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Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

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.

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.

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.

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.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.Mean ± SD age was 62.1 ± 10.2 years and 52.9% were females. The median follow-up time was 15.6 years. Higher logIn 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.

Introduction: Higher coronary artery calcium (CAC) scores have been associated with increased cardiovascular (CVD) events and mortality. Women develop coronary artery disease (CAD) on average 10-15 years older than men and have worse outcomes than men when CVD events occur. The effect of exercise capacity on CAC scores in women with CAD is unclear. Objective: To determine if exercise capacity is predictive of CAC scores in men and women with CAD. Methods: A total of 203 men and 38 women with known CAD had CAC scores measured using noncontrast multidetector coronary tomography. All subjects underwent maximal exercise treadmill testing with calculation of metabolic equivalents of task (METs) achieved as a measure of cardiorespiratory fitness. Results: Mean (SD) age was not different in men and women: 62.7 (7.9) and 64.4 (6.8) years, P=0.239, respectively. CAC scores were significantly lower in women compared to men: median [IQR]: 114.0 [27.5, 321.0] Agatston units vs 535.3 [182.9, 1367.4] respectively, (P Conclusions: Despite having known CAD, female CAC scores did not equal those of men until women were 20 years older. The independent association of METs with CAC score in women supports counseling women to exercise to maximize their cardiorespiratory fitness to minimize CAC scores. Since higher CAC scores predict adverse CVD events and mortality, lower CAC scores should protect women from development of CVD events and possibly lower their worse outcome.

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.

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.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.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.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.

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 highdose 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 (

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.

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 B4 [LTB4 ] 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)/LTB4 ratio and significant plaque progression. Those with high plasma EPA+DHA levels had either low (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque progression or high (18-HEPE+resolvin E1)/LTB4 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.

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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01624727

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.

Introduction: Statins have led to significant reductions in cardiovascular disease (CVD) events; however, a high level of residual cardiovascular risk remains. The REDUCE-IT trial showed additional benefit with icosapent ethyl to statins in reducing CVD morbidity and mortality. However, the safety of omega-3 ethyl esters with regards to atrial fibrillation (Afib) in patients with coronary artery disease (CAD) remains unclear. Hypothesis: We hypothesize that omega-3 ethyl esters may influence the risk of Afib or flutter in patients with CAD. Methods: In total, 285 CAD patients on statins were randomized to high dose omega-3 ethyl esters (1.86 g of Eicosapentaenoic acid [EPA] and 1.5 g of Docosahexaenoic acid [DHA]) or no omega-3 for 30 months. The incidence and recurrence of Afib or flutter was compared in those on EPA/DHA plus statin to statin alone (control). Results: A total of 240 patients were included in the analysis and no difference in baseline characteristics was observed (Table A). In total, 19 patients were in Afib or flutter during the trial: 12 in EPA/DHA and 7 in control (9.5% vs. 6.1%, respectively, p=0.33). The incidence of new onset Afib or flutter within 30 months was 7.2% and 4.9% in patients receiving omega-3 ethyl esters compared to controls, respectively (p=0.48). No significant difference in recurrence of Afib occurred among patients with a history of paroxysmal Afib receiving omega-3 ethyl esters compared to control (26.7% vs. 16.7%, respectively, p=0.53) (Table B). Conclusions: EPA/DHA did not increase the incidence of Afib or flutter in patients with established CAD. Further studies are warranted to better understand the effects of omega-3 ethyl esters on the cardiac conduction system.

Introduction: The association between plasma OM3 FA levels and key safety endpoints identified in the REDUCE-IT trial such as bleeding and atrial fibrillation (AF) remains uncertain. Hypothesis: Consistent with REDUCE-IT, we hypothesized that higher baseline OM3 FA levels, particularly EPA, would be associated with incident bleeding and AF in a population free of clinical ASCVD or AF. Methods: We examined the association between baseline plasma OM3 FA levels (expressed as percent mass of total FA) with incident bleeding and AF in MESA. Bleeding events were identified from review of hospitalization ICD-9/10 codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Multivariable Cox proportional hazard modeling was used to estimate HRs of the association of continuous OM3 FA (log EPA, log DHA, log (EPA+DHA)) and our outcomes. Results: Among the 6546 participants, mean age was 62.1(±10.2) and 3468(53%) were female. For incident bleeding, consistent statistically significant reductions were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk, such as aspirin, NSAIDS, corticosteroids and proton pump inhibitors (Table). For incident AF, a significant reduction was seen with increasing levels of DHA in univariate analyses that did not persist following adjustment for AF risk factors. No significant associations were seen with either EPA or EPA+DHA. Conclusions: In MESA, a population free of clinical ASCVD or AF at baseline, higher plasma levels of OM3 FA (EPA and EPA+DHA, but not DHA) were associated with significantly lower risk of hospitalized bleeding events, but there was no significant association with AF. These findings from observational studies will need to be reconciled with clinical trial data of high-dose pharmacologic OM3 FA therapy.

Background: In REDUCE-IT, high-dose eicosapentaenoic acid (EPA) was beneficial in high-risk patients without clinical CVD independent of triglyceride levels. Whether the benefit of higher plasma EPA extends to those without subclinical CVD is unclear. Hypothesis: In those without clinical CVD, plasma omega-3 fatty acid (O3FA) levels predict long-term CVD events, and subclinical CVD measured by coronary artery calcium (CAC) modifies the effect such that individuals with the highest CAC attain the greatest benefit from higher O3FA. Methods: We examined 6568 MESA participants with plasma EPA and docosahexaenoic acid (DHA) levels measured at baseline and classified them by tertiles of EPA and DHA and by CAC category (0, 1-99, ≥100). Our outcome was time to CVD event (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Cox regression models were used to assess the associations between log-transformed EPA and DHA and CVD events adjusted for demographic factors, CVD risk factors, and medication use. Results: Mean age was 62.1±10.2 and 52.9% were females. Higher log(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.93; P = 0.002) and log(DHA) (aHR = 0.80; 95% CI, 0.66-0.96; P = 0.019) were independently associated with fewer CVD events. The difference in absolute CVD event rates between the lowest and highest EPA tertile increased at higher CAC levels (Figure). The adjusted HR for highest compared to lowest EPA tertile within CAC 0 was 1.02 (95% CI, 0.72-1.45), CAC 1-99 was 0.71 (95% CI, 0.51-0.98), and CAC≥100 was 0.66 (95% CI, 0.52-0.83). A similar association was seen in tertiles of DHA by CAC category. These findings were consistent by sex and race category and after adjusting for O3FA supplement use. Conclusion: In an ethnically diverse population free of clinical CVD at baseline, higher plasma O3FA levels were associated with fewer CVD events. The absolute reduction in CVD events with higher O3FA levels was more apparent at higher CAC scores.

Introduction: Epicardial adipose tissue is an ectopic fat depot that may be associated with coronary artery atherosclerosis. Reduction in weight has been associated with a reduction in epicardial fat volume in several studies. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are known to lower triglyceride level. Whether the reduction in triglyceride level is associated with a reduction in epicardial fat volume is unknown. Hypothesis: We hypothesize that EPA and DHA reduce triglyceride levels and possibly can cause regression of epicardial fat volume after 30 months of therapy. Methods: A total of 139 patients with stable coronary artery disease on statins were randomized to EPA and DHA versus none for 30 months. Epicardial fat volume was measured with coronary computed tomographic angiography at baseline and 30 months. Change in epicardial fat volume was calculated. Results: No difference in baseline characteristics was observed (Table). At 30-month follow-up, those on EPA and DHA had a significant 6.7% reduction in triglyceride level compared to a 12.6% increase in controls (p=0.02). However, there was no difference in percent change in epicardial fat volume between control and EPA/DHA groups at 30 months (-3.1% [-16.7, 4.9] vs. -5.0% [-13.1,7.3], p-value=0.80, respectively). There was no significant change in body mass index in either group at 30-month follow-up. Conclusions: EPA and DHA led to a significant reduction of triglyceride level; however, there was no corresponding significant reduction in epicardial fat volume. This finding suggests that lowering triglyceride level does not affect epicardial fat volume.

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.

Background: Statin-treated patients with diabetes mellitus (DM) are at high cardiovascular (CV) risk. Methods: In REDUCE-IT, icosapent ethyl (IPE; 4 g/day) reduced CV risk vs. placebo in statin-treated patients with either DM plus risk factors or established CV disease. The primary endpoint was CV death, myocardial infarction (MI), stroke, coronary revascularization, or unstable angina. The key secondary endpoint was CV death, MI, or stroke. Key DM analyses were prespecified. Results: 58.5% of patients had DM; 91.0% on ≥1 DM medication, 49.5% on ≥2. IPE reduced primary (Figure) and key secondary first and total (first plus recurrent) events. Patients with and without DM both showed substantial benefits, but patients with DM had 1.5-fold greater rates of the primary endpoint in the placebo group, and a 7% absolute risk reduction in first and a 12.7% reduction in total events (both p Conclusion: IPE 4 g/day provides robust CV benefits in statin-treated patients with DM, with large relative and absolute risk reductions in both first and total CV events. Disclosure D.L. Bhatt: Research Support; Self; Abbott, Afimmune, Amarin Corporation, Amgen, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Cardax, Chiesi USA, Inc., CSL Behring, Ferring Pharmaceuticals, Fractyl Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Ischemix, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis, Synaptic. E.A. Brinton: Consultant; Self; Esperion Therapeutics, Inc., Medicines Company, Regeneron Pharmaceuticals. Speaker’s Bureau; Self; Amarin Corporation, Amgen, Esperion Therapeutics, Inc. Other Relationship; Self; Amarin Corporation, Kowa Pharmaceuticals America, Inc. M. Miller: Consultant; Self; Amarin Corporation. P.G. Steg: Consultant; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Idorsia, Mylan, Novartis AG, Pfizer Inc., Sanofi, Servier. Research Support; Self; Amarin Corporation. Speaker’s Bureau; Self; Novo Nordisk A/S. T.A. Jacobson: Consultant; Self; Esperion Therapeutics, Inc., Regeneron Pharmaceuticals, Sanofi US. Other Relationship; Self; Amarin Corporation. S.B. Ketchum: Other Relationship; Self; Amarin Corporation. R.T. Doyle: Other Relationship; Self; Amarin Corporation. R.A. Juliano: Other Relationship; Self; Amarin Corporation. L. Jiao: Other Relationship; Self; Amarin Corporation. C. Granowitz: Other Relationship; Self; Amarin Corporation. O. Ganda: Consultant; Self; Amarin Corporation. Other Relationship; Self; Novo Nordisk A/S. F.K. Welty: Other Relationship; Self; Boehringer Ingelheim International GmbH. R.S. Busch: Research Support; Self; Amarin Corporation, Bayer AG, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc. Speaker’s Bureau; Self; Amarin Corporation, Amgen, Esperion Therapeutics, Inc., Novo Nordisk Inc., Sanofi US. A.C. Goldberg: Advisory Panel; Self; Akcea Therapeutics, Esperion Therapeutics, Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Sanofi-Aventis. Research Support; Self; Akcea Therapeutics, Amarin Corporation, Amgen, Ionis Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Regeneron Pharmaceuticals, Sanofi-Aventis. Other Relationship; Self; Merck & Co., Inc. D.M. Herrington: None. M. Budoff: Research Support; Self; Amarin Corporation, General Electric. Speaker’s Bureau; Self; Amarin Corporation. J. Tardif: Research Support; Self; Esperion Therapeutics, Inc., Ionis Pharmaceuticals, Inc., REGENXBIO Inc., Sanofi, Servier. Other Relationship; Self; Amarin Corporation, AstraZeneca, DalCor Pharmaceuticals. C.M. Ballantyne: Consultant; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen, Arrowhead Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Corvidia, Denka-Seiken Co., Ltd., Esperion Therapeutics, Inc., Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Matinas BioPharma, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Research Support; Self; Abbott, Akcea Therapeutics, Amgen, Esperion Therapeutics, Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Roche Diagnostic USA. Funding Amarin Pharma Inc

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

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 ( MET s) 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 MET s had fewer CVD events over 30 months compared to MET s ( P =0.037). Of moderate intensity exercisers (median, 240 min/wk; 78% walking only), 62.4% achieved ≥8.2 MET s 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 MET s 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: NCT 01624727.

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.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.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 role of proprotein convertase subtilisin/kexin type 9 (PCSK9) recently emerged as a crucial component in lipid homeostasis after extensive investigational efforts conducted to unveil the complex mechanisms associated with familial hypercholesterolemia. In 2003, Abifadel et al. were the first to identify mutations in the genes encoding for PCSK9 as a cause of autosomal familial hypercholesterolemia (FH) [1]. Investigating the role of PCSK9 showed its association with low-density lipoprotein (LDL) receptor intracellular degradation [2-5]. The relationship between LDL-cholesterol (LDL-C) serum levels and atherosclerosis has been extensively studied. Higher LDL-C levels are strongly correlated with atherosclerosis and higher cardiovascular comorbidities and mortality [6]. Whereas gain-of-function mutations was associated with increased levels of LDL-C and early onset of atherosclerosis [7], loss-of-function mutations on the other hand was linked to a lower LDL-C and a subsequent decrease in cardiovascular risk [8, 9]. This prompted evaluation of the therapeutic potential of inhibiting PCSK9, where a monoclonal antibody inhibiting PCSK9, when added to conventional therapy (statins), was found to further reduce the incidence of cardiovascular events in the Open Label Study of Long Term Evaluation against LDL-C (OSLER) trials [10], as well as reduce mortality and improve outcomes in the recently published “Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk” (FOURIER) trial [11]. Regarding its physiology, the PCSK9 protein is expressed in significant amounts in the liver, intestine and the kidneys [12]. In addition to its role in lipid metabolism, PCSK9 is also expressed in pancreatic insulin-secreting beta cells and has been shown to play a part in normal insulin homeostasis [13]. Besides, the role of PCSK9 extends to involve regulation of inflammation, blood pressure and carcinogenesis [14-16]. This non-systematic review summarizes the data present to date and pertaining to the emerging role of PCSK9 in the different aspect of cardiovascular homeostasis focusing on dyslipidemia, glomerular proteinuria, insulin secretion, blood pressure regulation and inflammation. In order to compile a comprehensive data for this review, PubMed, EMBASE, Scholar and Scopus databases were searched to identify randomized controlled trials, observational studies, in-vitro trials and reviews about the role of PCSK9 in cardiovascular homeostasis.

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,PPPP=0.001; activities of daily living disability, NSTEMI: 19.7% versus 11.4%,PPPPPP=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%,PP=0.01). Rates of bleeding were higher among women with STEMI (26.2% versus 15.6%,PP=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.

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

Lipoprotein(a) [Lp(a)] is an apolipoprotein(a) molecule bound to 1 apolipoprotein B-100. Elevated levels of Lp(a) are thought to be an independent risk factor for atherosclerosis and to promote thrombosis through incompletely understood mechanisms. We report a 34-year-old man with an ischemic stroke in the setting of an extremely high Lp(a) level-212 mg/dL. He developed severe carotid artery stenosis over a 6-year period and had thrombus formation post-carotid endarterectomy. To our knowledge, this case is unique because the Lp(a) is the highest reported level in a patient without renal disease. Moreover, this is the first reported case of the youngest individual with a stroke presumably related to development of carotid plaque over a 6-year period. The thrombotic complication after endarterectomy may have been related to the prothrombotic properties of Lp(a). Of note, the Lp(a) level did not respond to atorvastatin but did decrease 15% after aspirin 325 mg was added although his Lp(a) levels were variable, and it is not clear that this was cause and effect. This case highlights the need to better understand the relation between Lp(a) and vascular disease and the need to screen family members for elevated Lp(a). We also review treatment options to lower Lp(a) and ongoing clinical trials of newer lipid-lowering drugs that can also lower Lp(a).

Summarize studies on omega-3 fatty acids in prevention of albuminuria in subjects with diabetes.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).