Elevated Lp(a): Guidance for Identifying and Managing Patients.

Lipoprotein(a) (Lp(a)) is a unique low-density lipoprotein-like lipoprotein that is considered an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis. The Lp(a) molecule also contains apolipoprotein A and apolipoprotein B, which collectively promote atherosclerosis, thrombosis, and inflammation. Lp(a) is highly genetic and minimally responsive to nonpharmacological measures. Lp(a) serum levels ≥125 nmol/L are associated with increased ASCVD risk, but this threshold has not been accepted universally. Elevated Lp(a) is the most common genetic dyslipidemia affecting approximately 20% of the general population. Certain currently available lipid-lowering drugs, including the proprotein convertase subtilisin/kexin type 9 therapies, produce moderate reductions in Lp(a); however, none are indicated for the treatment of elevated Lp(a). There are currently four investigational RNA-based therapeutic agents that reduce Lp(a) by 70% to 100%. Two of these agents are being evaluated for ASCVD risk reduction in adequately powered outcomes trials, with results expected in 2 to 3 years. Until such therapies become available and demonstrate favorable clinical outcomes, strategies for elevated Lp(a) primarily involve early and intensive ASCVD risk factor management.

Lipid lowering therapy: implications of recent clinical trials.

Recent lipid lowering therapy trials have provided important insights on certain agents while also continuing to expand our understanding of atherosclerotic cardiovascular disease (ASCVD) risk. Findings from current trials include the impact of statin therapy on ASCVD among populations with HIV, the benefit of lowering low-density lipoprotein cholesterol with bempedoic acid among patients considered statin intolerant, the safety and efficacy of inclisiran over a 4-year period, another failed attempt for fibrates to reduce ASCVD risk, which omega-3 fatty to utilize for lowering cardiovascular events, 'n-of-1' trials evaluating statin intolerance, and how low-dose rosuvastatin compared with commonly utilized supplements for lowering lipid parameters. Such data help inform so clinicians can optimize lipid lowering therapy and improve ASCVD outcomes.

Atherosclerotic Cardiovascular Disease in Women: Providing Protection With Lipid-altering Agents.

PURPOSE: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in women, yet it remains underdiagnosed, undertreated, and understudied in women compared with men. Although estrogen has provided observational evidence of cardioprotection, randomized controlled trials using hormone replacement therapy have generally produced unfavorable results. METHODS: For this narrative review, a literature search was performed using the key words cardiovascular disease, women, and dyslipidemia in PubMed and Google Scholar with no date limitations. References within each article were also reviewed for additional relevant articles. FINDINGS: Sex-specific risk factors and underrecognized conditions more predominant in women elevate ASCVD risk, creating further clinical challenges, such as the need for accurate risk stratification, compared with in men. Dyslipidemia frequently manifests or worsens during the menopausal transition. Therefore, identification during midlife and implementing lipid-lowering strategies to reduce ASCVD risk is imperative. Women have historically been poorly represented in cardiovascular (CV) outcome trials. However, more recent studies and meta-analyses have indicated that lipid-lowering therapies are equally effective in women and produce similar reductions in CV events and total mortality. Major cholesterol guidelines address many of the challenges that clinicians face when assessing ASCVD risk in women. Key points specific to women include obtaining a detailed history of pregnancy-related conditions, identification of common autoimmune disorders associated with systemic inflammation, and use of 10-year ASCVD risk calculators and imaging modalities (coronary artery calcium) to optimize ASCVD assessment. In terms of treatment, similar to men, women with existing ASCVD or high-risk primary prevention patients should be treated aggressively to achieve ≥50% LDL-C reductions and/or LDL-C goals as low as <55 mg/dL. Appropriate lipid-lowering therapies include high-intensity statins with or without ezetimibe and proprotein convertase subtilisin kexin/type 9 inhibitors. Women with lower ASCVD risk may be considered for low- to moderate-intensity statin therapy (approximately 30%-50% LDL-C reduction). All women, regardless of ASCVD risk category, should implement therapeutic lifestyle changes, which improve many common age-related cardiometabolic conditions. IMPLICATIONS: Although ASCVD and current risk factor trends in women are concerning, numerous evidence-based approaches are available to protect women with ASCVD risk from life-changing CV events.

Identifying patient perceptions and attitudes regarding statin-associated diabetes mellitus: a mixed-methods study.

Aim: The aims of this study were to explore factors that influence initiation and continuation of statin therapy. Patients & methods: Mixed-method design employed with 73 patients completing surveys and 14 patients participating in semi-structured interviews. Results: When lower total cholesterol is achieved, patients' views are favorable while views of statin therapy diminish among those with higher total cholesterol values. All patients are concerned with adverse events including the potential for developing diabetes. However, overall patients believe the benefits of statins outweigh the risk of diabetes. Conclusion: Barriers remain that prevent patients from achieving cholesterol goals and maintaining or initiating statin therapy. Effective strategies to provide accurate information about the risks and benefits of statin therapy, and implementation of shared decision-making to improve medication adherence and persistence are needed.

The statin medications are commonly prescribed agents used to lower cholesterol and prevent cardiovascular events, such as heart attacks. Although these medications are prescribed often, researchers and clinicians have limited understanding regarding the influences involving patients' decision to start or stop a statin. This study was conducted to gain insight on patients' beliefs and attitudes involving statin therapy. We observed that when patients' had lower cholesterol values, favorable views of statins were more common, while views became less favorable when cholesterol levels were higher. All patients were concerned about statin-associated side effects; but overall believed that the benefits of statins outweighed the risks. It is essential that patients' are provided accurate information from their healthcare team regarding the advantages and disadvantages of statin therapy. Such discussions may allow patients to make more informed decisions and help with continuing a statin long term.

Statin-associated muscle symptoms-A review: Individualizing the approach to optimize care.

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, also known as "statins" are considered first-line pharmacologic therapy for reducing low-density lipoprotein cholesterol (LDL-C). They have been demonstrated efficacy in a variety of patients populations to reduce atherosclerotic cardiovascular disease (ASCVD) risk. Like any pharmacologic therapy, however, they are not without possible adverse effects that can lead to discontinuation, thus leading to a loss of benefit. The most common side effect related to statin therapy impacting compliance is musculoskeletal related, commonly referred to as statin-associated muscle systems (SAMS). While the overall incidence is relatively low, the consequences of nonadherence to statin therapy can have a negative impact on patient care. Therefore, it is important for healthcare providers to understand risk factors, how to diagnose, and how to manage this unfortunate adverse effect in order to optimize care.

New and emerging lipid-lowering therapy.

Statins remain the drugs of choice in patients at risk of or with atherosclerotic cardiovascular disease (ASCVD). Statins have limitations that drive the development of investigational agents to manage dyslipidemias and/or reduce ASCVD risk. There are a few small-molecule drugs that have the potential to mitigate ASCVD risk either alone or in combination with statins. Most lipid-modifying drugs in clinical development are biologic agents that target specific enzymes or genetic-based protein synthesis. Limitations of the biologic agents include complex mechanisms of action and manufacturing processes with indications in select patients with genetic dyslipidemia or who have failed traditional therapies. The ultimate clinical utility of the new and investigational agents will become established over the next several years.

Lay abstract The most common medications that reduce fat (cholesterol) in the blood are called 'statins.' Statins reduce the chance of having a heart attack, stroke or cardiac death. Statins do not completely eliminate these risks and some patients cannot tolerate them. New medications are being tested to find out if they reduce the risk of heart problems. Many of the new drugs are called 'biologics.' Biologics work through complex mechanisms to reduce the amount of fat produced or by limiting the toxicity of the fat. Many of the new medications are difficult to manufacture and must be given as injections. They are expensive but possibly effective for patients unable to take statins or patients with rare cholesterol disorders.

Comparing patients' prescribed, self-reported, and actual intake of supplemental eicosapentaenoic acid + docosahexaenoic acid.

BACKGROUND: Dietary fish oil supplements containing the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are frequently used for cardiovascular benefit. However, several factors may limit the intake of prescribed doses. OBJECTIVE: The objective of this study is to compare the prescribed, patient self-reported, and actual intake of supplemental EPA + DHA doses in a lipid-specialty clinic and identify common barriers and influences to therapy. METHODS: Seventy-six patients prescribed supplemental fish oil were randomly selected to participate in a 28-item cross-sectional survey for evaluating patient knowledge and intake of prescribed supplemental EPA + DHA doses. Self-reported data were collected during a follow-up clinic visit, whereas actual intake was determined when patients had access to their fish oil bottle. These data were compared with their chart-documented prescribed EPA + DHA dose. RESULTS: Many patients were well-educated and had attended the lipid-specialty clinic for approximately 2 years but only 28.9% were confident that they could accurately recall their daily EPA + DHA dose. There were statistically significant differences between the prescribed doses and patients' self-reported doses (3600 mg vs 2750 mg, P = .014), as well as between prescribed doses and actual intake (3600 mg vs 1575 mg, P < .001). Patients reported multiple barriers and influences to explain their use of fish oil products. CONCLUSION: Most patients using supplemental fish oil in a lipid-specialty clinic were not taking the prescribed amount of EPA + DHA, with many using markedly lower than prescribed doses. This is likely because of several factors including the complexities of supplemental fish oil doses and labeling, product availability, and discount sales. These findings suggest that supplemental fish oil requires continuous education and dosing guidance.

Variability in Potency Among Commercial Preparations of Berberine.

Berberine is an isoquinoline alkaloid plant extract that is widely available as a dietary supplement in the United States and has demonstrated efficacy in the treatment of type 2 diabetes mellitus and dyslipidemia. Because of its increased use and purported pharmacological properties, potential variations in product quality could pose a barrier to berberine's safety and effectiveness in clinical practice. Thus, this study evaluated the potency of dietary supplements containing berberine available in the U.S. commercial market. Fifteen unique dietary supplements containing berberine were purchased through U.S. dietary supplement vendors. For each product, berberine was extracted from 3 unique capsules and analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry. Percentage content based on the product label claim was determined for each product. The average berberine content across the products was found to be 75% ± 25% of the product label claim, with product potency ranging from 33% to 100%. Nine of the 15 tested products (60%) failed to meet the potency standards of 90% to 110% of labeled content claim, as commonly required of pharmaceutical preparations by the U.S. Pharmacopeial Convention. Evaluation of the relationship between product cost and the measured potency failed to demonstrate an association between quality and cost. Variability in product quality may significantly contribute to inconsistencies in the safety and effectiveness of berberine. In addition, the quality of the berberine product cannot be inferred from its cost.

Statin-associated muscle symptoms-Managing the highly intolerant.

Musculoskeletal symptoms are the most commonly reported adverse effects associated with statin therapy. Yet, certain data indicate that these symptoms often present in populations with underlying musculoskeletal complaints and are not likely statin related. Switching statins or using lower doses resolves muscle complaints in most patients. However, there is a growing population of individuals who experience intolerable musculoskeletal symptoms with multiple statins, regardless of the individual agent or prescribed dose. Recent randomized, placebo-controlled trials enrolling highly intolerant subjects provide significant insight regarding statin-associated muscle symptoms (SAMS). Notable findings include the inconsistency with reproducing muscle complaints, as approximately 40% of subjects report SAMS when taking a statin but not while receiving placebo, but a substantial cohort reports intolerable muscle symptoms with placebo but none when on a statin. These data validate SAMS for those likely experiencing true intolerance, but for others, suggest a psychosomatic component or misattribution of the source of pain and highlights the importance of differentiating from the musculoskeletal symptoms caused by concomitant factors. Managing the highly intolerant requires candid patient counseling, shared decision-making, eliminating contributing factors, careful clinical assessment and the use of a myalgia index score, and isolating potential muscle-related adverse events by gradually reintroducing drug therapy with the utilization of intermittent dosing of lipid-altering agents. We provide a review of recent data and therapeutic guidance involving a focused step-by-step approach for managing SAMS among the highly intolerant. Such strategies usually allow for clinically meaningful reductions in low-density lipoprotein cholesterol and an overall lowering of cardiovascular risk.

Statin-Associated Diabetes Mellitus: Review and Clinical Guide.

A small but significant link between new-onset diabetes mellitus (NOD) and statin therapy was noted with rosuvastatin users in the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin study. Since then multiple analyses have further confirmed this association, with most studies demonstrating a modest increase in NOD with statin therapy, especially among individuals with risk factors for developing diabetes mellitus. More recent observational analyses suggest a stronger correlation between statin use and NOD, however. A definitive mechanism confirming causation between statins and glucose impairment remains elusive, but many have been proposed. Although considered a class effect by the US Food and Drug Administration, most data indicate NOD is dependent upon the dose and potency of the statin, with certain agents appearing to be less diabetogenic. The consensus is that the benefits of statin therapy far outweigh the risk of NOD, especially among patients with high cardiovascular risk. Nonetheless, more studies are needed to better understand this association and long-term clinical implications. In the meantime, we provide clinicians with a practical guide to assist with clinical decision making when prescribing statin therapy. Overall, this article serves to provide the primary care physician with a timely review of the most clinically relevant data regarding statins and NOD, with hopes to ultimately optimize statin prescribing and limit any potential drug-induced glucose impairment.

Hypertriglyceridaemia unresponsive to multiple treatments.

A 52-year-old man with a longstanding history of hypertriglyceridaemia (approximately 7 mmol/L (600 mg/dL)), unresponsive to treatment, presented to a lipid-specialty clinic. Additional triglyceride-lowering therapies were added with no effect. It was then noted that despite the apparent hypertriglyceridaemia, his serum sample was clear. A 'glycerol blank' was then requested from an advanced lipid laboratory, which reported a triglyceride value of 0.7 mmol/L (62 mg/dL). These findings suggest isolated asymptomatic glycerol kinase deficiency (GKD) or 'pseudohypertriglyceridaemia'. The falsely elevated triglyceride values in such individuals are a result of excess serum glycerol and clinical laboratories measuring glycerol to report triglyceride concentrations. After discontinuation or modification of the patient's primary triglyceride-lowering agents, the lipid panels and triglyceride values remained comparable to previous readings. Recognition of asymptomatic GKD is important to prevent unnecessary treatment and overestimated cardiovascular risk.

Statins and almonds to lower lipoproteins (the STALL Study).

BACKGROUND: Dietary supplementation with almonds has demonstrated dose-dependent decreases in low-density lipoprotein cholesterol (LDL-C), likely because of their composition of beneficial nutrients including mono- and polyunsaturated fatty acids, fiber, and protein. OBJECTIVE: The primary objective of this study was to determine the changes in the lipid profile (LDL-C, high-density lipoprotein cholesterol [HDL-C], triglycerides, total cholesterol, non-HDL-C), LDL-C particle size, and lipoprotein (a) when 100 g of almonds daily were added to background statin therapy for 4 weeks. METHODS: Subjects (N = 48) receiving a consistent statin dose were randomized to 100 g of almonds daily and to The National Cholesterol Education Program Adult Treatment Panel's third report Therapeutic Lifestyle Changes Diet counseling (almond group; n = 22) or solely Adult Treatment Panel's third report Therapeutic Lifestyle Changes Diet counseling (non-almond group; n = 26), for 4 weeks. RESULTS: No significant changes in weight and weekly physical activity were noted between the 2 groups from baseline. However, the almond group consumed significantly more calories at 4 weeks compared with controls. The almond group experienced a 4.9% reduction in non-HDL-C compared with a 3.5% increase for the non-almond group (P = .02). Additionally, notable improvements were observed in LDL-C and triglycerides, but did not achieve statistical significance (P = .068 for both parameters). There was also a shift from LDL pattern A to pattern B particles (P = .003) in the almond group. No significant differences in total cholesterol (P = .1), HDL-C (P = .3), or lipoprotein (a) (P = .1) were observed. CONCLUSION: Adding 100 g of almonds daily to chronic statin therapy for 4 weeks significantly reduced non-HDL-C. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00603876.

Krill oil for cardiovascular risk prevention: is it for real?

Omega-3 fatty acids play an important role in cardiovascular health. Although it is suggested that individuals obtain these nutrients through diet, many prefer to rely on supplements. Fish oil supplements are widely used, yet large capsule sizes and tolerability make them less than ideal. Recently, krill oil has emerged as a potential alternative for omega-3 supplementation. This article will discuss what is known about krill oil and its potential use in cardiovascular risk prevention.

Pseudohypertriglyceridemia: two cases of probable glycerol kinase deficiency.

The National Cholesterol Educational Program Adult Treatment Panel's third report define borderline-high, high, and very high triglycerides as serum levels of 150-199 mg/dL, 200-499 mg/dL, and ≥500 mg/dL, respectively. Hypertriglyceridemia (HTG) is generally very responsive to both therapeutic lifestyle changes (TLC), and drug therapy, with niacin, omega-3 fatty acids, fibrates, and statins, each reducing levels by ~10-50%. This paper presents two cases of patients who were aggressively treated for significant HTG with little response to therapy. Although most measured triglyceride (TG) values in these patients were markedly elevated, periodic concentrations were reported as normal. When this occurs, the clinician must immediately think of the diagnosis 'pseudohypertriglyceridemia' or as it is more aptly termed 'glycerolemia' secondary to glycerol kinase deficiency (GKD).

The high-dose rosuvastatin once weekly study (the HD-ROWS).

BACKGROUND: Alternative dosing is often used clinically to address common barriers with statin therapy, such as intolerance and cost. Previous findings have demonstrated significant and clinically similar reductions in low-density lipoprotein (LDL) cholesterol to daily dosing, when comparing similar total weekly doses. OBJECTIVE: To determine whether rosuvastatin 80 mg once weekly produced comparable lipid and high-sensitivity C-reactive protein (hsCRP) changes to atorvastatin 10 mg daily, when measured at key points after last dose. METHODS: This was a randomized, double-blind, parallel group, 8-week pilot study. Eligible subjects, 18 to 65 years of age, had documented dyslipidemia with LDL cholesterol >100 mg/dL and triglycerides <200 mg/dL. Participants were randomized to receive either rosuvastatin 80 mg once weekly (n = 10) or atorvastatin 10 mg daily (n = 10), for 8 weeks. Lipid panels and hsCRP were measured at baseline and 1-4 and 5-8 days after the last dose. RESULTS: Participants in each arm experienced significant and comparable reductions from baseline in total cholesterol, total cholesterol/high-density lipoprotein cholesterol ratio, non-high-density lipoprotein cholesterol, and overall LDL cholesterol (-29%). Changes in high-density lipoprotein cholesterol, triglycerides, and hsCRP were nonsignificant and similar between groups. Each regimen was well tolerated, with no major adverse events reported. CONCLUSION: Rosuvastatin 80 mg once weekly produced comparable lipid changes to atorvastatin 10 mg daily when measured at specific points after the last dose. Our findings support previous data demonstrating a significant reduction in LDL-C with once weekly statin dosing.

Modified-policosanol does not reduce plasma lipoproteins in hyperlipidemic patients when used alone or in combination with statin therapy.

Policosanol is a poorly absorbed nutritional supplement used primarily for cholesterol management. Findings from previous trials evaluating the effects of policosanol are mixed with early data reporting positive lipid effects while more recent studies indicate negligible efficacy. We hypothesized that re-formulating policosanol would result in an improvement in major lipoproteins and possibly provide some explanation for previously conflicting trial data. Our primary objectives were to assess the efficacy and safety of modified-policosanol (MP) on the major lipoproteins among hyperlipidemic subjects receiving background statin therapy or as monotherapy. This 8-week clinical trial consisted of 3 arms. Subjects receiving chronic statin therapy (N = 36) were randomized in a double-blind design to MP 20 mg daily or placebo. In the third arm, subjects not receiving statin therapy (N = 18) were assigned open-label MP 20 mg daily. The utilization of MP when added to background statin therapy or as monotherapy resulted in no significant changes in major lipoproteins (all p > 0.05). The MP therapy was well tolerated with no major adverse events reported. Consistent with recent clinical trial data, MP demonstrated an excellent safety profile but produced no significant effects on major lipoproteins when used as monotherapy or when given with concomitant statin therapy.