet in the past 30 days?” We analyzed these cross-sectional data using survey weights for BRFSS to account for the survey design. We used logistic regression models to study the association between hypertension, diabetes, race, and internet use …

Aims To describe the real‐world prevalence and consequences of hypertriglyceridaemia. Materials and methods We searched two large patient databases, the National Health and Nutrition Examination Survey (NHANES) database (2007–2014) and the Optum Research Database, as well as electronic medical records from two Kaiser Permanente regions. Results The NHANES data showed that ~26% of US adults, including nearly one‐third of statin users, had at least borderline hypertriglyceridaemia (triglycerides [TGs] ≥1.69 mmol/L), and ~40% of adults with diabetes had levels of ≥150 mg/dL despite statin use. The Optum analyses demonstrated that those with TG levels ≥1.69 mmol/L who were on statins had a significantly increased risk of composite initial major cardiovascular (CV) events (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.19–1.34; P

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.

The extent and relation of multisite atherosclerosis to cardiovascular disease (CVD) in metabolic syndrome (MetS) and diabetes (DM) are not well documented. We examined the extent of multisite atherosclerosis and its prognostic value for CVD events in MetS and DM.In CVD-free subjects from the Multi-Ethnic Study of Atherosclerosis, multisite atherosclerosis was measured as: (1) the number of arterial beds involved (coronary calcium0, abdominal aortic calcium0, carotid intima-media thickness ≥1 mm and ankle brachial index1 or ≥1.4); (2) a composite score summing the quartile rank for each atherosclerosis measure. Hazard ratios (HRs) and c-statistics were calculated for incident CVD and coronary heart disease (CHD) over 10.6 years.Of 1675 individuals (mean age 64 years, 51% male), 33.4% had MetS and 15.9% had DM. The number of atherosclerotic sites was higher in those with DM (mean ± SD = 1.67 ± 1.15) and MetS (1.49 ± 1.12) versus neither MetS/DM (1.09 ± 1.09) (p 0.0001). CVD rates per 1000 person-years ranged from 3.5, 8.2, and 10.0 in those with 0 sites positive to 35.1, 79.6 and 103.4 in those with 4 sites positive among neither DM/MetS, MetS and DM groups, respectively. HRs (95% CI) for CVD comparing those with 4 vs. 0 atherosclerotic sites were 4.0 (0.8-19.1), 4.9 (2.0-12.0), and 14.4 (3.6-57.6), respectively. C-statistics adding multisite atherosclerosis measures increased over models without the measures and with CIMT or ABI but not CAC.Multisite atherosclerosis is greater with MetS or DM, and predicts CVD and CHD events. Risk prediction is improved over CIMT and ABI but not CAC.

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.

Inflammation is a marker of arterial disease stemming from cholesterol-dependent to -independent molecular mechanisms. In recent years, the role of inflammation in atherogenesis has been underpinned by pharmacological approaches targeting systemic inflammation that have led to a significant reduction in cardiovascular disease (CVD) risk. Although the use of nutraceuticals to prevent CVD has largely focused on lipid-lowering (e.g, red-yeast rice and omega-3 fatty acids), there is growing interest and need, especially now in the time of coronavirus pandemic, in the use of nutraceuticals to reduce inflammatory markers, and potentially the inflammatory CVD burden, however, there is still not enough evidence to confirm this. Indeed, diet is an important lifestyle determinant of health and can influence both systemic and vascular inflammation, to varying extents, according to the individual nutraceutical constituents. Thus, the aim of this Position Paper is to provide the first attempt at recommendations on the use of nutraceuticals with effective anti-inflammatory properties.

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 (

Heterozygous familial hypercholesterolemia (HeFH) results in significant elevations in LDL-C and premature atherosclerotic cardiovascular disease (ASCVD). Current guidelines recommend add-on proprotein subtilisin/kexin type 9 inhibitor (PCSK9i) therapy for additional LDL-C lowering beyond statins. Data are sparse, however, regarding treatment patterns and barriers relating to PCSK9i in HeFH patients. We examined physician attitudes, use, and barriers for treatment in patients with HeFH. We surveyed 1,000 physicians (500 primary care providers [PCPs] and 500 cardiologists in the US regarding their preferred treatments, experience and barriers associated with using PCSK9is. Cardiologists compared to PCPs were more likely to rank a PCSK9i as most important for an HeFH patient needing additional LDL-C lowering (68.6% vs. 64.8%; p0.05), as well as prescribing and having a patient on a PCSK9i. PCPs vs. cardiologists were less likely (odds ratio [OR] [95% confidence interval] = 0.46 [0.34-0.63]), private vs. academic practice more likely (OR = 1.53 [1.02-2.28]), and those who would prescribe a PCSK9i in an HeFH patient with (OR = 3.86 [2.57-5.78]) or without (OR = 1.96 [1.40-2.72]) ASCVD needing additional LDL-C reduction beyond a statin were more likely to actually prescribe a PCSK9i. Those practicing in an urban vs. rural setting were less likely (OR = 0.56 [0.34-0.93]), and those indicating they would prescribe a PCKS9i in an HeFH patient with (OR = 2.80 [1.74-4.49]) or without (OR = 1.43 [1.02-2.02]) ASCVD needing additional LDL-C lowering beyond a statin were more likely to face difficulty prescribing a PCSK9i (all p0.05 to p0.01). Greater physician education and assistance among both cardiologists and PCPs are needed to address the gaps in understanding and treatment regarding PCSK9is.

HeFH is a common inherited disorder that leads to markedly elevated LDL-cholesterol from birth and premature cardiovascular disease. HeFH is frequently underdiagnosed and undertreated.To compare how well primary care physicians and cardiologists recognize and treat HeFH.The National Lipid Association surveyed 500 primary care physicians and 500 cardiologists in the US who have patients with baseline LDL-cholesterol ≥ 190 mg/dL. The survey was conducted between August 29 and September 30, 2019.For a hypothetical case of HeFH, 57% of cardiologists versus 43% of primary care physicians made the correct diagnosis (P0.001). Among respondents, 21% of cardiologists versus 29% of primary care physicians have never made a diagnosis of HeFH in a patient with an LDL-cholesterol ≥ 190 mg/dL (P0.004). Only 7% of cardiologists versus 5% of primary care physicians would refer to a lipid specialist (P=0.05). For additional LDL-cholesterol lowering after statins, 58% of cardiologists versus 48% of primary care physicians would prescribe a PCSK9 inhibitor (P=0.004); however, 30% of cardiologists versus 53% of primary care physicians have never prescribed a PSCK9 inhibitor in an HeFH patient (P0.001).Although cardiologists compared to primary care physicians are somewhat more likely to recognize and treat HeFH patients according to guidelines, both physician specialties do not adequately recognize or treat HeFH. There is a need for more education and training in recognizing and treating HeFH, greater access to lipid specialists, and fewer barriers for PCSK9 inhibitor use.

Background: Obesity is associated with an increased risk of heart failure (HF); however, how metabolic weight groups relate to HF risk, especially in postmenopausal women, has not been demonstrated. Methods: We included 19 412 postmenopausal women ages 50 to 79 without cardiovascular disease from the Women’s Health Initiative. Normal weight was defined as a body mass index ≥18.5 and 2 and waist circumference 2 or waist circumference ≥88 cm. Metabolically healthy was based on Results: Among our sample, 455 (2.34%) participants experienced HF hospitalizations over a mean follow-up time of 11.3±1.1 years. Compared with metabolically healthy normal weight individuals, HF risk was greater in metabolically unhealthy normal weight (HR, 1.66 [95% CI, 1.01–2.72], P =0.045) and metabolically unhealthy overweight/obese individuals (HR, 1.95 [95% CI, 1.35–2.80], P =0.0004), but not metabolically healthy overweight/obese individuals (HR, 1.15 [95% CI, 0.78–1.71], P =0.48). Subdividing the overweight/obese into separate groups showed HRs for metabolically unhealthy obese of 2.62 (95% CI, 1.80–3.83; P P =0.06). Conclusions: Metabolically unhealthy overweight/obese and metabolically unhealthy normal weight are associated with an increased risk of HF in postmenopausal women.

[This corrects the article DOI: 10.1016/j.ajpc.2020.100010.].

Our recent study has established that young blood factors are not causal, nor necessary, for the systemic rejuvenation of mammalian tissues. Instead, a procedure referred to as neutral blood exchange (NBE) that resets signaling milieu to a pro-regenerative state through dilution of old plasma, enhanced the health and repair of the muscle and liver, and promoted better hippocampal neurogenesis in 2-year-old mice (Mehdipour et al., Aging 12:8790–8819, 2020). Here we expand the rejuvenative phenotypes of NBE, focusing on the brain. Namely, our results demonstrate that old mice perform much better in novel object and novel texture (whisker discrimination) tests after a single NBE, which is accompanied by reduced neuroinflammation (less-activated CD68+ microglia). Evidence against attenuation/dilution of peripheral senescence-associated secretory phenotype (SASP) as the main mechanism behind NBE was that the senolytic ABT 263 had limited effects on neuroinflammation and did not enhance hippocampal neurogenesis in the old mice. Interestingly, peripherally acting ABT 263 and NBE both diminished SA-βGal signal in the old brain, demonstrating that peripheral senescence propagates to the brain, but NBE was more robustly rejuvenative than ABT 263, suggesting that rejuvenation was not simply by reducing senescence. Explaining the mechanism of the positive effects of NBE on the brain, our comparative proteomics analysis demonstrated that dilution of old blood plasma yields an increase in the determinants of brain maintenance and repair in mice and in people. These findings confirm the paradigm of rejuvenation through dilution of age-elevated systemic factors and extrapolate it to brain health and function. Supplementary Information The online version contains supplementary material available at 10.1007/s11357-020-00297-8.

Background We sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals. Methods This was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm3) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software ( Results In the final population of 2068 participants (59% males, 56 ± 9 years), those with MetS (n = 280;13.5%) had a greater prevalence of NAFLD (26.0% vs. 9.9%), higher EAT volume (114.1 cm3 vs. 73.7 cm3), and lower EAT attenuation (−76.9 HU vs. −73.4 HU; all p Conclusions MetS, NAFLD, and artificial intelligence-based EAT measures predict long-term MACE risk in asymptomatic individuals. Imaging biomarkers of cardiometabolic disease have the potential for integration into routine reporting of CAC scoring CT to enhance cardiovascular risk stratification. Trial registration NCT00927693.

Nearly 500 million adults worldwide currently have diabetes, a number expected to increase to 700 million over the next 25 years, largely fueled by the obesity epidemic and unhealthy lifestyles. Atherosclerotic cardiovascular disease (ASCVD), including coronary heart disease, stroke, heart failure, and peripheral arterial disease, is among the most common causes of death in persons with diabetes. However, diabetes is associated with great heterogeneity in ASCVD risks, warranting the need for cardiovascular risk assessment, including global risk scoring and consideration of risk-enhancing factors and subclinical atherosclerosis. Moreover, few persons with diabetes are at recommended targets for key ASCVD risk factors including LDL-cholesterol, blood pressure, HbA1c, nonsmoking status, and body mass index. Key treatment approaches focus on lifestyle modification, weight control, avoidance of cigarette smoking, and management of lipids, blood pressure, and blood glucose. For higher-risk patients, antiplatelet therapy is included. Blood pressure medication, statins, and, most recently, icosapent ethyl, have evidence for reducing ASCVD events in persons with diabetes. Newer medications for diabetes, including SGLT2 inhibitors and GLP-1 receptor agonists, also reduce cardiovascular events independent of level of HbA1c. Both classes prevent further kidney function deterioration while the SGLT2 inhibitors also reduce heart failure hospitalizations. Most importantly, a multidisciplinary team is required to address the myriad cardiovascular and other risks in persons with diabetes.

The relation between elevated lipoprotein(a) and total atherosclerotic cardiovascular disease (ASCVD) residual risk in persons with known cardiovascular disease on statin therapy is not well-established. We examined first and total recurrent ASCVD event risk in statin-treated adults with prior ASCVD. We studied 3,359 adults (mean age 63.6 years, 85.1% male) with prior ASCVD on statin therapy from the AIM-HIGH clinical trial cohort. The first and total ASCVD event rates were calculated by lipoprotein(a) [Lp(a)] categories. Cox regression and Prentice, Williams and Peterson (PWP) models provided hazard ratios (HRs) for ASCVD events over a mean follow-up of 3.3 years, adjusted for age, gender, trial treatment, LDL-C, and other risk factors. A total of 747 events occurred during follow-up, among which 544 were first events. First and total ASCVD event rates were greater with higher Lp(a) levels. Compared with Lp(a)

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: It is not well quantified if diabetes mellitus (DM) as a cardiovascular disease (CVD) risk equivalent depends on DM severity and other CVD risk factors. Methods: We pooled 4 US community-based cohorts (ARIC, JHS, MESA, FHS Offspring) and classified subjects by baseline DM/CVD status. DM+/CVD- was further classified by DM duration, HbA1c control or DM medication. Hazard ratios (HR) were estimated for CVD during a median follow-up of 14 years. Subgroup analysis comparing the HR of DM+/CVD- vs. DM-/CVD+ was done by CVD risk factors. We integrated all factors that impacted DM-conferred CVD risk and defined one with DM+/CVD- as CVD risk equivalent when his/her CVD risk was as high or higher than that if he/she had DM-/CVD+. CVD risk profile and event risk were compared between the CVD risk equivalent subgroups in DM+/CVD-. Results: The pooled cohort included 27,732 adults (mean age of 58 years, 45% males). CVD event rates per 1000 P-Y were 16.3, 33.3, 40.9 and 69.0 among those with DM-/CVD-, DM+/CVD-, DM-/CVD+ and DM+/CVD+, respectively. DM participants with HbA1c≥7%, DM duration over 10 years, or DM medication use had similar CVD risk as those with DM-/CVD+ while those without these factors had lower CVD risk; DM+/CVD- had similar CVD risk as those DM-/CVD+ among women, age Conclusion: Among CVD-free adults with DM, fewer than 20% are actually CVD risk equivalents. Poor HbA1c control, long DM duration, and current diabetes medication use were identified as predictors of CVD risk equivalent status and DM was more detrimental for CVD risk if one is female, younger age, White, or with high triglycerides. These risk enhancing factors should be considered in the treatment decision.

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: 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.

Background Despite established treatments, patients with type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS) are at higher risk of ischemic cardiovascular (CV) events and hospitalization for heart failure (HHF) compared to those without T2DM. LDL-C lowering or use of GLP-1 agonists predominantly affects ischemic CV events, with little effect on HHF. Conversely, treatment with SGLT-2 inhibitors reduces HHF, with less effect on ischemic CV events. Preclinical studies indicate that bromodomain and extra-terminal (BET) proteins coordinate gene transcription for pathways that promote atherothrombotic events as well as heart failure. We assessed the clinical effect of apabetalone (APB), a novel BET protein inhibitor, on a composite of non-fatal ischemic CV events, HHF, and CV death in a post hoc analysis of the BETonMACE trial Methods BETonMACE was a double-blind, placebo-controlled phase 3 study in patients with T2DM and recent acute coronary syndrome receiving standard of care risk factor management. In 13 countries, 2425 patients were enrolled. We conducted a time-to-event analysis for first adjudicated CV death or non-fatal MI, stroke, or HHF using a log-rank test and Cox proportional hazards model. Results At baseline median age was 62 years, 25.6% were female, 87.6% white, and use of high intensity statin, ACE inhibitors/ angiotensin II blockers, dual antiplatelet therapy and beta blocker were 90, 88, 92 and 91% respectively. A total of 312 subjects had an endpoint event, with 139 (11.5%) patients in the ABP group and 173 (14.3%) among PBO (HR 0.78, 95% CI 0.63–0.98, p=0.03, Figure). At 26 months, the absolute risk reduction was 3.2% and number needed to treat was 31. Numerically favorable HRs were observed for each component endpoint except for stroke (Table). Conclusion This present analysis suggests that BET inhibition with APB may be a novel pathway through which to reduce both HHF and ischemic CV events in high risk patients with T2DM thus impacting broader clinical outcomes with potentially large benefits for patients and healthcare systems. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Resverlogix Corp

Aims THEMIS ( NCT01991795 ) demonstrated cardioprotective benefits of ticagrelor plus acetylsalicylic acid (ASA) compared with placebo plus ASA in patients with type 2 diabetes (T2D), stable coronary artery disease (CAD) and no history of myocardial infarction (MI) or stroke. To complement these findings, we assessed clinical outcomes and healthcare costs in commercially insured US patients similar to those in THEMIS. Methods This retrospective, observational study used data from Optum. The T2D-CAD cohort (n = 154,369) included patients (≥50 years old) either with high cardiovascular risk or taking a P2Y12 inhibitor. The THEMIS-like cohort (n = 126,938) comprised patients (≥50 years old) at high cardiovascular risk; the THEMIS-PCI-like cohort comprised a subset of these patients with prior percutaneous coronary intervention (PCI) (n = 18,394). Results Mean follow-up was 2.4–2.5 years. Incidence rates of the composite outcome (death, MI, and stroke) were 6.56 (95% CI 6.50–6.63), 6.21 (6.14–6.28), and 5.57 (5.39–5.74) per 100 person-years, and annualized healthcare costs per patient were US$15,848, US$16,044, and US$20,934 for the T2D-CAD, THEMIS-like, and THEMIS-PCI-like cohorts, respectively. Conclusions Commercially insured patients similar to those in THEMIS had high cardiovascular event rates and healthcare costs, highlighting a need for improved preventive strategies.

OBJECTIVE While diabetes has been previously noted to be a stronger risk factor for cardiovascular disease (CVD) in women compared with men, whether this is still the case is not clear. Coronary artery calcium (CAC) predicts coronary heart disease (CHD) and CVD in people with diabetes; however, its sex-specific impact is less defined. We compared the relation of CAC in women versus men with diabetes for total, CVD, and CHD mortality. RESEARCH DESIGN AND METHODS We studied adults with diabetes from a large registry of patients with CAC scanning with mortality follow-up over 11.5 years. Cox regression examined the relation of CAC with mortality end points. RESULTS Among 4,503 adults with diabetes (32.5% women) aged 21–93 years, 61.2% of women and 80.4% of men had CAC >0. Total, CVD, and CHD mortality rates were directly related to CAC; women had higher total and CVD death rates than men when CAC >100. Age- and risk factor–adjusted hazard ratios (HRs) per log unit CAC were higher among women versus men for total mortality (1.28 vs. 1.18) (interaction P = 0.01) and CVD mortality (1.47 vs. 1.27) (interaction P = 0.04) but were similar for CHD mortality (1.48 and 1.48). For CVD mortality, HRs with CAC scores of 101–400 and >400 were 3.67 and 6.27, respectively, for women and 1.63 and 3.48, respectively, for men (interaction P = 0.04). For total mortality, HRs were 2.56 and 4.05 for women, respectively, and 1.88 and 2.66 for men, respectively (interaction P = 0.01). CONCLUSIONS CAC predicts CHD, CVD, and all-cause mortality in patients with diabetes; however, greater CAC predicts CVD and total mortality more strongly in women.

Ocular rosacea is a chronic inflammatory condition that can occur in the absence of cutaneous features. The most common ocular features are chronic blepharoconjunctivitis with eyelid margin inflammation and meibomian gland dysfunction. Corneal complications include corneal vascularization, ulceration, scarring and, rarely, perforation. Diagnosis is largely based on clinical signs, although it is often delayed in the absence of cutaneous changes, particularly in children. It can also be associated with systemic disorders such as cardiovascular disease. Management ranges from local therapy to systemic treatment, depending on the severity of the disease. In this review, we describe the epidemiology, pathophysiology, clinical features and treatment of rosacea and ocular rosacea.

AimsTo compare cardiovascular risk factor control in adults with diabetes participating in a national diabetes registry to those in the general population and to ascertain regional differences in diabetes care.MethodsAdults with diagnosed diabetes in the Diabetes Collaborative Registry (DCR) were compared with those in the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2016; standardized mean difference (SMD) > 0.2 defined significance. Regional differences were assessed in the DCR cohort; p

Despite statin therapy, many patients with atherosclerotic cardiovascular disease (ASCVD) still suffer from ASCVD events. Predictors of residual ASCVD risk are not well-delineated. We aimed to develop an ASCVD risk prediction model for patients with prior ASCVD on statin use. We utilized statin-treated patients with ASCVD from the AIM-HIGH trial cohort. A 5-year risk score for subsequent ASCVD events with known ASCVD was developed using Cox regression, including potential risk factors with age, sex, and race forced in the model. Internal discrimination and calibration were evaluated. We included 3,271 patients with ASCVD (85.4% male, mean age 63.6 years, 65% on moderate and 24% on high-intensity statin) with complete risk factor data and mean follow-up of 4.18 years. Overall, the estimated 5-year ASCVD risk was 21.1%: 10.2% of patients had a 5-year risk of >30%, and 38.8% had risk of between 20-30%. In the model, male sex, hemoglobin A1c, alcohol use (inversely), family history of cardiovascular disease, body mass index, serum creatinine, homocysteine, history of heart failure, history of carotid artery disease and lipoprotein(a) predicted residual ASCVD risk. Niacin treatment status did not enter the model. A C-statistic of 0.59 was obtained, with the Greenwood-Nam-D’Agostino test showing excellent calibration. We developed a risk prediction risk model for predicting 5-year residual ASCVD risk in statin-treated patients with known ASCVD that may help in identifying such persons at the highest risk of recurrent events. Validation in larger samples with patients on high-intensity statin is needed.