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OBJECTIVE: To examine by secondary analysis of the Treating to New Targets (TNT) study whether the benefits of intensive versus standard levels of lipid lowering are equally applicable to women. METHODS: A total of 10 001 patients (1902 women) with stable coronary heart disease (CHD) were randomised to double-blind treatment with atorvastatin 10 or 80 mg/day for a median follow-up of 4.9 years. RESULTS: In women and men, intensive treatment with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events compared with atorvastatin 10 mg. Among women, the relative and absolute reductions were 27% and 2.7%, respectively (hazard ratio (HR) = 0.73, 95% confidence interval (CI) 0.54 to 1.00, p = 0.049). In men, the corresponding rate reductions were 21% and 2.2% (HR = 0.79, 95% CI 0.69 to 0.91, p = 0.001). The number needed to treat value (to prevent one cardiovascular event over 4.9 years compared with patients treated with atorvastatin 10 mg) for atorvastatin 80 mg was 29 for women and 30 for men. Rates of death of non-cardiovascular origin in the atorvastatin 80 mg and atorvastatin 10 mg were 3.6% and 1.6%, respectively (p = 0.004) among women, and 2.8% and 3.1% (p = 0.47) among men. CONCLUSION: Intensive lipid-lowering treatment with atorvastatin 80 mg produced significant reductions in relative risk for major cardiovascular events compared with atorvastatin 10 mg in both women and men with stable CHD. [ABSTRACT FROM AUTHOR]

Background: Increased life expectancy is associated with an increase in the burden of chronic cardiovascular disease.Objective: To assess the efficacy and safety of high-dose atorvastatin in patients 65 years of age or older.Design: A prespecified secondary analysis of the Treating to New Targets study, a randomized, double-blind clinical trial.Setting: 256 sites in 14 countries participating in the Treating to New Targets study.Participants: 10,001 patients (3809 patients > or =65 years of age) with coronary heart disease (CHD) and low-density lipoprotein cholesterol levels less than 3.4 mmol/L (<130 mg/dL).Intervention: Patients were randomly assigned to receive atorvastatin, 10 or 80 mg/d.Measurements: The primary end point was the occurrence of a first major cardiovascular event (death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke).Results: In patients 65 years of age or older, absolute risk was reduced by 2.3% and relative risk by 19% for major cardiovascular events in favor of the high-dose atorvastatin group (hazard ratio, 0.81 [95% CI, 0.67 to 0.98]; P = 0.032). Among the components of the composite outcome, the mortality rates from CHD, nonfatal non-procedure-related myocardial infarction, and fatal or nonfatal stroke (ischemic, embolic, hemorrhagic, or unknown origin) were all lower in older patients who received high-dose atorvastatin, although the difference was not statistically significant for each individual component. The improved clinical outcome in patients 65 years of age or older was not associated with persistent elevations in creatine kinase levels.Limitation: Because the study was a secondary analysis, the findings should be interpreted within the context of the main study results.Conclusions: The analysis suggests that additional clinical benefit can be achieved by treating older patients with CHD more aggressively to reduce low-density lipoprotein cholesterol levels to less than 2.6 mmol/L (<100 mg/dL). The findings support the use of intensive low-density lipoprotein cholesterol-lowering therapy in high-risk older persons with established cardiovascular disease. Click here for related information on atorvastatin. [ABSTRACT FROM AUTHOR]

Presents an introduction to March 1, 2003 issue of the "Journal of Women's Health."

Higher coronary artery calcium (CAC) scores and progression of CAC are associated with higher mortality. We previously reported that subjects with coronary artery disease randomly allocated to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation or none had similar significant increases in CAC score over 30 months. Whether these findings are influenced by diabetes status is unknown. A total of 242 subjects with coronary artery disease who were on statin therapy were randomly allocated to to 1.86 g EPA and 1.5 g DHA daily or none (control). The CAC score was measured at baseline and 30-month follow-up using noncontrast, cardiac computed tomography. A significant interaction term between diabetes status and treatment arm was noted in the prediction of the CAC score (p <0.001). A total of 176 subjects (85.8% men) had no diabetes and 66 subjects (80.3% men) had diabetes. The mean age was 62.9 ± 7.9 versus 63.2 ± 7.1 years, respectively. The mean low-density lipoprotein cholesterol and median triglyceride levels were not significantly different between those without and with diabetes: 77.7 ± 25.9 versus 77.1 ± 30.2 mg/100 ml, respectively, and 117.0 (78.0 to 158.0) versus 119.0 (84.5 to 201.5) mg/100 ml, respectively. Subjects with diabetes on EPA+DHA had a greater increase in CAC score than subjects with diabetes in the control group (median 380.7 vs 183.5, respectively, p = 0.021). In contrast, no difference occurred between the EPA+DHA and control groups in subjects without diabetes (175.7 vs 201.1, respectively, p = 0.41). In conclusion, EPA+DHA supplementation was associated with greater CAC progression in subjects with diabetes than subjects with diabetes in the control group over a 30-month period; whether this indicates progression of the disease burden or plaque stabilization requires further study., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation lower triglyceride levels. The impact on epicardial adipose tissue volume (EATV), which is associated with cardiovascular events, is unclear., Objective: To determine if triglyceride reduction with EPA+DHA supplementation decreases EATV and whether EATV affects coronary plaque., Methods: 139 subjects with coronary artery disease on statins were randomized to 3.36 g EPA+DHA daily or none (control) for 30 months. EATV, coronary plaque volumes and coronary artery calcium score were measured with coronary computed tomographic angiography., Results: Change in triglyceride level correlated with change in EATV (r=0.236; p=0.006). Despite a 6.7% triglyceride reduction (p=0.021) with EPA+DHA supplementation compared to no change in control (between group p=0.034); both groups had similar reductions in EATV possibly due to statin treatment. EATV above the median (>115.6 cm 3 ) was the only determinant of baseline coronary fatty plaque volume (β=2.4, p=0.010). After multivariate adjustment, waist circumference, a surrogate of abdominal visceral adiposity, was the only determinant of baseline EATV (OR:1.093; 95% CI:1.003-1.192, p=0.042). Moreover, increase in waist circumference was the only predictor of an increase in EATV at 30 months (β=0.320, p=0.018)., Conclusions: EATV is associated with higher coronary fatty plaque volume and is regulated by waist circumference but not EPA+DHA supplementation at 30-month follow-up in CAD patients on statin treatment. The direct correlation between waist circumference and EATV suggests that maintaining a healthy weight may limit EATV and coronary fatty plaque volume, potentially leading to a decrease in cardiovascular events. Two sentence summary Subjects with clinical CAD on statin treatment randomized to EPA+DHA had similar reductions in epicardial adipose tissue volume (EATV) compared to control, despite a significant reduction in triglyceride level in the EPA+DHA group. Higher EATV was linked to greater fatty, rupture-prone plaques, boosting the risk of MI, and change in waist circumference was the only predictor of an increase in EATV at 30-month follow-up., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier Inc.)

Both cardiovascular disease (CVD) and cognitive decline are common features of aging. One in 5 deaths is cardiac for both men and women in the United States, and an estimated 50 million are currently living with dementia worldwide. In this review, we summarize sex and racial differences in the role of fish and its very long chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in preventing CVD events and cognitive decline. In prospective studies, women with higher nonfried and fatty fish intake and women and Black individuals with higher plasma levels of EPA and DHA had a lower risk of CVD. In randomized controlled trials of EPA and DHA supplementation in primary CVD prevention, Black subjects benefited in a secondary outcome. In secondary CVD prevention, both men and women benefited, and Asians benefited as a prespecified subgroup. Fish and omega-3 polyunsaturated fatty acids are associated with prevention of cognitive decline in prospective studies. In randomized controlled trials of EPA and DHA supplementation, women have cognitive benefit. DHA seems more beneficial than EPA, and supplementation is more beneficial when started before cognitive decline. Although studies in women and racial groups are limited, life-long intake of nonfried and fatty fish lowers the risk of CVD and cognitive decline, and randomized controlled trials also show the benefit of EPA and DHA supplementation. These findings should be factored into recommendations for future research and clinical recommendations as dietary modalities could be cost-effective for disease prevention., Competing Interests: Disclosures None.

Background and Aims: We previously reported that an omega-3 fatty acid index ≥4% with high-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) prevented progression of noncalcified plaque. Higher coronary artery calcium (CAC) scores and progression of CAC are associated with increased cardiovascular events and mortality. We examined the effect of EPA + DHA on CAC score., Methods: A total of 242 patients with coronary artery disease (CAD) on statin therapy were randomized to 1.86 g EPA and 1.5 g DHA daily or none (control) for 30 months. The CAC score was measured at baseline and 30-months with non-contrast, cardiac computed tomography., Results: Both EPA + DHA and control groups had significant progression in CAC scores over 30 months (median change:183.5 vs 221.0, respectively, p < 0.001) despite a 13.6% reduction in triglyceride level with EPA + DHA. No significant difference was observed between groups for the total group, by baseline CAC scores of <100, 100-399, 400-999 and ≥1000 or quartiles of achieved levels of EPA, DHA and the omega-3 fatty acid index. Similar rates of CAC progression were noted in those on high-intensity statin compared to low- and moderate-intensity statin., Conclusions: EPA and DHA added to statin resulted in similar CAC progression over 30 months regardless of baseline CAC categories, statin intensity and achieved levels of EPA, DHA and the omega-3 fatty acid index., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Aims: Higher coronary artery calcium (CAC) scores are associated with increased cardiovascular (CVD) events and mortality. Exercise capacity is predictive of CVD events. Our aim was to examine the relationship between exercise capacity and CAC in women and men., Methods: CAC was measured in 203 men and 38 women with clinical coronary artery disease using multidetector coronary tomography. They were randomized to 3.36 g eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily or none for 30 months. Maximal exercise treadmill testing was performed at baseline with calculation of metabolic equivalents of task (METs) achieved as a measure of exercise capacity., Results: Despite similar ages at baseline (64.0 ± 6.7 vs 62.7 ± 7.8 years, respectively, p = 0.225), women had lower CAC scores compared to men: 106.7 Agatston units [AU] vs 535.3, respectively, p < 0.001, and at every age (p < 0.001). Female CAC scores did not equal those of men until women were 20 years older. Higher levels of METs were associated with lower CAC scores in both women and men. After multivariate adjustment, METs was the most important predictor of CAC score in women at baseline and 30 months (p = 0.001 and 0.029, respectively) whereas only age predicted in men (p = 0.019 and 0.004, respectively). Annual CAC progression was significantly greater in men compared to women (94.8 AU/year vs 38.0, respectively, p = 0.014). No difference was observed in CAC progression in the EPA + DHA group compared to control in either men or women., Conclusions: The association of higher METs with lower CAC scores in both women and men supports recommending exercise to maximize cardiorespiratory fitness as this may minimize CAC scores and thus, potentially decrease risk for CVD events. This may be especially important for women since METs independently predicted baseline and 30 month CAC in women., Competing Interests: Declaration of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: Postoperative atrial fibrillation (POAF) is a common complication in the acute care period following coronary artery bypass grafting (CABG) surgery that is associated with significant morbidity and mortality in both short-term and long-term settings. Recently, the Vaughn Williams Classification of antiarrhythmic agents, first proposed in 1975 and widely viewed as the authoritative description of their electrophysiologic actions, was updated and notably omega-3 fatty acids (Ω-3 fatty acids) have been included in class VII, described as "upstream target modulators," to mitigate pathological structural and electrophysiological remodeling changes in the aged and/or injured myocardium., Data Sources: A PubMed literature search was performed., Study Selection: Studies examining the significance of complications in patients undergoing isolated CABG surgery were selected for inclusion., Data Extraction: Relevant data were qualitatively assessed and narratively summarized., Data Synthesis: POAF occurs in approximately 30% of patients, and inflammation from chronic coronary artery disease preoperatively, as well as acute atrial inflammation from surgery postoperatively are the leading causes. Inflammation underlies its pathophysiology; therefore Ω-3 fatty acids not only exhibit antiarrhythmic properties but are an effective anti-inflammatory treatment that may reduce the clinical risks of POAF., Conclusions: At present no effective prophylaxis is available to address POAF following CABG surgery. Clinical approaches that focus on the inflammatory response in this setting may optimize the response to treatment. The current literature supports the hypothesis that Ω-3 fatty acids may acutely reduce the inflammatory response via favorable alterations in the metabolism of prostaglandins and leukotrienes (eicosanoids) and specialized pro-resolving mediators., Competing Interests: Dr. Driscoll is inventor of U.S. Patent No. US 8,241,672 entitled “Omega-3 enriched fish oil-in-water parenteral nutrition emulsions,” filed on March 11, 2009. Dr. Bistrian is co-inventor of U.S. Patent No. 10,328,045 B2 entitled “Dietary emulsion formulations and methods for using the same, filed on September 10, 2015.” Dr. Welty has disclosed that she does not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background Residual risk of cardiovascular events and plaque progression remains despite reduction in low-density lipoprotein cholesterol. Factors contributing to residual risk remain unclear. The authors examined the role of eicosapentaenoic acid and docosahexaenoic acid in coronary plaque regression and its predictors. Methods and Results A total of 240 patients with stable coronary artery disease were randomized to eicosapentaenoic acid plus docosahexaenoic acid (3.36 g/d) or none for 30 months. Patients were stratified by regression or progression of coronary fatty plaque measured by coronary computed tomographic angiography. Cardiac events were ascertained. The mean±SD age was 63.0±7.7 years, mean low-density lipoprotein cholesterol level was <2.07 mmol/L, and median triglyceride level was <1.38 mmol/L. Regressors had a 14.9% reduction in triglycerides that correlated with fatty plaque regression ( r =0.135; P =0.036). Compared with regressors, progressors had higher cardiac events (5% vs 22.3%, respectively; P <0.001) and a 2.89-fold increased risk of cardiac events (95% CI, 1.1-8.0; P =0.034). Baseline non-high-density lipoprotein cholesterol level <2.59 mmol/L (100 mg/dL) and systolic blood pressure <125 mm Hg were significant independent predictors of fatty plaque regression. Normotensive patients taking eicosapentaenoic acid plus docosahexaenoic acid had regression of noncalcified coronary plaque that correlated with triglyceride reduction ( r =0.35; P =0.034) and a significant decrease in neutrophil/lymphocyte ratio. In contrast, hypertensive patients had no change in noncalcified coronary plaque or neutrophil/lymphocyte ratio. Conclusions Triglyceride reduction, systolic blood pressure <125 mm Hg, and non-high-density lipoprotein cholesterol <2.59 mmol/L were associated with coronary plaque regression and reduced cardiac events. Normotensive patients had greater benefit than hypertensive patients potentially due to lower levels of inflammation. Future studies should examine the role of inflammation in plaque regression. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01624727.

Therapeutic approaches to reduce atherogenic lipid and lipoprotein levels remain the most effective and assessable strategies to prevent and treat cardiovascular disease. The discovery of novel research targets linked to pathways associated with cardiovascular disease development has enhanced our ability to decrease disease burden; however, residual cardiovascular disease risks remain. Advancements in genetics and personalized medicine are essential to understand some of the factors driving residual risk. Biological sex is among the most relevant factors affecting plasma lipid and lipoprotein profiles, playing a pivotal role in the development of cardiovascular disease. This minireview summarizes the most recent preclinical and clinical studies covering the effect of sex on plasma lipid and lipoprotein levels. We highlight the recent advances in the mechanisms regulating hepatic lipoprotein production and clearance as potential drivers of disease presentation. We focus on using sex as a biological variable in studying circulating lipid and lipoprotein levels., Competing Interests: Disclosures None.

In this review, sex, racial, and ethnic differences in acute coronary syndromes on a global scale are summarized. The relationship between disparities in presentation and management of acute coronary syndromes and effect on worse clinical outcomes in acute coronary syndromes are discussed. The effect of demographic, geographic, racial, and ethnic factors on acute coronary syndrome care disparities are reviewed. Differences in risk factors including systemic inflammatory disorders and pregnancy-related factors and the pathophysiology underlying them are discussed. Finally, breast arterial calcification and coronary calcium scoring are discussed as methods to detect subclinical atherosclerosis and start early treatment in an attempt to prevent clinical disease., Competing Interests: Disclosures None.

Asian American individuals make up the fastest growing racial and ethnic group in the United States. Despite the substantial variability that exists in type 2 diabetes and atherosclerotic cardiovascular disease risk among the different subgroups of Asian Americans, the current literature, when available, often fails to examine these subgroups individually. The purpose of this scientific statement is to summarize the latest disaggregated data, when possible, on Asian American demographics, prevalence, biological mechanisms, genetics, health behaviors, acculturation and lifestyle interventions, pharmacological therapy, complementary alternative interventions, and their impact on type 2 diabetes and atherosclerotic cardiovascular disease. On the basis of available evidence to date, we noted that the prevalences of type 2 diabetes and stroke mortality are higher in all Asian American subgroups compared with non-Hispanic White adults. Data also showed that atherosclerotic cardiovascular disease risk is highest among South Asian and Filipino adults but lowest among Chinese, Japanese, and Korean adults. This scientific statement discusses the biological pathway of type 2 diabetes and the possible role of genetics in type 2 diabetes and atherosclerotic cardiovascular disease among Asian American adults. Challenges to provide evidence-based recommendations included the limited data on Asian American adults in risk prediction models, national surveillance surveys, and clinical trials, leading to significant research disparities in this population. The large disparity within this population is a call for action to the public health and clinical health care community, for whom opportunities for the inclusion of the Asian American subgroups should be a priority. Future studies of atherosclerotic cardiovascular disease risk in Asian American adults need to be adequately powered, to incorporate multiple Asian ancestries, and to include multigenerational cohorts. With advances in epidemiology and data analysis and the availability of larger, representative cohorts, furthering refining the Pooled Cohort Equations, in addition to enhancers, would allow better risk estimation in segments of the population. Last, this scientific statement provides individual- and community-level intervention suggestions for health care professionals who interact with the Asian American population.

Purpose of Review: The aim is to provide an update on omega-3 polyunsaturated fatty acids (n-3 PUFA) in preventing cognitive decline and dementia., Recent Findings: Prospective studies and three new meta-analyses suggest that fish or n-3 PUFA intake are associated with a reduction in development of mild cognitive decline and Alzheimer's disease. Supplementation with docosahexaenoic acid (DHA) in randomized controlled trials (RCTs) in those with mild cognitive impairment showed benefit on cognitive decline, whereas there was no benefit in Alzheimer's disease. In cognitively healthy individuals with clinical coronary artery disease (CAD), 3.36 g EPA and DHA daily slowed cognitive ageing by 2.5 years. Of 15 RCTs in cognitively healthy individuals age more than 55 years, seven reported benefit, whereas eight did not. Potential mechanisms for differences in outcomes include dose, trial duration, apolipoproteinE genotype, sex, stage and rate of cognitive decline, cognitive testing employed and individual characteristics. The downstream product of DHA, neuroprotectin D1, may be involved in beneficial effects., Summary: Patients with early memory complaints or a family history of dementia and those with CAD should be counselled on the potential benefits of fish intake and supplementation with n-3 PUFA. ApolipoproteinE4 carriers may especially benefit from DHA supplementation prior to development of cognitive decline., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Limited data exist on the risk profile and outcomes among young patients with acute myocardial infarction(AMI) in low-and middle-income countries(LMICs). This study explored differences in the clinical characteristics, medical care, and outcomes of AMI in young adults in India with a subanalysis focusing on sex disparities amongst the young., Methods: Using the Acute Coronary Syndrome Quality Improvement in Kerala trial database, we compared baseline characteristics, management, and outcomes amongst the young patients(≤50 years) and their older counterparts. The primary outcomes were the rates of in-hospital and 30-day composite of in-hospital major adverse cardiovascular events(MACE)., Results: Of the 21,374 adults enrolled, 4762(22%) were young, of which 614 (12.9%) were females. Young patients with AMI were more likely to be smokers(41.9% vs. 27.8%; P  < 0.001) and undergo coronary angiography (66.3%vs.57.3%; P < 0.001) and percutaneous coronary intervention (PCI)(57.5% vs. 47.0%; P  < 0.001), compared to older patients. After adjustment for potential confounders, younger patients had a lower likelihood of in-hospital (RR = 0.49; 95%CI 0.40-0.61; P  < 0.001) and 30-day MACE (RR = 0.54; 95%CI 0.46-0.64; P  < 0.001). Subgroup analysis comparing young males and females revealed worse cardiovascular risk profile among young women except for smoking. In-hospital MACE(RR = 1.60; 95%CI, 1.0-2.45; P  = 0.048) were higher for young women compared to men., Conclusion: Young AMI patients had higher prevalence of modifiable risk factors, were more likely to receive reperfusion therapy, and had better short and intermediate outcomes, compared to older patients. Compared to young men with AMI, young women had worse cardiovascular risk profile, were less likely to be treated with diagnostic angiography or PCI and experienced higher in-hospital death and MACE., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background and Aims: High-dose eicosapentaenoic acid (EPA) therapy was beneficial in high-risk patients without clinical cardiovascular disease (CVD). Whether higher plasma levels of EPA and docosahexaenoic acid (DHA) have similar benefits in those without subclinical CVD is unclear. We aim to evaluate the interplay between plasma omega-3 fatty acids and coronary artery calcium (CAC) in relation to CVD events., Methods: We examined 6568 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with plasma EPA and DHA levels and CAC measured at baseline. The primary outcome was incident CVD events (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Hazard ratios for the primary outcome were adjusted for potential confounder using Cox regression., Results: Mean ± SD age was 62.1 ± 10.2 years and 52.9% were females. The median follow-up time was 15.6 years. Higher log e (EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.94) and log e (DHA) (aHR = 0.79; 95% CI, 0.66-0.96) were independently associated with fewer CVD events. The difference in absolute CVD event rates between lowest vs. highest EPA tertile increased at higher CAC levels. The adjusted HR for highest vs. lowest EPA tertile within CAC = 0 was 1.02 (95% CI, 0.72-1.46), CAC = 1-99 was 0.71 (95% CI, 0.51-0.99), and CAC≥100 was 0.67 (95% CI, 0.52-0.84). A similar association was seen in tertiles of DHA by CAC category., Conclusions: In an ethnically diverse population free of clinical CVD, higher plasma omega-3 fatty acid levels were associated with fewer long-term CVD events. The absolute decrease in CVD events with higher omega-3 fatty acid levels was more apparent at higher CAC scores., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is believed to affect >25% of adults worldwide. Unless specific testing is done to identify NAFLD, the condition is typically silent until advanced and potentially irreversible liver impairment occurs. For this reason, the majority of patients with NAFLD are unaware of having this serious condition. Hepatic complications from NAFLD include nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. In addition to these serious complications, NAFLD is a risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Accordingly, the purpose of this scientific statement is to review the underlying risk factors and pathophysiology of NAFLD, the associations with atherosclerotic cardiovascular disease, diagnostic and screening strategies, and potential interventions.

Background: Public acceptance of governmental measures are key to controlling the spread of infectious diseases. The COVID-19 pandemic has placed a significant burden on healthcare systems for high-income countries as well as low- and middle-income countries (LMICs). The ability of LMICs to respond to the challenge of the COVID-19 pandemic has been limited and may have affected the impact of governmental strategies to control the spread of COVID-19. This study aimed to evaluate and compare public opinion on the governmental COVID-19 response of high and LMICs in the Middle East and benchmark it to international countries., Methods: An online, self-administered questionnaire was distributed among different Middle Eastern Arab countries. Participants' demographics and level of satisfaction with governmental responses to COVID-19 were analyzed and reported. Scores were benchmarked against 19 international values., Results: A total of 7395 responses were included. Bahrain scored highest for satisfaction with the governmental response with 38.29 ± 2.93 on a scale of 40, followed by the Kingdom of Saudi Arabia (37.13 ± 3.27), United Arab Emirates (36.56 ± 3.44), Kuwait (35.74 ± 4.85), Jordan (23.08 ± 6.41), and Lebanon (15.39 ± 5.28). Participants' country of residence was a significant predictor of the satisfaction score (P < 0.001), and participants who suffered income reduction due to the pandemic, had a history of SARS-CoV-2 infection, and held higher educational degrees had significantly lower satisfaction scores (P < 0.001). When benchmarked with other international publics, countries from the Gulf Cooperation Council had the highest satisfaction level, Jordan had an average score, and Lebanon had one of the lowest satisfaction scores., Conclusion: The political crisis in Lebanon merged with the existing corruption were associated with the lowest public satisfaction score whereas the economical instability of Jordan placed the country just before the lowest position. On the other hand, the solid economy plus good planning and public trust in the government placed the other countries of the Gulf Cooperation Council on top of the scale. Further investigation is necessary to find out how the governments of other low-income countries may have handled the situation wisely and gained the trust of their publics. This may help convey a clearer picture to Arab governments that have suffered during the pandemic., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 and was first reported in December 2019 in Wuhan, China. Since then, it caused a global pandemic with 212,324,054 confirmed cases and 4,440,840 deaths worldwide as of August 22, 2021. The disease spectrum of COVID-19 ranges from asymptomatic subclinical infection to clinical manifestations predominantly affecting the respiratory system. However, it is now evident that COVID-19 is a multiorgan disease with a broad spectrum of manifestations leading to multiple organ injuries including the cardiovascular system. We review studies that have shown that the relationship between cardiovascular diseases and COVID-19 is indeed bidirectional, implicating that preexisting cardiovascular comorbidities increase the morbidity and mortality of COVID-19, and newly emerging cardiac injuries occur in the settings of acute COVID-19 in patients with no preexisting cardiovascular disease. We present the most up-to-date literature summary to explore the incidence of new-onset cardiac complications of coronavirus and their role in predicting the severity of COVID-19. We review the association of elevated troponin with the severity of COVID-19 disease, which includes mild compared to severe disease, in nonintensive care unit compared to intensive care unit patients and in those discharged from the hospital compared to those who die. The role of serum troponin levels in predicting prognosis are compared in survivors and non-survivors. The association between COVID-19 disease and myocarditis, heart failure and coagulopathy are reviewed. Finally, an update on beneficial treatments is discussed., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: The regulation of cell-cholesterol efflux is not completely understood. Our aim was to assess the role of HDL- and non-HDL-related parameters in ATP-binding cassette transporter-A1 (ABCA1) and scavenger receptor class B-type-I (SRBI) cell-cholesterol efflux capacity (CEC) in coronary heart disease (CHD) cases and controls., Methods: Lipids and apoA-I-containing HDL particles (by 2D gel-electrophoresis and immunodetection) were measured in 534 statin-treated CHD patients and in 1076 age-, gender-, and BMI-matched controls. ABCA1-CEC and SRBI-CEC were measured in apoB-depleted serum of 100 cases and 100 controls., Results: Cases had significantly higher concentrations of preβ-1 particles (88%) and ABCA1-CEC (34%) compared to controls. ABCA1-CEC was positively correlated with the concentrations of preβ-1 particles, triglycerides, small-dense (sd) LDL-C, and LDL-C in both cases and controls. Moreover, both the concentration and the functionality of preβ-1 particles (ABCA1-CEC/mg preβ-1) were positively associated with the concentrations of sdLDL-C and triglycerides. Cases had 27% lower levels of large HDL particles but similar SRBI-CEC compared to controls. SRBI-CEC was correlated positively with HDL-C, apoA-I, and large-HDL particle levels. However, the functionality of large-HDL particles (SRBI-CEC/mg large particles) was significantly and positively correlated with the preβ-1/α-1 ratio, sdLDL-C, and triglycerides., Conclusions: CHD patients have significantly higher concentration, but less functional preβ-1 particles in term of cholesterol efflux capacity compared to controls. Triglyceride-rich lipoproteins have significant influence on either the concentration or the functionality or both of HDL particles and consequently HDL-CEC., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background Randomized trials of pharmacologic strength omega-3 fatty acid (n3-FA)-based therapies suggest a dose-dependent cardiovascular benefit. Whether blood n3-FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3-FA levels would be associated with incident bleeding and AF events in MESA (Multi-Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline. Methods and Results We examined the association between baseline plasma n3-FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization International Classification of Diseases, Ninth Revision ( ICD-9 ), and International Classification of Diseases, Tenth Revision ( ICD-10 ), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3-FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1 years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA. Conclusions In MESA, higher plasma levels of n3-FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.

Background: Omega-3 (n-3) fatty acids have shown benefit in cognitively impaired subjects, but the effect on cognitively healthy older subjects is unclear., Objectives: Our aim was to determine if long-term, high-dose ω-3 ethyl esters, EPA (20:5n-3) and DHA (22:6n-3), prevent deterioration of cognitive function in cognitively healthy older adults., Methods: A total of 285 subjects with stable coronary artery disease (CAD) on statin treatment were randomly assigned to 3.36 g EPA and DHA or none (control) for 30 mo. Cognitive function was assessed in all 285 subjects at baseline and in 268 and 250 subjects who returned at 12- and 30-mo follow-up, respectively, with neuropsychological testing as a prespecified secondary outcome. A completer's analysis, along with a sensitivity analysis carrying forward the last observation, was performed., Results: Over the 30-mo period, subjects randomly assigned to EPA and DHA had significantly better scores than control for verbal fluency, language, and memory (mean: 1.08; 95% CI: 0.25, 1.91; P = 0.011) and 2 tests of visual-motor coordination (mean: -2.95; 95% CI: -5.33, -0.57; P = 0.015 and mean: -9.44; 95% CI: -18.60, -0.30; P = 0.043, respectively). The better scores for EPA and DHA were due to an improvement at 12 mo compared with baseline in verbal fluency, language, and memory (P = 0.047) and 2 tests of visual-motor coordination (P = 0.033 and P < 0.001, respectively), whereas control had no change. Post hoc analyses indicated no difference by age, sex, or diabetes status., Conclusions: Cognitively healthy older adults with stable CAD randomly assigned to high-dose EPA and DHA had improved cognitive function over a 30-mo period compared with control. These findings may be especially important for CAD patients because CAD is a risk factor for cognitive decline.This trial was registered at clinicaltrials.gov as NCT01624727., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Inflammation in arterial walls leads to coronary artery disease (CAD). We previously reported that a high omega-3 fatty index was associated with prevention of progression of coronary atherosclerosis, a disease of chronic inflammation in the arterial wall. However, the mechanism of such benefit is unclear. The two main omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors of specialized pro-resolving lipid mediators (SPMs)-resolvins and maresins-which actively resolve chronic inflammation. To explore whether SPMs are associated with coronary plaque progression, levels of SPMs and proinflammatory mediators (leukotriene B 4 [LTB 4 ] and prostaglandins) were measured using liquid chromatography-tandem mass spectrometry in 31 statin-treated patients with stable CAD randomized to either EPA and DHA, 3.36 g daily, or no EPA/DHA (control). Coronary plaque volume was measured by coronary computed tomographic angiography at baseline and at 30-month follow-up. Higher plasma levels of EPA+DHA were associated with significantly increased levels of two SPMs-resolvin E1 and maresin 1-and 18-hydroxy-eicosapentaenoic acid (HEPE), the precursor of resolvin E1. Those with low plasma EPA+DHA levels had a low (18-HEPE+resolvin E1)/LTB 4 ratio and significant plaque progression. Those with high plasma EPA+DHA levels had either low (18-HEPE+resolvin E1)/LTB 4 ratios with significant plaque progression or high (18-HEPE+resolvin E1)/LTB 4 ratios with significant plaque regression. These findings suggest that an imbalance between pro-resolving and proinflammatory lipid mediators is associated with plaque progression and potentially mediates the beneficial effects of EPA and DHA in CAD patients., (© 2021 Federation of American Societies for Experimental Biology.)

Obesity and diabetes are associated with chronic inflammation. Specialized pro-resolving lipid mediators (SPMs)-resolvins (Rv), protectins (PD) and maresins (MaR)-actively resolve inflammation. Bariatric surgery achieves remission of diabetes, but mechanisms are unclear. We measured SPMs and proinflammatory eicosanoid levels using liquid chromatography-tandem mass spectrometry in 29 morbidly obese subjects (13 with diabetes) and 15 nondiabetic, mildly obese subjects. Compared to the mildly obese, the morbidly obese had higher levels of SPMs-RvD3, RvD4 and PD1-and white blood cells (WBC) and platelets. Post-surgery, SPM and platelet levels decreased in morbidly obese nondiabetic subjects but not in diabetic subjects, suggesting continued inflammation. Despite similar weight reductions 1 year after surgery (44.6% vs. 46.6%), 8 diabetes remitters had significant reductions in WBC and platelet counts whereas five non-remitters did not. Remitters had a 58.2% decrease (p = 0.03) in 14-HDHA, a maresin pathway marker; non-remitters had an 875.7% increase in 14-HDHA but a 36.9% decrease in MaR1 to a median of 0. In conclusion, higher levels of RvD3, PD1 and their pathway marker, 17-HDHA, are markers of leukocyte activation and inflammation in morbid obesity and diabetes and diminish with weight loss in nondiabetic but not diabetic subjects, possibly representing sustained inflammation in the latter. Lack of diabetes remission after surgically-induced weight loss may be associated with reduced ability to produce MaR1 and sustained inflammation.

Purpose of Review: To provide an update on dietary measures to lower levels of LDL-C and triglyceride and reduce cardiovascular (CVD) outcomes., Recent Findings: Fifty-year follow-up in the Seven Countries Study confirmed that cholesterol levels correlate with saturated fat intake and all-cause mortality and age at death. In the PURE study, refined carbohydrate increased CVD risk whereas saturated fat did not despite increasing LDL-C levels; limitations are discussed. Reports on CVD risk with eggs provide conflicting results. Plant-based diets with healthful complex carbohydrates reduced CVD. The REDUCE-IT trial lowered triglyceride 21.6% and reduced CVD events 26.1% with an omega-3 fatty acid, An omega-3 fatty acid index at least 4% with EPA and docosahexaenoic acid prevented coronary plaque progression. A clinician guide to counsel patients on nutrition and heart healthy diets was recently published., Summary: Based on the evidence, individuals should continue to minimize saturated fats and refined carbohydrates, eliminate trans-fat and increase fruits, vegetables, whole grains, low-fat dairy, and fish or other omega-3 fatty acids. Adhering to a Mediterranean diet is strongly recommended because of lowering CVD and total mortality. High-dose omega-3 fatty acids lower triglyceride, reduce CVD and prevent coronary plaque progression.

The objective of our study was to characterize and analyze the associations between OSA (obstructive sleep apnea) and other clinical variables in adult patients referred for sleep evaluation by polysomnography at a referral center in Beirut, Lebanon, in terms of sociodemographic features, symptoms presentation and comorbidities, and evaluate the burden of comorbidities associated with this disease. All individuals with suspected Sleep Apnea referred (January 2010-September 2017) for a one-night polysomnography were included. Demographics, self-reported symptoms and comorbidities were documented. The relationship between OSA severity and the presence of symptoms and comorbidities were evaluated using multivariate logistic regression. Overall, 663 subjects were assessed. Of these, 57.3% were referred from chest physicians, and sleep test results were abnormal in 589 subjects (88.8%) of whom 526 patients (89.3%) fulfilled diagnostic criteria for OSA; 76.3% were men and women were on average older. OSA was severe in 43.2% and more severe in men. Almost all patients were symptomatic with ~2-4 symptoms per patient and women presented with symptoms that are more atypical. Comorbidities were significantly higher in women. In the multivariate analysis, age, male sex, obesity, symptoms of snoring, excessive daytime somnolence and witnessed apneas were associated with OSA severity. Only age and obesity were associated with self-reported diagnosis of hypertension and diabetes. This is the first study in Lebanon to explore the characteristics of patients with polysomnography-diagnosed OSA. High prevalence of severe OSA and low referral rates in the medical community support promoting awareness for an earlier diagnosis and more personalized approach in this country., Competing Interests: The research was funded by a grant from Philips. This does not alter our adherence to PLoS One policies on sharing data and materials.

Although cardiologists have long treated patients with coronary artery disease (CAD) and concomitant type 2 diabetes mellitus (T2DM), T2DM has traditionally been considered just a comorbidity that affected the development and progression of the disease. Over the past decade, a number of factors have shifted that have forced the cardiology community to reconsider the role of T2DM in CAD. First, in addition to being associated with increased cardiovascular risk, T2DM has the potential to affect a number of treatment choices for CAD. In this document, we discuss the role that T2DM has in the selection of testing for CAD, in medical management (both secondary prevention strategies and treatment of stable angina), and in the selection of revascularization strategy. Second, although glycemic control has been recommended as a part of comprehensive risk factor management in patients with CAD, there is mounting evidence that the mechanism by which glucose is managed can have a substantial impact on cardiovascular outcomes. In this document, we discuss the role of glycemic management (both in intensity of control and choice of medications) in cardiovascular outcomes. It is becoming clear that the cardiologist needs both to consider T2DM in cardiovascular treatment decisions and potentially to help guide the selection of glucose-lowering medications. Our statement provides a comprehensive summary of effective, patient-centered management of CAD in patients with T2DM, with emphasis on the emerging evidence. Given the increasing prevalence of T2DM and the accumulating evidence of the need to consider T2DM in treatment decisions, this knowledge will become ever more important to optimize our patients' cardiovascular outcomes.

Background Aerobic exercise capacity is inversely associated with cardiovascular and all-cause mortality in men and women without coronary artery disease (CAD); however, a higher amount of vigorous exercise is associated with a J-shaped relationship in CAD patients. Therefore, the optimal type and amount of exercise for CAD patients is unclear. Coronary artery calcification (CAC) is associated with increased cardiovascular disease (CVD) events and mortality. Fatty plaque is more likely to rupture and cause coronary events than other types. We examined the association between exercise capacity, fatty plaque, CAC score and CVD events in CAD patients. Methods and Results A total of 270 subjects with stable CAD were divided into tertiles based on metabolic equivalents of task (METs) calculated from exercise treadmill testing. Self-reported exercise was obtained. Coronary computed tomographic angiography measured coronary plaque volume and CAC score. After adjustment, fatty plaque volume was not different among the 3 MET groups. For each 1 MET increase, CAC was 66.2 units lower ( P =0.017). Those with CAC >400 and ≥8.2 METs had fewer CVD events over 30 months compared to <8.2 METs ( P =0.037). Of moderate intensity exercisers (median, 240 min/wk; 78% walking only), 62.4% achieved ≥8.2 METs and lower CAC scores ( P =0.07). Intensity and duration of exercise had no adverse impact on coronary plaque or CVD events. Conclusions Achieving ≥8.2 METs with moderate exercise intensity and volume as walking resulted in lower CAC scores and fewer CVD events. Therefore, vigorous exercise intensity and volume may not be needed for CAD patients to derive benefit. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01624727.

Purpose of Review: Several mutations in the apolipoprotein (apo) B, proprotein convertase subtilisin kexin 9 (PCSK9) and microsomal triglyceride transfer protein genes result in low or absent levels of apoB and LDL cholesterol (LDL-C) in plasma which cause familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL). Mutations in the angiopoietin-like protein 3 ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). Clinical manifestations range from none-to-severe, debilitating and life-threatening disorders. This review summarizes recent genetic, metabolic and clinical findings and management strategies., Recent Findings: Fatty liver, cirrhosis and hepatocellular carcinoma have been reported in FHBL and ABL probably due to decreased triglyceride export from the liver. Loss of function mutations in PCSK-9 and ANGPTL3 cause FHBL but not hepatic steatosis. In 12 case-control studies with 57 973 individuals, an apoB truncation was associated with a 72% reduction in coronary heart disease (odds ratio, 0.28; 95% confidence interval, 0.12-0.64; P = 0.002). PCSK9 inhibitors lowered risk of cardiovascular events in large, randomized trials without apparent adverse sequelae., Summary: Mutations causing low LDL-C and apoB have provided insight into lipid metabolism, disease associations and the basis for drug development to lower LDL-C in disorders causing high levels of cholesterol. Early diagnosis and treatment is necessary to prevent adverse sequelae from FHBL and ABL.

The Middle East and North Africa regions, including Lebanon, have recently witnessed rapid urbanization and modernization over the last couple of decades that has led to a dramatic transformation affecting lifestyle and diet. The World Health Organization reports that the leading cause of death in Lebanon is due to cardiovascular disease (CVD) at 47% of all-cause mortality. Over the last 30 years, especially the last 10, the population of Lebanon has changed dramatically due to the effect of wars in the region and refugees seeking asylum. With a population of around 4.5 million and a relatively high rate of consanguinity in Lebanon, a variety of novel mutations have been discovered explaining several familial causes of hypercholesterolemia, diabetes mellitus, congenital heart disease, and cardiomyopathies. Due to the Syrian civil war, 1.5 million Syrian refugees now reside in Lebanon in either low-income housing or tented settlements. A National Institutes of Health study is examining diabetes and CVD in Syrian refugees in comparison to native Lebanese. We provide the first review of CVD in Lebanon in its metabolic component including coronary artery disease and its risk factors, mainly hyperlipidemia and diabetes mellitus, and its structural component, including congenital heart disease, valvular heart disease, cardiomyopathies, and heart failure. The knowledge in this review has been compiled to guide clinicians and assist researchers in efforts to recognize risk factors for disease, improve delivery of health care, and prevent and treat CVDs in Lebanon, both for the native Lebanese and Syrian refugees.

Background: Studies of sex-based differences in older adults with acute myocardial infarction (AMI) have yielded mixed results. We, therefore, sought to evaluate sex-based differences in presentation characteristics, treatments, functional impairments, and in-hospital complications in a large, well-characterized population of older adults (≥75 years) hospitalized with AMI., Methods and Results: We analyzed data from participants enrolled in SILVER-AMI (Comprehensive Evaluation of Risk Factors in Older Patients With Acute Myocardial Infarction)-a prospective observational study consisting of 3041 older patients (44% women) hospitalized for AMI. Participants were stratified by AMI subtype (ST-segment-elevation myocardial infarction [STEMI] and non-STEMI [NSTEMI]) and subsequently evaluated for sex-based differences in clinical presentation, functional impairments, management, and in-hospital complications. Among the study sample, women were slightly older than men (NSTEMI: 82.1 versus 81.3, P <0.001; STEMI: 82.2 versus 80.6, P <0.001) and had lower rates of prior coronary disease. Women in the NSTEMI subgroup presented less frequently with chest pain as their primary symptom. Age-associated functional impairments at baseline were more common in women in both AMI subgroups (cognitive impairment, NSTEMI: 20.6% versus 14.3%, P <0.001; STEMI: 20.6% versus 12.4%, P =0.001; activities of daily living disability, NSTEMI: 19.7% versus 11.4%, P <0.001; STEMI: 14.8% versus 6.4%, P <0.001; impaired functional mobility, NSTEMI: 44.5% versus 30.7%, P <0.001; STEMI: 39.4% versus 22.0%, P <0.001). Women with AMI had lower rates of obstructive coronary disease (NSTEMI: P <0.001; STEMI: P =0.02), driven by lower rates of 3-vessel or left main disease than men (STEMI: 38.8% versus 58.7%; STEMI: 24.3% versus 32.1%), and underwent revascularization less commonly (NSTEMI: 55.6% versus 63.6%, P <0.001; STEMI: 87.3% versus 93.3%, P =0.01). Rates of bleeding were higher among women with STEMI (26.2% versus 15.6%, P <0.001) but not NSTEMI (17.8% versus 15.7%, P =0.21). Women had a higher frequency of bleeding following percutaneous coronary intervention with both NSTEMI (11.0% versus 7.8%, P =0.04) and STEMI (22.6% versus 14.8%, P =0.02)., Conclusions: Among older adults hospitalized with AMI, women had a higher prevalence of age-related functional impairments and, among the STEMI subgroup, a higher incidence of overall bleeding events, which was driven by higher rates of nonmajor bleeding events and bleeding following percutaneous coronary intervention. These differences may have important implications for in-hospital and posthospitalization needs.

Hypertriglyceridemia (triglycerides 200-499 mg/dL) is relatively common in the United States, whereas more severe triglyceride elevations (very high triglycerides, ≥500 mg/dL) are far less frequently observed. Both are becoming increasingly prevalent in the United States and elsewhere, likely driven in large part by growing rates of obesity and diabetes mellitus. In a 2002 American Heart Association scientific statement, the omega-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were recommended (at a dose of 2-4 g/d) for reducing triglycerides in patients with elevated triglycerides. Since 2002, prescription agents containing EPA+DHA or EPA alone have been approved by the US Food and Drug Administration for treating very high triglycerides; these agents are also widely used for hypertriglyceridemia. The purpose of this advisory is to summarize the lipid and lipoprotein effects resulting from pharmacological doses of n-3 FAs (>3 g/d total EPA+DHA) on the basis of new scientific data and availability of n-3 FA agents. In treatment of very high triglycerides with 4 g/d, EPA+DHA agents reduce triglycerides by ≥30% with concurrent increases in low-density lipoprotein cholesterol, whereas EPA-only did not raise low-density lipoprotein cholesterol in very high triglycerides. When used to treat hypertriglyceridemia, n-3 FAs with EPA+DHA or with EPA-only appear roughly comparable for triglyceride lowering and do not increase low-density lipoprotein cholesterol when used as monotherapy or in combination with a statin. In the largest trials of 4 g/d prescription n-3 FA, non-high-density lipoprotein cholesterol and apolipoprotein B were modestly decreased, indicating reductions in total atherogenic lipoproteins. The use of n-3 FA (4 g/d) for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With EPA Intervention Trial), a randomized placebo-controlled trial of EPA-only in high-risk patients treated with a statin. The results of a trial of 4 g/d prescription EPA+DHA in hypertriglyceridemia are anticipated in 2020. We conclude that prescription n-3 FAs (EPA+DHA or EPA-only) at a dose of 4 g/d (>3 g/d total EPA+DHA) are an effective and safe option for reducing triglycerides as monotherapy or as an adjunct to other lipid-lowering agents.

Despite continued advances in health care, the cardiovascular disease (CVD) mortality rate has plateaued in recent years and appears to be trending upward. Poor diet is a leading cause of obesity and type 2 diabetes mellitus, which are leading contributors to CVD morbidity and mortality. Although dietary modification is a cornerstone of CVD prevention, implementation in clinical practice is limited by inadequate formal training in nutrition science. In this report, we review the individual components of a heart-healthy diet, evidence-based dietary recommendations, and the impact of diet on CVD risk factor prevention and management. Furthermore, we examine the unique difficulties of dietary counseling in low-socioeconomic-status environments and provide an evidence-based approach to better serve these populations. We utilized PubMed searches in adults with no date restriction with the following search terms: "carbohydrate," "fat," protein," "DASH," "Mediterranean," "plant-based," "vegetarian," "cardiovascular disease," "obesity," "weight loss," "diabetes," "socioeconomic status," and "race." In this review, we demonstrate that patients should focus on implementing a general diet plan that is high in fruits, whole grains, legumes, and nonstarchy vegetables while low in trans -fats, saturated fats, sodium, red meat, refined carbohydrates, and sugar-sweetened beverages. The Dietary Approaches to Stop Hypertension, Mediterranean, and vegetarian diets have the most evidence for CVD prevention. Clinicians should understand the barriers that patients may face in terms of access to healthy dietary choices. Further research is needed to determine the dietary changes that are most economically, socioculturally, and logistically feasible to reduce these barriers. Improvement in diet is a public health priority that can lead to a significant population-level reduction in CVD morbidity and mortality. It is imperative that clinicians understand current dietary practice guidelines and implement evidence-based dietary counseling in those at high risk for CVD.

Background and Aims: Higher blood levels of the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been associated with fewer cardiovascular events and lower mortality in prospective studies. Our aim was to determine a target level of EPA and DHA to prevent progression of coronary artery plaque., Methods: 218 subjects with stable coronary artery disease on statins were randomized to high-dose EPA and DHA (3.36 g daily) or no omega-3 for 30 months. Coronary plaque volume was measured by coronary computed tomographic angiography. Plasma phospholipid levels of EPA, DHA and total fatty acids were measured by gas chromatography mass spectrometry. The omega-3 fatty acid index was calculated as EPA+DHA/total fatty acid., Results: Mean (SD) age was 62.9 (7.8) years; mean (SD) LDL-C level 78.6 (27.3) mg/dL and median triglyceride level 122 mg/dL. Subjects assigned to EPA and DHA had increased plasma EPA and DHA levels variably from 1.85% to 13.02%. Plasma omega-3 fatty acid index ≥4% prevented progression of fibrous, noncalcified, calcified and total plaque in nondiabetic subjects whereas those in the lowest quartile (<3.43%) had significant progression of fibrous, calcified and total plaque. No difference was observed in diabetic subjects., Conclusions: EPA and DHA added to statins prevented coronary plaque progression in nondiabetic subjects with mean LDL-C <80 mg/dL, when an omega-3 index ≥4% was achieved. Low omega-3 index <3.43% identified nondiabetic subjects at risk of coronary plaque progression despite statin therapy. These findings highlight the importance of measuring plasma levels of omega-3 fatty acids early and at trial conclusion. Targeting an omega-3 index ≥4% maximizes cardiovascular benefit., (Copyright © 2019 Elsevier B.V. All rights reserved.)

One in 4 Americans >40 years of age takes a statin to reduce the risk of myocardial infarction, ischemic stroke, and other complications of atherosclerotic disease. The most effective statins produce a mean reduction in low-density lipoprotein cholesterol of 55% to 60% at the maximum dosage, and 6 of the 7 marketed statins are available in generic form, which makes them affordable for most patients. Primarily using data from randomized controlled trials, supplemented with observational data where necessary, this scientific statement provides a comprehensive review of statin safety and tolerability. The review covers the general patient population, as well as demographic subgroups, including the elderly, children, pregnant women, East Asians, and patients with specific conditions such as chronic disease of the kidney and liver, human immunodeficiency viral infection, and organ transplants. The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%, and the risk of serious hepatotoxicity is ≈0.001%. The risk of statin-induced newly diagnosed diabetes mellitus is ≈0.2% per year of treatment, depending on the underlying risk of diabetes mellitus in the population studied. In patients with cerebrovascular disease, statins possibly increase the risk of hemorrhagic stroke; however, they clearly produce a greater reduction in the risk of atherothrombotic stroke and thus total stroke, as well as other cardiovascular events. There is no convincing evidence for a causal relationship between statins and cancer, cataracts, cognitive dysfunction, peripheral neuropathy, erectile dysfunction, or tendonitis. In US clinical practices, roughly 10% of patients stop taking a statin because of subjective complaints, most commonly muscle symptoms without raised creatine kinase. In contrast, in randomized clinical trials, the difference in the incidence of muscle symptoms without significantly raised creatinine kinase in statin-treated compared with placebo-treated participants is <1%, and it is even smaller (0.1%) for patients who discontinued treatment because of such muscle symptoms. This suggests that muscle symptoms are usually not caused by pharmacological effects of the statin. Restarting statin therapy in these patients can be challenging, but it is important, especially in patients at high risk of cardiovascular events, for whom prevention of these events is a priority. Overall, in patients for whom statin treatment is recommended by current guidelines, the benefits greatly outweigh the risks.

Purpose of Review: Summarize studies on omega-3 fatty acids in prevention of albuminuria in subjects with diabetes., Recent Findings: Several small, short-term trials suggested benefit on albuminuria in subjects with diabetes; however, results were not definitive. Welty et al. showed that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 1 year slowed progression of early-stage albuminuria in subjects with diabetes with clinical coronary artery disease on an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, the majority of whom had an albumin/creatinine ratio (ACR) < 30 μg/mg. Moreover, significantly more (3-fold) subjects on EPA and DHA had a decrease in ACR compared to control, and three on EPA and DHA had a change in category from > 30 μg/mg to < 30 μg/mg, whereas no controls did. Potential mechanisms for benefit are discussed. These results suggest that there is benefit and perhaps even reversal of albuminuria with EPA and DHA at an early stage of disease in those with ACR < 30 μg/mg and those with microalbuminuria (ACR > 30).

Background and Aims: Hypertension is associated with increased clinical and subclinical coronary artery disease (CAD); however, the relationship between blood pressure and coronary plaque volume is unclear. We examined the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on coronary artery plaque volume., Methods: 285 subjects with stable CAD on statin therapy underwent coronary computed tomographic angiography to measure volume of fatty, fibrous, noncalcified, calcified and total coronary plaque., Results: Mean (SD) age was 63.1 (7.7); mean (SD) LDL-C, 78.7 mg/dL (28.5). Compared to the highest DBP tertile (>76 mmHg), those in the lowest DBP tertile (≤68 mmHg) had lower volumes of fatty: 10.0 vs. 7.7 mm 3 /mm, (p trend = 0.042), fibrous: 19.6 vs. 13.8 mm 3 /mm (p trend = 0.011), non-calcified: 29.7 vs. 22.5 mm 3 /mm (p trend = 0.017) and total plaque: 37.8 vs. 25.1 mm 3 /mm (p trend = 0.010) whereas there was no relationship with SBP tertiles. Similarly, when examined as a continuous variable, higher DBP was a significant independent predictor of higher plaque volume after multivariate adjustment: for every 1 mmHg increase in DBP, fibrous plaque increased 0.128 mm 3 /mm (p = 0.022), noncalcified plaque increased 0.176 mm 3 /mm (p = 0.045), calcified plaque increased 0.096 mm 3 /mm (p = 0.001) and total plaque increased 0.249 mm 3 /mm (p = 0.019) whereas SBP ranging from 95 to 154 mmHg did not predict plaque volume., Conclusions: Level of DBP predicts coronary plaque with a DBP tertile ≤68 mmHg associated with the least amount of coronary plaque in subjects with LDL-C < 80 mg/dL., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Poor physical function impairs fitness and exercise and is associated with worse cardiovascular outcomes and all-cause mortality. Joint pain and stiffness limit physical function., Objective: To determine if eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation improves physical function and exercise in coronary artery disease (CAD) patients., Methods: A total of 291 subjects with stable CAD were randomized to either Lovaza (1.86 g of EPA and 1.5 g of DHA daily) or no Lovaza (control) for 1 year. Change in pain, stiffness, and physical function was assessed by the Western Ontario and McMaster Universities Arthritis Index. Minutes of exercise per week were recorded, and musculoskeletal events were reported., Results: Mean age (standard deviation) was 63.3 (7.6) years. In the intention-to-treat analysis, compared with controls, those on Lovaza had better physical function (mean difference, -11.0%, 95% confidence interval [CI] -18.5% to -3.5%, P = .004), better total Western Ontario and McMaster Universities Arthritis Index scores (mean difference, -9.8%, 95% CI -16.6% to -3.0%, P = .005), more exercise per week (135 minutes vs 197 minutes, respectively, P = .028), and less joint replacement (11 vs 1, respectively, P = .002). Pain and stiffness showed a trend toward significance (P = .06). The per-protocol analysis also showed less stiffness compared with controls (mean difference, -11.5%, 95% CI -22.9% to -0.1%, P = .048)., Conclusion: High-dose EPA and DHA may benefit CAD patients by preserving physical function, increasing amount of exercise, and reducing joint replacement. EPA and DHA may be a safe preventative strategy against musculoskeletal symptoms in CAD patients., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Although statins reduce cardiovascular events, residual risk remains. Therefore, additional modalities are needed to reduce risk. We evaluated the effect of eicosapentaenoic acid and docosahexaenoic acid in pharmacologic doses added to statin treatment on coronary artery plaque volume., Methods and Results: A total of 285 subjects with stable coronary artery disease on statins were randomized to omega-3 ethyl-ester (1.86 g of eicosapentaenoic acid and 1.5 g of docosahexaenoic acid daily) or no omega-3 (control) for 30 months. Coronary plaque volume was assessed by coronary computed tomographic angiography. Mean (SD) age was 63.0 (7.7) years; mean low-density lipoprotein cholesterol ≤80 mg/dL. In the intention-to-treat analysis, our primary endpoint, noncalcified plaque volume, was not different between groups ( P =0.14) but approached significance in the per protocol analysis ( P =0.07). When stratified by age in the intention-to-treat analysis, younger omega-3 subjects had significantly less progression of the primary endpoint, noncalcified plaque ( P =0.013), and fibrous, calcified and total plaque. In plaque subtype analysis, controls had significant progression of fibrous plaque compared to no change in the omega-3 ethyl-ester group (median % change [interquartile range], 5.0% [-5.7, 20.0] versus -0.1% [-12.3, 14.5], respectively; P =0.018). Among those on low-intensity statins, omega-3 ethyl-ester subjects had attenuation of fibrous plaque progression compared to controls (median % change [interquartile range], 0.3% [-12.8, 9.0] versus 4.8% [-5.1, 19.0], respectively; P =0.032). In contrast, those on high-intensity statins had no difference in plaque change in either treatment arm., Conclusions: High-dose eicosapentaenoic acid and docosahexaenoic acid provided additional benefit to statins in preventing progression of fibrous coronary plaque in subjects adherent to therapy with well-controlled low-density lipoprotein cholesterol levels. The benefit on low-intensity statin, but not high-intensity statin, suggests that statin intensity affects plaque volume., Clinical Trial Registration: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01624727., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Albuminuria is a marker of inflammation and an independent predictor of cardiovascular morbidity and mortality. The current study evaluated whether eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation attenuates progression of albuminuria in subjects with coronary artery disease., Methods and Results: Two-hundred sixty-two subjects with stable coronary artery disease were randomized to either Lovaza (1.86 g of EPA and 1.5 g of DHA daily) or no Lovaza (control) for 1 year. Percent change in urine albumin-to-creatinine ratio (ACR) was compared. Mean (SD) age was 63.3 (7.6) years; 17% were women and 30% had type 2 diabetes mellitus. In nondiabetic subjects, no change in urine ACR occurred in either the Lovaza or control groups. In contrast, ACR increased 72.3% ( P <0.001) in diabetic subjects not receiving Lovaza, whereas those receiving Lovaza had no change. In diabetic subjects on an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker, those receiving Lovaza had no change in urine ACR, whereas those not receiving Lovaza had a 64.2% increase ( P <0.001). Change in ACR was directly correlated with change in systolic blood pressure ( r =0.394, P =0.01)., Conclusions: EPA and DHA supplementation attenuated progression of albuminuria in subjects with type 2 diabetes mellitus and coronary artery disease, most of whom were on an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker. Thus, EPA and DHA supplementation should be considered as additional therapy to an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker in subjects with type 2 diabetes mellitus and coronary artery disease., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01624727., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Aims: Prior data on the association between parity and mortality are limited by the presence of sociodemographic confounders including cultural norms of parity. Our objective was to determine the association between parity and mortality in the Amish, a socioeconomically homogenous group with large numbers of children per family., Methods: We conducted a population-based cohort study among 518 Old Order Amish women enrolled in a cardiovascular awareness program. The mean length of follow-up for mortality was 13.52 years. We determined the adjusted associations between parity and obesity, prevalent coronary heart disease and mortality., Results: The mean number of total births per woman was 6.7 ± 3.6 with a mode of 8. No significant association was observed between parity and all-cause mortality when adjusted for age (HR 1.00 per additional birth; 95% CI 0.96-1.05; p = 0.85) or in multivariate analysis (HR 1.00, 95% CI 0.95-1.05; p = 0.95). There was also no association of parity in age- or multivariable adjusted models with prevalent diabetes, hypertension or coronary heart disease. Despite the lack of effect of parity on mortality, a significant association of ten or more births was observed with higher body mass index (BMI) compared to the referent group of 8-9 total births., Conclusions: In a highly homogeneous population with high rates of parity, no association between overall mortality and parity was observed. Ten or more births were significantly associated with a higher BMI but not with overall mortality., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)