Improving lipids with prescription icosapent ethyl after previous use of fish oil dietary supplements.

Managing dyslipidemia can be challenging in patients with statin intolerance. We describe the lipid effects of icosapent ethyl 4 g/day (high-purity prescription omega-3 eicosapentaenoic acid) in two coronary artery disease patients with statin intolerance who were self-treating with fish oil dietary supplements. After initiating icosapent ethyl, improvements were noted in the first and second patients, respectively, in total cholesterol (-12%; -21%), LDL cholesterol (-3%; -24%), triglycerides (-34%; -16%), non-HDL cholesterol (-12%; -22%), the omega-3 index (+42%; +8%) and eicosapentaenoic acid levels (+275%; +138%). Icosapent ethyl was well tolerated with no adverse events reported. These cases demonstrated favorable lipid effects with prescription icosapent ethyl treatment that may help optimize the care of high-risk coronary artery disease patients with statin intolerance.

Aortic valve regurgitation that resolved after a ruptured coronary sinus aneurysm was patched.

Sinus of Valsalva aneurysms appear to be rare. They occur most frequently in the right sinus of Valsalva (52%) and the noncoronary sinus (33%). More of these aneurysms originate from the right coronary cusp than from the noncoronary cusp. Surgical intervention is usually recommended when symptoms become evident. We report the case of a 34-year-old woman who presented with a congenital, ruptured sinus of Valsalva aneurysm that originated from the noncoronary cusp. Moderate aortic regurgitation was associated with this lesion. Simple, direct patch closure of the ruptured aneurysm resolved the patient's left-to-right shunt and was associated with decreased aortic regurgitation to a degree that valve replacement was not necessary. Only trace residual aortic regurgitation was evident after 3 months, and the patient remained free of symptoms after 6 months. Our observations support the idea that substantial runoff blood flow in the immediate supra-annular region can be responsible for aortic regurgitation in the absence of a notable structural defect in the aortic valve, and that restoring physiologic flow in this region and equalizing aortic-cusp closure pressure can largely or completely resolve aortic insufficiency. Accordingly, valve replacement may not be necessary in all cases of ruptured sinus of Valsalva aneurysms with associated aortic valve regurgitation.

Lipoprotein-associated phospholipase A2 mass is significantly reduced in dyslipidemic patients treated with lifestyle modification and combination lipid-modifying drug therapy.

Lipoprotein-associated phospholipase A2 (Lp-PLA(2)) mass is a novel inflammatory biomarker. In human blood, Lp-PLA(2) is predominately associated with low-density lipoprotein (LDL). This study examines the ability of lifestyle modification (diet and exercise) and combination lipid therapy to reduce Lp-PLA(2) levels while also determining the relationship between changes in LDL cholesterol and Lp-PLA(2). Thirty dyslipidemic patients who received lifestyle intervention and combination lipid therapy for an average of 6 months were included in these analyses (mean age, 60.9 years); 40% had stable angiographically established coronary artery disease, 40% had the metabolic syndrome, and 70% were men. Drug therapy included omega-3 fish oil, extended-release niacin, colesevelam hydrochloride, and a fixed combination of 10-mg ezetimibe and 40-mg simvastatin. The study revealed a 33% reduction in mean Lp-PLA(2) values (baseline 224.9+/-47.5 vs posttreatment 149.5+/-35.5 ng/mL; P<.001). Significant changes in mean LDL cholesterol from baseline (127.9+/-49.3 vs posttreatment 65.2+/-32.1 mg/dL; P<.001) were also observed. However, regression analysis revealed only a weak positive relationship between changes in LDL cholesterol and Lp-PLA(2) mass (R(2)=0.29; P<.01). Thus, Lp-PLA(2) mass is significantly reduced with lifestyle and combination lipid therapy. Changes in Lp-PLA(2) were only partially explained by the changes observed for LDL cholesterol.

The role of insulin resistance in the pathogenesis of atherosclerotic cardiovascular disease: an updated review.

Insulin resistance is the main pathologic mechanism that links the constellation of clinical, metabolic and anthropometric traits with increased risk for cardiovascular disease and type II diabetes mellitus. These traits include hyperinsulinemia, impaired glucose intolerance, endothelial dysfunction, dyslipidemia, hypertension, and generalized and upper body fat redistribution. This cluster is often referred to as insulin resistance syndrome. The progression of insulin resistance to diabetes mellitus parallels the progression of endothelial dysfunction to atherosclerosis leading to cardiovascular disease and its complications. In fact, insulin resistance assessed by homeostasis model assessment (HOMA) has shown to be independently predictive of cardiovascular disease in several studies and one unit increase in insulin resistance is associated with a 5.4% increase in cardiovascular disease risk. This review article addresses the role of insulin resistance as a main causal factor in the development of metabolic syndrome and endothelial dysfunction, and its relationship with cardiovascular disease. In addition to this, we review the type of lifestyle modification and pharmacotherapy that could possibly ameliorate the effect of insulin resistance and reverse the disturbances in insulin, glucose and lipid metabolism.

Efficacy of combination drug pulse therapy in maintaining lipid levels in patients intolerant of daily statin use.

The objective of this study was to evaluate the efficacy of combination drug pulse therapy in maintaining lipid levels in patients intolerant of a daily dose of statins. Twenty-three patients, previously receiving aggressive statin therapy, were treated twice weekly with rosuvastatin or atorvastatin in different dosages along with ezetimibe as well as daily doses of bile acid sequestrant for a mean period of 4.5 months. The recommended National Cholesterol Education Program Adult Treatment Panel III goals had already been achieved in 78% of patients (n=18) before starting combination pulse therapy. This combination therapy significantly increased high-density lipoprotein cholesterol values by 5.82% (t=2.138, P=.044), while the increases in total cholesterol, low-density lipoprotein cholesterol, triglyceride, and apolipoprotein B levels compared with baseline were not statistically significant. Overall, 3 of 23 patients (13%) discontinued the combination therapy because of muscle-related symptoms over a mean course of 4.5 months of treatment.

The role of lipoprotein-associated phospholipase A2 on cardiovascular disease risk assessment and plaque rupture: a clinical review.

During the last several last decades, reduction in lipids has been the main focus to decrease the risk of coronary heart disease (CHD). Several lines of evidence, however, have indicated that lipids account only for the <50% of variability in cardiovascular risk in the United States. Therefore, for better identification of people at high cardiovascular risk, a more effective and complete approach is required. Our understanding of atherosclerosis has shifted from a focal disease resulting in symptoms caused by severe stenosis to a systemic disease distinguished by plaque inflammation with a potential to rupture and thrombosis, turning a substenotic atherosclerotic lesion into a complete occlusive lesion. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a novel inflammatory biomarker that can provide much needed information about plaque inflammation and plaque stability. Lp-PLA(2) is among the multiple biomarkers that have been associated with increased CHD risk. In this present work, we review the evidence from previous studies addressing the effect of different therapies on decreasing Lp-PLA(2) and the role of direct Lp-PLA(2) inhibitors. This work also briefly reviews the evidence of Lp-PLA(2) clinical utility as a potential marker of vascular inflammation and formation of rupture prone plaques. Additionally, we also discuss the implication of available evidence in context of current cardiovascular inflammatory biomarkers recommendations and the evidence from epidemiologic studies addressing the relationship of Lp-PLA(2) and risk of cardiovascular disease.

Effects of lifestyle counseling and combination lipid-modifying therapy on lipoprotein-associated phospholipase A2 mass concentration.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA(2)) is a novel inflammatory biomarker that is associated with increased cardiovascular disease risk independent of and additive to traditional risk factors. Lp-PLA(2) activity is correlated with the degree of inflammation in the atherosclerotic plaque. In human blood, approximately 80% of Lp-PLA(2) is associated with low-density lipoproteins (LDL). Thus, it is hypothesized that changes in Lp-PLA(2) should imitate the changes in the LDL cholesterol. OBJECTIVE: In this present study, we examined the efficacy of lifestyle intervention and combination lipid-lowering therapy on reducing the Lp-PLA(2) levels and determined the relationship between changes in LDL-C and Lp-PLA(2). METHODS: This retrospective chart review study includes two hundred forty eight patients (58% men and 42% women) who completed the life style intervention in combination with pharmacologic therapy for an average period of 10.5 months. Life style modification included diet and exercise counseling. Combination therapy included omega 3 fish oil (2000mg/d), extended-release niacin (500-1000mg/d), ezetimibe (10mg/d), fenofibrate 160mg/d and colesevelam HCI (1850mg/d), as well as statins. The statins used were either simvastatin (20-40mg/d) or rosuvastatin (5-20mg/d). Sixty five percent (n=161) received low to medium doses of simvastatin, whereas 35% (n=87) received low to medium doses of rosuvastatin. RESULTS: The study revealed a 32.5% reduction in mean Lp-PLA(2) values (baseline 181.1±41.5 vs 122.1±28.1 ng/mL after treatment; P<.001). The change observed in LDL-C was 41%, (baseline 126.2±43 vs 73.9±37.7mg/dL after treatment), which also was significant (P < .001). However, a Pearson correlation test analysis revealed only a weak positive association between changes in Lp-PLA(2) and LDL-C (r(2)=0.052, P < .001). CONCLUSION: Lp-PLA(2) is reduced with the use of life style counseling and combination lipid lowering therapy. Results also revealed that changes in Lp-PLA(2) may be partially explained by the changes in LDL-C.