Faculty Bibliography

Patients with elevated triglycerides (TG) may be at a higher risk for cardiovascular (CV) disease. Omega-3 fatty acids (OM3FAs), particularly the long-chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), effectively reduce TG and thus may impact CV outcomes; however, clinical data have been inconsistent. This review discusses the efficacy, safety, and key considerations of currently approved prescription OM3FA products in patients with elevated TG with or without concomitant elevations in other atherogenic parameters. Currently, 6 prescription OM3FA formulations are approved in the United States: omega-3-acid ethyl esters (Lovaza, Omtryg, and 2 generic formulations), omega-3-carboxylic acids (Epanova), which contain both EPA and DHA, and icosapent ethyl (Vascepa), which is an EPA-only formulation. All prescription OM3FA products effectively lower TG, with the magnitude of TG reduction affected by baseline TG level. Products that contain DHA can raise levels of low-density lipoprotein cholesterol, which is of particular concern in patients with atherosclerosis; Vascepa, however, does not raise these levels and therefore provides these patients with another option. Long-term outcomes trials for Vascepa (ongoing) and Epanova (planned) will help clarify the potential CV benefits in patients with persistent hypertriglyceridemia despite statin therapy.

BACKGROUND: The American Heart Association recommends targeting 7 cardiovascular (CV) health metrics to reduce morbidity and mortality. Control of these targets in patients undergoing CV intervention is uncertain. METHODS: We prospectively studied patients undergoing elective percutaneous coronary or peripheral intervention from November 2010 to May 2012. We recorded data on patient demographics, clinical characteristics, and social history. Risk factor control was categorized as ideal, intermediate, or poor according to the 7 American Heart Association-defined CV health metrics (smoking status, body mass index, physical activity, diet, cholesterol, blood pressure, and metabolic control). Linear regression model was used to evaluate the association between baseline characteristics and poor CV health. RESULTS: Among 830 consecutive patients enrolled, mean age is 67.3 +/- 10.8 years, 74.2% are male, and 62.1% are white. The adequacy of achievement of ideal CV health is suboptimal in our cohort; the mean number of ideal CV metrics is 2.15 +/- 1.06. Less than 1 in 10 (9.7%) met >/=4 ideal CV health metrics. After multivariate analysis, male sex (P = .04), nonwhite race (P = .01), prior coronary artery disease (P < .01), prior peripheral arterial disease (P < .01), and history of depression (P = .01) were significantly associated with poor CV health. CONCLUSIONS: Among patients referred for elective CV intervention, achievement of ideal CV health is poor. Elective interventions represent an opportunity to identify and target CV health for risk factor control and secondary prevention.

BACKGROUND: -National and international guidelines recommend fasting lipid panel measurement for risk stratification of patients for prevention of cardiovascular (CV) events. Yet, the prognostic value of fasting vs. non-fasting low density lipoprotein cholesterol (LDL-C) is uncertain. METHODS AND RESULTS: -Patients enrolled in the National Health and Nutrition Survey III (NHANES-III), a nationally representative cross-sectional survey performed between 1988 to 1994, were stratified based on fasting status (>/=8 hours or <8 hours) and followed for a mean of 14.0 (+/-0.22) years. Propensity score matching was used to assemble fasting and non-fasting cohorts with similar baseline characteristics. The risk of outcomes as a function of LDL-C and fasting status was assessed using receiver operating characteristic (ROC) curves and bootstrapping methods. The interaction between fasting status and LDL-C was assessed using Cox proportional hazards modeling. Primary outcome was all-cause mortality. Secondary outcome was CV mortality. One-to-one matching based on propensity score yielded 4,299 pairs of fasting and non-fasting individuals. For the primary outcome, fasting LDL-C yielded similar prognostic value as non-fasting LDL-C [C-statistics=0.59 (95% CI 0.57-0.61) vs. 0.58 (95% CI 0.56-0.60; P=0.73], and LDL-C by fasting status interaction term in the Cox proportional hazard model was not significant (Pinteraction=0.11). Similar results were seen for the secondary outcome [fasting vs. non-fasting C-statistics=0.62 (95% CI 0.60-0.66) vs. 0.62 (95% CI 0.60-0.66); P=0.96; and Pinteraction=0.34]. CONCLUSIONS: -Non-fasting LDL-C has similar prognostic value as that of fasting LDL-C. National and international agencies should consider re-evaluating the recommendation that patients fast before obtaining a lipid panel.

Statins are the first line pharmacotherapy for cholesterol reduction. Use of these drugs in large, randomized clinical trials have consistently shown significant reductions in major vascular events including death, myocardial infarction, stroke, and coronary revascularization. The updated guidelines for the treatment of high blood cholesterol from the ACC/AHA, will lead to a rise in the number of patients taking statins. Hence, statin intolerance may subsequently increase, emphasizing the need to understand and treat this important problem.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 11 April 2014; doi:10.1038/clpt.2014.84.

OBJECTIVEThe aim of this study was to investigate the relationship between diabetes and different phenotypes of peripheral vascular disease (lower extremity peripheral artery disease [PAD], carotid artery stenosis [CAS], and abdominal aortic aneurysm [AAA]).RESEARCH DESIGN AND METHODSPrevalence of vascular disease was evaluated in 3,696,778 participants of the Life Line Screening survey between 2003 and 2008. PAD was defined as ankle-brachial pressure index <0.90 or prior revascularization, CAS as >/=50% stenosis or prior revascularization, and AAA as infrarenal aortic diameter >/=3 cm or prior repair. Odds ratios (ORs) and 95% CIs were assessed using logistic regression modeling.RESULTSDiabetes mellitus was present in 10.8% of participants (n = 399,884). Prevalence of PAD, CAS, and AAA were significantly higher (P < 0.0001) in participants with compared with those without diabetes. After multivariate adjustment for baseline demographics and clinical risk factors, a significant interaction existed between diabetes and vascular disease phenotype (P < 0.0001). Diabetes was associated with increased odds of PAD (OR 1.42 [95% CI 1.41-1.4]; P < 0.0001) and CAS (1.45 [1.43-1.47]; P < 0.0001) but decreased odds of AAA (0.86 [0.84-0.88]; P < 0.0001). The strength of association increased with increasing severity of disease in each vascular phenotype, and this association persisted in the population with asymptomatic vascular disease.CONCLUSIONSIn a large population-based study, the association between diabetes and vascular disease differed according to vascular phenotype. Future studies exploring the mechanism for these vascular-specific differences are needed.

OPINION STATEMENT: With the advent of noninvasive 24-hour ambulatory blood pressure monitoring (ABPM), clinicians have access to a wealth of individualized data for the hypertensive patient. This has led to a greater understanding of the pathophysiology of hypertension and its complications. This tool has provided more precise diagnostic criteria for hypertension and helped discover those with white coat and masked hypertension. Patterns noted on ABPM and correlated with outcomes have allowed for more accurate identification of patients at high risk of cardiovascular (CV) events, and have offered an additional prognostic tool. In addition, ABPM allows for the assessment of the efficacy and adequacy of blood pressure treatment. In the current paper, we will describe the essential components of ABPM, review the evidence detailing the prognostic information that can be derived from its use, highlight clinical scenarios wherein ABPM can offer invaluable diagnostic information, and describe applications of ABPM that evaluate the efficacy of treatment of the hypertensive patient.

Despite a better understanding of cardiovascular risk factors and attempts at optimal management, diabetes-related macrovascular events remain a significant cause of morbidity and mortality in the United States and worldwide. The trials to date have validated strict glycemic control as a method to achieve sustained reductions in the rate of nephropathy, neuropathy, and retinopathy due to diabetes. For these microvascular complications, the closer hemoglobin A1c is to normal levels, the better the outcome. Although reducing hemoglobin A1c levels to 7% has been shown to reduce macrovascular events, demonstrating an additional reduction in macrovascular events with tighter glycemic control has been more difficult to achieve. A careful review of recent trials, however, has demonstrated that treatment early in the disease course and the ability to safely maintain lower hemoglobin A1c levels might be critical factors in further reducing macrovascular events. In conclusion, with the introduction of novel antidiabetic agents, future trials using these drugs might be able to definitively establish the safety and efficacy of reducing cardiovascular events with stringent glycemic control; however, the current evidence is inconsistent.

Low-density lipoprotein cholesterol (LDL-C) is currently the primary target in the management of dyslipidemia, and statins are first-line pharmacologic interventions. Adjunct therapy such as niacins, fibrates, bile acid sequestrants, or cholesterol absorption inhibitors may be considered to help reduce cardiovascular risk. This review discusses the need for alternative adjunct treatment options and the potential place for omega-3 fatty acids as such. The cardiovascular benefits of fish consumption are attributed to the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and a variety of omega-3 fatty acid products are available with varied amounts of EPA and DHA. The product types include prescription drugs, food supplements, and medical foods sourced from fish, krill, algal and plant oils or purified from these oils. Two prescription omega-3 fatty acids are currently available, omega-3 fatty acid ethyl esters (contains both EPA and DHA ethyl esters), and icosapent ethyl (IPE; contains high-purity EPA ethyl ester). A pharmaceutical containing free fatty acid forms of omega-3 is currently in development. Omega-3 fatty acid formulations containing EPA and DHA have been shown to increase LDL-C levels while IPE has been shown to lower triglyceride levels without raising LDL-C levels, alone or in combination with statin therapy. In addition, recent studies have not been able to demonstrate reduced cardiovascular risk following treatment with fibrates, niacins, cholesterol absorption inhibitors, or omega-3 fatty acid formulations containing both EPA and DHA in statin-treated patients; thus, there remains a need for further cardiovascular outcomes studies for adjunct therapy.

OPINION STATEMENT: Triglycerides are routinely obtained with standard lipid testing, but their role in cardiovascular risk is controversial. An excess of triglycerides is commonly encountered in patients with the metabolic syndrome or diabetes, and represents an excess burden of small, dense low-density lipoproteins (LDLs), which confers additive risk for cardiovascular disease. Current guidelines prioritize LDL targets first, but treatment of triglycerides once LDL targets are achieved bears consideration. Beyond lifestyle modification, potential pharmacologic therapies include statins, fibrates, niacin, omega-3 fatty acids and antidiabetic drugs. There are few trials to date comparing these agents directly in the management of hypertriglyceridemia, but available data seems to demonstrate that the greatest benefit of triglyceride lowering is experienced in a subgroup of patients with an atherogenic lipid profile (elevated triglycerides, low high-density lipoprotein (HDL), elevated small, dense LDL particles). Here, we discuss the current understanding of how triglyceride elevations impart cardiovascular risk, current therapies and the data supporting their use, and ongoing studies to elucidate the degree to which treatment of triglycerides modifies risk of future cardiovascular events.