REDUCE-IT Eligibility and Preventable Cardiovascular Events in the US Population (from the National Health and Nutrition Examination Survey [NHANES]).

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, HbA1c <10%, blood pressure <200/100 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.

LEADER Trial Eligibility and Preventable Cardiovascular Events in US Adults with Diabetes: the National Health and Nutrition Examination Surveys 2007-2016.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Estimating the number of preventable cardiovascular disease events in the United States using the EMPA-REG OUTCOME trial results and National Health and Nutrition Examination Survey.

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.

Residual Hypertriglyceridemia and Estimated Atherosclerotic Cardiovascular Disease Risk by Statin Use in U.S. Adults With Diabetes: National Health and Nutrition Examination Survey 2007-2014.

OBJECTIVE: Hypertriglyceridemia (HTG) is common in patients with diabetes, and statins remain the first-line therapy. However, the proportion of patients with diabetes having elevated triglycerides (TGs) on statin treatment and their atherosclerotic cardiovascular disease (ASCVD) risk has not been described. We quantified the prevalence of HTG in U.S. adults with diabetes currently treated versus not treated with statins and the estimated 10-year ASCVD risk. RESEARCH DESIGN AND METHODS: Among 1,448 U.S. adults aged 20 years and over with diabetes (projected to 24.4 million) in the 2007-2014 National Health and Nutrition Examination Survey (NHANES), we compared the prevalence of borderline HTG (TG 150-199 mg/dL) and HTG (TG ≥200 mg/dL) by statin use and LDL cholesterol (LDL-C) levels, and we used logistic regression to identify risk factors for HTG. We also estimated the 10-year ASCVD risk in those without prior ASCVD. RESULTS: The prevalence of borderline HTG and HTG was 20.0% and 19.5%, respectively, in statin users and 20.1% and 25.3%, respectively, in nonstatin users (P < 0.0001). Even among statin users with LDL-C <70 mg/dL, borderline HTG prevalence was 16.8% and HTG prevalence was 16.7%. Approximately 77.5% of those with HTG had an estimated 10-year ASCVD risk of ≥7.5%, with almost 40% of statin users having ASCVD risk ≥20%. CONCLUSIONS: Residual HTG occurs in over one-fifth (∼5.5 million) of U.S. adults with diabetes, including those on statin therapy and with well-controlled LDL-C. Over three-quarters of adults with diabetes with HTG are at moderate or high 10-year risk for ASCVD. Greater efforts are needed to promote lifestyle and pharmacologic means to address residual HTG.

Hypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey.

BACKGROUND: Statin therapy remains the primary treatment for mixed dyslipidemia, even with moderate triglyceride (TG) elevations. OBJECTIVE: 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. METHODS: 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. RESULTS: 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 cholesterol <100 mg/dL (or <70 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. CONCLUSIONS: 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.

Effects of Glutamate and Aspartate on Serum Antioxidative Enzyme, Sex Hormones, and Genital Inflammation in Boars Challenged with Hydrogen Peroxide.

Background. Oxidative stress is associated with infertility. This study was conducted to determine the effects of glutamate and aspartate on serum antioxidative enzymes, sex hormones, and genital inflammation in boars suffering from oxidative stress. Methods. Boars were randomly divided into 4 groups: the nonchallenged control (CON) and H2O2-challenged control (BD) groups were fed a basal diet supplemented with 2% alanine; the other two groups were fed the basal diet supplemented with 2% glutamate (GLU) or 2% aspartate (ASP). The BD, GLU, and ASP groups were injected with hydrogen peroxide (H2O2) on day 15. The CON group was injected with 0.9% sodium chloride solution on the same day. Results. Dietary aspartate decreased the malondialdehyde (MDA) level in serum (P < 0.05) compared with the BD group. Additionally, aspartate maintained serum luteinizing hormone (LH) at a relatively stable level. Moreover, glutamate and aspartate increased transforming growth factor-ß1 (TGF-ß1) and interleukin-10 (IL-10) levels in the epididymis and testis (P < 0.05) compared with the BD group. Conclusion. Both glutamate and aspartate promoted genital mRNA expressions of anti-inflammatory factors after oxidative stress. Aspartate more effectively decreased serum MDA and prevented fluctuations in serum sex hormones after H2O2 challenge than did glutamate.

Proteomic analysis for anti-atherosclerotic effect of tetrahydroxystilbene glucoside in rats.

2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) extracted from Polygonum multiflorum (a traditional Chinese medicinal herb) has been proved to exhibit significant anti-atherosclerotic activity. In this study, we firstly used proteomic analyses to investigate the molecular events occurring in the atherosclerotic rats after TSG treatment. Aortic samples were collected from the atherosclerotic rat group and the TSG-treated group, and its proteome was analyzed by two-dimensional gel electrophoresis (2-DE). Proteins showing significant changes in expression were identified and analyzed by matrix-assisted desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). As a result, 21 protein spots were found with significant differential expression after the treatment with TSG. A total of 18 spots were identified by database searching, and 17 spots matched with known proteins. Among these proteins (11 proteins up-regulated and six proteins down-regulated), five proteins were mainly involved in inflammation, cholesterol transport, cell apoptosis and adhesion. TSG treatment enhanced the expression of HSP 70, lipocortin 1 and Apo A-I, and inhibited the expression of calreticulin, vimentin. Furthermore, we randomly selected four proteins and confirmed the results of proteomic analysis by RT-PCR and western blotting. In conclusion, TSG treatment suppresses atherosclerosis by altering the expression of different proteins. Calreticulin, vimentin, HSP 70, lipocortin 1, and Apo A-I, are key proteins that may be novel molecular targets responsible for atherogenesis suppression induced by TSG treatment.