Review of Cardiometabolic Effects of Prescription Omega-3 Fatty Acids.

PURPOSE OF REVIEW: Populations with significant dietary fish intake tend to have lower cardiovascular (CV) risk and demonstrable physiologic differences including lower lipid/lipoprotein levels and other direct and indirect effects on the arterial wall and inhibiting factors that promote atherosclerosis. Treatment with high doses of pharmacologic-grade omega-3 fatty acid (n-3FA) supplements achieves significant reductions in triglycerides (TG), non-high-density lipoprotein- (non-HDL-) and TG-rich lipoprotein- (TRL-) cholesterol levels. n-3FA supplements have significant effects on markers of atherosclerosis risk including endothelial function, low-density lipoprotein (LDL) oxidation, cellular and humoral markers of inflammation, hemodynamic factors, and plaque stabilization. This review summarizes the lipid and cardiometabolic effects of prescription-grade n-3FAs and will discuss clinical trials, national/organizational guidelines, and expert opinion on the impact of supplemental n-3FAs on CV health and disease. RECENT FINDINGS: Clinical trial evidence supports use of n-3FAs in individuals with established atherosclerotic cardiovascular disease (ASCVD), but the data either does not support or is lacking for other types of cardiometabolic risk including prevention of stroke, treatment in patients with heart failure, diabetes mellitus and prediabetes, and for primary prevention in the general population. Despite inconsistent findings to support widespread benefit, there is persistent population-wide enthusiasm for n-3FA as a dietary supplement for its cardiometabolic benefits. Fortunately, there are ongoing clinical trials to assess whether the lipid/lipoprotein benefits may be extended to other at-risk populations and whether lower-dose therapy may provide background benefit for primary prevention of ASCVD.

Attitudes and barriers to lipoprotein(a) testing: A survey of providers at the University of Pennsylvania Health System.

Guidelines recommend checking lipoprotein(a) [Lp(a)] levels in patients at high-risk for cardiovascular disease, with more recent recommendations advocating for universal screening in all adults. A brief electronic survey was distributed to select groups of University of Pennsylvania Health System (UPHS) providers, including Internal Medicine and Cardiology physicians and advance practice providers, to understand the current attitudes and barriers to testing for Lp(a). Of the 126 survey respondents, only 31 % answered that they test for Lp(a) regularly in their practice. Presence of ASCVD and a family history of ASCVD were the most common reasons for testing. Most survey respondents (69 %) replied that they do not currently check Lp(a) levels in patients. The most common reasons provided included lack of familiarity with Lp(a), insurance/ billing concerns, lack of clinical trial outcomes data, and lack of available pharmaceutical interventions. Results from ongoing clinical trials of novel Lp(a)-lowering therapies, if successful, may address provider hesitation toward Lp(a)-testing, but there remains a large gap to fill in awareness of Lp(a).

What's next for lipoprotein(a)? A national lipid association report from an expert panel discussion.

This is an exciting time in the lipoprotein(a) (Lp(a)) field. Attention to this important lipoprotein and potent cardiovascular risk marker is transitioning from the purview of the specialist to that of the general practitioner. Its clinical adoption as an important test is increasing in momentum. There is evidence that Lp(a) contributes to the pathology of atherothrombotic disease, aortic valve stenosis, and childhood ischemic strokes. Three large, Phase 3, randomized, cardiovascular outcomes trials in which Lp(a) is specifically and substantially lowered by mRNA-directed therapies in secondary prevention settings are in progress and will start to report results as early as 2025. Regardless of outcomes, there remain many unanswered questions about Lp(a), ranging from fundamental unknowns about Lp(a) biology, to the complexity of its measurement, optimal screening strategies, and clinical management in individuals with high Lp(a) levels both with and without overt cardiovascular disease. Accordingly, The National Lipid Association (NLA) convened an Expert Discussion involving clinicians and fundamental researchers to identify knowledge gaps in our understanding of Lp(a) biology and pathogenicity and to discuss approaches in the management of elevated Lp(a) in different clinical settings. (183 words).

Using Guidelines of Care to Lower Cardiovascular Risk in Patients with Psoriasis.

National guidelines define psoriasis as a risk enhancer for cardiovascular disease and recommend increased monitoring and more intense management of cardiovascular risk factors in these patients, who face an increased burden of cardiovascular disease morbidity and mortality. Screening for modifiable cardiovascular risk factors, including blood pressure, weight, cholesterol, glucose, and smoking, can be efficiently incorporated into routine dermatology clinical practice. Partnerships with primary care providers and preventive cardiologists are essential to improving management of cardiovascular risk in patients with psoriasis.

Advances in targeting LDL cholesterol: PCSK9 inhibitors and beyond.

There is a direct relationship between the duration and level of exposure to low density lipoprotein cholesterol (LDL-C) levels over one's lifespan and cardiovascular events. Early treatment to lower elevated LDL-C is crucial for better outcomes with multiple therapies currently available to reduce atherogenic lipoproteins. Statins remain the foundation of LDL-C lowering therapy as one of the most cost-effective drugs to reduce atherosclerotic events (ASCVD) and mortality. Nonetheless, LDL-driven goal attainment remains suboptimal globally, highlighting a considerable need for non-statin therapies to address residual risk related to statin intolerance, non-adherence, and inherited lipoprotein disorders. LDL-C lowering interventions beyond statins include ezetimibe, PCSK9 monoclonal antibodies, inclisiran and bempedoic acid with specific guideline recommendations as to when to consider each. For patients with homozygous familial hypercholesterolemia requiring more advanced therapy, lomitapide and evinacumab are available, providing mechanisms that are not LDL receptor dependent. Lipoprotein apheresis remains an effective option for clinical familial hypercholesterolemia as well as elevated lipoprotein (a). There are investigational therapies being explored to add to our current armamentarium including CETP inhibitors, a third-generation PCSK9 inhibitor (small recombinant fusion protein oral PCSK9 inhibitor) and gene editing which aims to directly restore or disrupt genes of interest at the DNA level. This article is a brief review of the pharmacotherapy options beyond statins for lowering LDL-C and their impact on ASCVD risk reduction. Our primary aim is to guide physicians on the role these therapies play in achieving appropriate LDL-C goals, with an algorithm of when to consider each based on efficacy, safety and outcomes.

Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: An expert clinical consensus from the national lipid association.

This National Lipid Association (NLA) Expert Clinical Consensus provides an overview of the physiologic and clinical considerations regarding the role of apolipoprotein B (apoB) measurement to guide clinical care based on the available scientific evidence and expert opinion. ApoB represents the total concentration of atherogenic lipoprotein particles in the circulation and more accurately reflects the atherogenic burden of lipoproteins when compared to low-density lipoprotein cholesterol (LDL-C). ApoB is a validated clinical measurement that augments the information found in a standard lipoprotein lipid panel; therefore, there is clinical value in using apoB in conjunction with a standard lipoprotein lipid profile when assessing risk and managing lipid-lowering therapy (LLT). ApoB has been shown to be superior to LDL-C in risk assessment both before and during treatment with LLT. In individuals, there can be discordance between levels of LDL-C and apoB, as well as LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C), despite high levels of population-wide correlation. When there is discordance between LDL-C and apoB, or LDL-C and non-HDL-C, atherosclerotic cardiovascular disease risk generally aligns better with apoB or non-HDL-C. Additionally, apoB can be used in tandem with standard lipoprotein lipid measurements to diagnose distinct lipoprotein phenotypes. ApoB testing can inform clinical prognosis and care, as well as enable family cascade screening, when an inherited lipoprotein syndrome is identified. The NLA and other organizations will continue to educate clinicians about the role of apoB measurement in improving clinical risk assessment and dyslipidemia management. An urgent need exists to improve access and reimbursement for apoB testing.

New approaches to triglyceride reduction: Is there any hope left?

Triglycerides play a crucial role in the efficient storage of energy in the body. Mild and moderate hypertriglyceridemia (HTG) is a heterogeneous disorder with significant association with atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, ischemic stroke, and peripheral artery disease and represents an important component of the residual ASCVD risk in statin treated patients despite optimal low-density lipoprotein cholesterol reduction. Individuals with severe HTG (>1,000 mg/dL) rarely develop atherosclerosis but have an incremental incidence of acute pancreatitis with significant morbidity and mortality. HTG can occur from a combination of genetic (both mono and polygenic) and environmental factors including poor diet, low physical activity, obesity, medications, and diseases like insulin resistance and other endocrine pathologies. HTG represents a potential target for ASCVD risk and pancreatitis risk reduction, however data on ASCVD reduction by treating HTG is still lacking and HTG-associated acute pancreatitis occurs too rarely to effectively demonstrate treatment benefit. In this review, we address the key aspects of HTG pathophysiology and examine the mechanisms and background of current and emerging therapies in the management of HTG.

A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice.

Since the 2019 National Lipid Association (NLA) Scientific Statement on Use of Lipoprotein(a) in Clinical Practice was issued, accumulating epidemiological data have clarified the relationship between lipoprotein(a) [Lp(a)] level and cardiovascular disease risk and risk reduction. Therefore, the NLA developed this focused update to guide clinicians in applying this emerging evidence in clinical practice. We now have sufficient evidence to support the recommendation to measure Lp(a) levels at least once in every adult for risk stratification. Individuals with Lp(a) levels <75 nmol/L (30 mg/dL) are considered low risk, individuals with Lp(a) levels ≥125 nmol/L (50 mg/dL) are considered high risk, and individuals with Lp(a) levels between 75 and 125 nmol/L (30-50 mg/dL) are at intermediate risk. Cascade screening of first-degree relatives of patients with elevated Lp(a) can identify additional individuals at risk who require intervention. Patients with elevated Lp(a) should receive early, more-intensive risk factor management, including lifestyle modification and lipid-lowering drug therapy in high-risk individuals, primarily to reduce low-density lipoprotein cholesterol (LDL-C) levels. The U.S. Food and Drug Administration approved an indication for lipoprotein apheresis (which reduces both Lp(a) and LDL-C) in high-risk patients with familial hypercholesterolemia and documented coronary or peripheral artery disease whose Lp(a) level remains ≥60 mg/dL [∼150 nmol/L)] and LDL-C ≥ 100 mg/dL on maximally tolerated lipid-lowering therapy. Although Lp(a) is an established independent causal risk factor for cardiovascular disease, and despite the high prevalence of Lp(a) elevation (∼1 of 5 individuals), measurement rates are low, warranting improved screening strategies for cardiovascular disease prevention.

Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force.

Historically, low-carbohydrate (CHO) and very-low-CHO diets have been used for weight loss. Recently, these diets have been promoted for type 2 diabetes (T2D) management. This scientific statement provides a comprehensive review of the current evidence base available from recent systematic reviews and meta-analyses on the effects of low-CHO and very-low-CHO diets on body weight, lipoprotein lipids, glycemic control, and other cardiometabolic risk factors. In addition, evidence on emerging risk factors and potential safety concerns of low-CHO and very-low-CHO diets, especially for high-risk individuals, such as those with genetic lipid disorders, was reviewed. Based on the evidence reviewed, low-CHO and very-low-CHO diets are not superior to other dietary approaches for weight loss. These diets may have advantages related to appetite control, triglyceride reduction, and reduction in the use of medication in T2D management. The evidence reviewed showed mixed effects on low-density lipoprotein cholesterol levels with some studies showing an increase. There was no clear evidence for advantages regarding effects on other cardiometabolic risk markers. Minimal data are available regarding long-term (>2 years) efficacy and safety. Clinicians are encouraged to consider the evidence discussed in this scientific statement when counseling patients on the use of low-CHO and very-low-CHO diets.

Carotid artery stenting in elderly patients: importance of case selection.

OBJECTIVES: This study was conducted to determine if carotid stenting (CS) could be safely performed in the elderly. BACKGROUND: Age has been shown to be a predictor of neurological complications during CS. We postulated that CS could be safely performed in elderly patients if certain anatomical and clinical markers such as excessive vascular tortuosity, heavy concentric calcification of the lesion, and decreased cerebral reserve were avoided. METHODS: From July 2003 to October 2007, 142 patients aged > or =50% or asymptomatic stenosis > or =70%. All patients underwent carotid and cerebral angiography to determine anatomic suitability and stent risk. Demographic and outcome data were entered into a database; other data were obtained retrospectively. Independent neurology evaluation was performed before and at 24 hr after the procedure. RESULTS: The mean age was 83.2 years, 62% were male, 25.5% were symptomatic, 8.5% had postcarotid endarterectomy restenosis, and 6.0% had contralateral internal carotid artery occlusion. There were no intracranial hemorrhages or periprocedural myocardial infarctions. One patient had amaurosis fugax. There were two minor and three major strokes in-hospital (3.3%). All patients had 30-day follow-up. One of the major strokes expired. Thus the overall 30-day stroke or death rate was 3.3% and major stroke or death rate was 2.0%. The 30-day stroke or death rate was 5.1% for symptomatic patients and 2.6% for asymptomatic patients. CONCLUSION: CS can be performed safely in anatomically suitable elderly patients with low adverse event rates. CS should remain a revascularization option in appropriately selected elderly patients.