Prevalence of Aortic Valve Calcium and the Long-Term Risk of Incident Severe Aortic Stenosis.

BACKGROUND: Aortic valve calcification (AVC) is a principal mechanism underlying aortic stenosis (AS). OBJECTIVES: This study sought to determine the prevalence of AVC and its association with the long-term risk for severe AS. METHODS: Noncontrast cardiac computed tomography was performed among 6,814 participants free of known cardiovascular disease at MESA (Multi-Ethnic Study of Atherosclerosis) visit 1. AVC was quantified using the Agatston method, and normative age-, sex-, and race/ethnicity-specific AVC percentiles were derived. The adjudication of severe AS was performed via chart review of all hospital visits and supplemented with visit 6 echocardiographic data. The association between AVC and long-term incident severe AS was evaluated using multivariable Cox HRs. RESULTS: AVC was present in 913 participants (13.4%). The probability of AVC >0 and AVC scores increased with age and were generally highest among men and White participants. In general, the probability of AVC >0 among women was equivalent to men of the same race/ethnicity who were approximately 10 years younger. Incident adjudicated severe AS occurred in 84 participants over a median follow-up of 16.7 years. Higher AVC scores were exponentially associated with the absolute risk and relative risk of severe AS with adjusted HRs of 12.9 (95% CI: 5.6-29.7), 76.4 (95% CI: 34.3-170.2), and 380.9 (95% CI: 169.7-855.0) for AVC groups 1 to 99, 100 to 299, and ≥300 compared with AVC = 0. CONCLUSIONS: The probability of AVC >0 varied significantly by age, sex, and race/ethnicity. The risk of severe AS was exponentially higher with higher AVC scores, whereas AVC = 0 was associated with an extremely low long-term risk of severe AS. The measurement of AVC provides clinically relevant information to assess an individual's long-term risk for severe AS.

Comparing eligibility for statin therapy for primary prevention under 2022 USPSTF recommendations and the 2018 AHA/ACC/ multi-society guideline recommendations: From National Health and Nutrition Examination Survey.

INTRODUCTION: The United States Preventive Services Taskforce (USPSTF) recently released recommendations for statin therapy eligibility for the primary prevention of cardiovascular disease (CVD). We report the proportion and the absolute number of US adults who would be eligible for statin therapy under these recommendations and compare them with the previously published 2018 American Heart Association (AHA)/ American College of Cardiology (ACC)/ Multisociety (MS) Cholesterol guidelines. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 of adults aged 40-75 years without prevalent self-reported atherosclerotic CVD (ASCVD) and low-density lipoprotein-cholesterol <190 mg/dL. The 2022 USPSTF recommends statin therapy for primary prevention in those with a 10-year ASCVD risk of ≥10% and ≥ 1 CVD risk factor (diabetes mellitus, dyslipidemia, hypertension, or smoking). The 2018 AHA/ ACC/ MS Cholesterol guideline recommends considering statin therapy for primary prevention for those with diabetes mellitus, or 10-year ASCVD risk ≥20% or 10-year ASCVD risk 7.5 to <20% after accounting for risk-enhancers and shared decision making. Survey recommended weights were used to project these proportions to national estimates. RESULTS: Among 1799 participants eligible for this study, the weighted mean age was 56.0 ± 0.5 years, with 53.0% women (95% confidence interval [CI] 49.7, 56.3), and 10.6% self-reported NH Black individuals (95% CI 7.7, 14.3). The weighted mean 10-year ASCVD risk was 9.6 ± 0.3%. The 2022 USPSTF recommendations and the 2018 AHA/ ACC/ MS Cholesterol guidelines indicated eligibility for statin therapy in 31.8% (95% CI 28.6, 35.1) and 46.8% (95% CI 43.0, 50.5) adults, respectively. These represent 33.7 million (95% CI 30.4, 37.2) and 49.7 million (95% CI 45.7, 53.7) adults, respectively. For those with diabetes mellitus, 2022 USPSTF recommended statin therapy in 63.0% (95% CI 52.1, 72.7) adults as compared with all adults with diabetes aged 40-75 years under the 2018 AHA/ ACC/ MS Cholesterol guidelines. CONCLUSION: In this analysis of the nationally representative US population from 2017 to 2020, approximately 15% (~16.0 million) fewer adults were eligible for statin therapy for primary prevention under the 2022 USPSTF recommendations as compared to the 2018 AHA/ ACC/ MS Cholesterol guideline.

Omega-3 fatty acids, subclinical atherosclerosis, and cardiovascular events: Implications for primary prevention.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: Mean ± SD age was 62.1 ± 10.2 years and 52.9% were females. The median follow-up time was 15.6 years. Higher loge(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.94) and loge(DHA) (aHR = 0.79; 95% CI, 0.66-0.96) were independently associated with fewer CVD events. The difference in absolute CVD event rates between lowest vs. highest EPA tertile increased at higher CAC levels. The adjusted HR for highest vs. lowest EPA tertile within CAC = 0 was 1.02 (95% CI, 0.72-1.46), CAC = 1-99 was 0.71 (95% CI, 0.51-0.99), and CAC≥100 was 0.67 (95% CI, 0.52-0.84). A similar association was seen in tertiles of DHA by CAC category. CONCLUSIONS: In 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.

Controversies in the Use of Omega-3 Fatty Acids to Prevent Atherosclerosis.

PURPOSE OF REVIEW: We discuss current controversies in the clinical use of omega-3 fatty acids (FA), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and examine discrepancies between recent trials. Furthermore, we discuss potential side effects reported in these studies and the role of mixed omega-3 FA dietary supplements and concerns about their use. RECENT FINDINGS: REDUCE-IT showed that addition of icosapent ethyl, a highly purified form of EPA, can reduce risk of cardiovascular events among statin-treated individuals with high triglycerides. Additional supportive evidence for EPA has come from other trials and meta-analyses of omega-3 FA therapy. In contrast, trials of mixed EPA/DHA products have consistently failed to improve cardiovascular outcomes. Discrepancies in results reported in RCTs could be explained by differences in omega-3 FA products, dosing, study populations, and study designs including the placebo control formulation. Evidence obtained from highly purified forms should not be extrapolated to other mixed formulations, including "over-the-counter" omega-3 supplements. Targeting TG-rich lipoproteins represents a new frontier for mitigating ASCVD risk. Clinical and basic research evidence suggests that the use of omega-3 FA, specifically EPA, appears to slow atherosclerosis by reducing triglyceride-rich lipoproteins and/or inflammation, therefore addressing residual risk of clinical ASCVD.

Update on the omega-3 fatty acid trial landscape: A narrative review with implications for primary prevention.

Residual risk mediated by hypertriglyceridemia among statin-treated individuals is an important clinical and public health challenge. Niacin, fibrates and omega-3 FA are three classes of non-statin agents with demonstrated TG-lowering effects. Randomized controlled trials of niacin and fibrates have been consistently negative, but the trial landscape for two key sources of omega-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is more complex. Clinical trials evaluating omega-3 FA can be differentiated into those that studied mixed formulations (EPA + DHA) and those that studied EPA alone. Those assessing the impact of mixed formulations have not consistently demonstrated CVD risk reduction, whereas trials of EPA alone have been successful. Two recent trials of mixed formulations - STRENGTH (Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia) and OMEMI (Omega-3 fatty acids in Elderly patients with Myocardial Infarction) - studied contemporarily treated patients with mixed EPA + DHA formulations at higher doses than before and showed no benefit, thus adding valuable information to our overall understanding of this evolving therapeutic class. In this review, we contextualize the findings of STRENGTH and OMEMI within the existing omega-3 FA clinical trial landscape and look ahead to how future trials can inform existing knowledge gaps, particularly with regards to the applicability of these agents within the primary prevention realm.

Association Between Omega-3 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA.

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.

Spotlight on Icosapent Ethyl for Cardiovascular Risk Reduction: Evidence to Date.

Icosapent ethyl is a highly purified formulation of eicosapentaenoic acid, a type of omega-3 fatty acid contained in fish oil. While omega-3 fatty acids have long been thought to have cardioprotective benefits, the Reduction of Cardiovascular Events with EPA-Intervention Trial (REDUCE-IT) has helped to establish icosapent ethyl as an evidence-based therapy for risk reduction of atherosclerotic cardiovascular disease (ASCVD). REDUCE-IT, however, was by no means an overnight success story. Close examination of the evidence shows that the trial was a culmination of many lessons learned from previous studies. The purpose of this manuscript is to review contemporary evidence of icosapent ethyl in ASCVD risk reduction and the clinical implication of this promising therapy.

Synergistic Opportunities in the Interplay Between Cancer Screening and Cardiovascular Disease Risk Assessment: Together We Are Stronger.

Cardiovascular disease (CVD) and cancer continue to be the 2 leading causes of death in developed countries despite significant improvements in the prevention, screening, and treatment of both diseases. They remain significant public health problems, growing in importance globally. Despite this threat, the fields of cardiology and oncology have been relatively disconnected. With many shared modifiable risk factors, cancer and CVD often coexist in the same individuals; those diagnosed with lung cancer, breast cancer, and colon cancer are at higher risk of CVD, and those with CVD are at higher risk of developing many types of common cancers. Screening paradigms have been established in parallel, but there are opportunities for combined risk assessments for cancer and CVD risk. Joining forces for combined cardiovascular and hemato-oncological preventive and research efforts will likely have synergistic, worldwide public health benefits.

Association of Multivitamin and Mineral Supplementation and Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple studies have attempted to identify the association between multivitamin/mineral (MVM) supplementation and cardiovascular disease (CVD) outcomes, but the benefits remain controversial. We performed a systematic review and meta-analysis of the associations between MVM supplementation and various CVD outcomes, including coronary heart disease (CHD) and stroke. METHODS AND RESULTS: We conducted a comprehensive search of Medline, Embase, and the Cochrane Library for studies published between January 1970 and August 2016. We included clinical trials and prospective cohort studies in the general population evaluating associations between MVM supplementation and CVD outcomes. Data extraction and quality assessment were independently conducted by 2 authors, and a third author resolved discrepancies. Eighteen studies with 2 019 862 participants and 18 363 326 person-years of follow-up were included in the analysis. Five studies specified the dose/type of MVM supplement and the rest did not. Overall, there was no association between MVM supplementation and CVD mortality (relative risk [RR], 1.00; 95% confidence interval [CI], 0.97-1.04), CHD mortality (RR, 1.02; 95% CI, 0.92-1.13), stroke mortality (RR, 0.95; 95% CI, 0.82-1.09), or stroke incidence (RR, 0.98; 95% CI, 0.91-1.05). There was no association between MVM supplements and CVD or CHD mortality in prespecified subgroups categorized by mean follow-up period, mean age, period of MVM use, sex, type of population, exclusion of patients with history of CHD, and adjustment for diet, adjustment for smoking, adjustment for physical activity, and study site. In contrast, MVM use did seem to be associated with a lower risk of CHD incidence (RR, 0.88; 95% CI, 0.79-0.97). However, this association did not remain significant in the pooled subgroup analysis of randomized controlled trials (RR, 0.97; 95% CI, 0.80-1.19). CONCLUSIONS: Our meta-analysis of clinical trials and prospective cohort studies demonstrates that MVM supplementation does not improve cardiovascular outcomes in the general population.

Associations of Coffee, Tea, and Caffeine Intake with Coronary Artery Calcification and Cardiovascular Events.

BACKGROUND: Coffee and tea are 2 of the most commonly consumed beverages in the world. The association of coffee and tea intake with coronary artery calcium and major adverse cardiovascular events remains uncertain. METHODS: We examined 6508 ethnically diverse participants with available coffee and tea data from the Multi-Ethnic Study of Atherosclerosis. Intake for each was classified as never, occasional (<1 cup per day), and regular (≥1 cup per day). A coronary artery calcium progression ratio was derived from mixed effect regression models using loge(calcium score+1) as the outcome, with coefficients exponentiated to reflect coronary artery calcium progression ratio versus the reference. Cox proportional hazards analyses were used to evaluate the association between beverage intake and incident cardiovascular events. RESULTS: Over a median follow-up of 5.3 years for coronary artery calcium and 11.1 years for cardiovascular events, participants who regularly drank tea (≥1 cup per day) had a slower progression of coronary artery calcium compared with never drinkers after multivariable adjustment. This correlated with a statistically significant lower incidence of cardiovascular events for ≥1 cup per day tea drinkers (adjusted hazard ratio 0.71; 95% confidence interval 0.53-0.95). Compared with never coffee drinkers, regular coffee intake (≥1 cup per day) was not statistically associated with coronary artery calcium progression or cardiovascular events (adjusted hazard ratio 0.97; 95% confidence interval 0.78-1.20). Caffeine intake was marginally inversely associated with coronary artery calcium progression. CONCLUSIONS: Moderate tea drinkers had slower progression of coronary artery calcium and reduced risk for cardiovascular events. Future research is needed to understand the potentially protective nature of moderate tea intake.

A national interactive web-based physical activity intervention in women, evaluation of the american heart association choose to move program 2006-2007.

Increased physical activity (PA) is associated with improvement of cardiac risk factors and prevention of cardiovascular disease, yet many women remain sedentary. With rising Internet use, Web-based interventions provide an alternative to improve PA, but their effectiveness for change in PA and quality of life (QOL) in a real-world setting is unknown. Participants were United States women ≥18 years old who received 12 weekly PA modules and completed surveys on PA, QOL, and readiness for PA at registration (registration cohort, n = 3,796) or registration and 12 weeks (evaluation cohort, n = 892). QOL was assessed with a modified Short Form-36 with subscores for energy and well-being. Participants showed significant (p <0.001) favorable changes in PA (baseline, median 240 kcal/week, interquartile range 62 to 667; 12 weeks, 343 kcal/week, 131 to 828), stage of readiness for PA, and body mass index (baseline, 29.3 kg/m(2), 24.9 to 34.7; 12 weeks, 28.9 kg/m(2), 24.6 to 34.2). Significant improvements (p <0.0001) were also found in composite scores for energy and well-being. Compliance with PA guideline recommendations increased from 15.8% to 21.4%. Program weeks completed (p = 0.03), energy (p = 0.04), and well-being (p = 0.002) were significantly associated with achieving guideline compliance. In women reporting no PA at baseline (n = 88), program participation resulted in 54.6% achieving some PA and another 9.1% achieving total compliance with recommendations. In conclusion, in this national cohort of women, a 12-week Web-based intervention improved PA and QOL measurements, resulting in higher short-term PA guideline compliance and better QOL. Increasing use of this simple Web-based tool could improve PA and promote disease prevention.

Thoracic aortic calcification and coronary heart disease events: the multi-ethnic study of atherosclerosis (MESA).

BACKGROUND: The presence and extent of coronary artery calcium (CAC) is an independent predictor of coronary heart disease (CHD) morbidity and mortality. Few studies have evaluated interactions or independent incremental risk for coronary and thoracic aortic calcification (TAC). The independent predictive value of TAC for CHD events is not well-established. METHODS: This study used risk factor and computed tomography scan data from 6807 participants in the multi-ethnic study of atherosclerosis (MESA). Using the same images for each participant, TAC and CAC were each computed using the Agatston method. The study subjects were free of incident CHD at entry into the study. RESULTS: The mean age of the study population (n=6807) was 62±10 years (47% males). At baseline, the prevalence of TAC and CAC was 28% (1904/6809) and 50% (3393/6809), respectively. Over 4.5±0.9 years, a total of 232 participants (3.41%) had CHD events, of which 132 (1.94%) had a hard event (myocardial infarction, resuscitated cardiac arrest, or CHD death). There was a significant interaction between gender and TAC for CHD events (p<0.05). Specifically, in women, the risk of all CHD event was nearly 3-fold greater among those with any TAC (hazard ratio: 3.04, 95% CI: 1.60-5.76). After further adjustment for increasing CAC score, this risk was attenuated but remained robust (HR: 2.15, 95% CI: 1.10-4.17). Conversely, there was no significant association between TAC and incident CHD in men. In women, the likelihood ratio chi square statistics indicate that the addition of TAC contributed significantly to predicting incident CHD event above that provided by traditional risk factors alone (chi square=12.44, p=0.0004) as well as risk factors+CAC scores (chi square=5.33, p=0.02). On the other hand, addition of TAC only contributed in the prediction of hard CHD events to traditional risk factors (chi-square=4.33, p=0.04) in women, without contributing to the model containing both risk factors and CAC scores (chi square=1.55, p=0.21). CONCLUSION: Our study indicates that TAC is a significant predictor of future coronary events only in women, independent of CAC. On studies obtained for either cardiac or lung applications, determination of TAC may provide modest supplementary prognostic information in women with no extra cost or radiation.

Effects of lipid-altering therapies on ventricular arrhythmias and sudden cardiac death.

Sudden cardiac death remains a leading cause of mortality in the United States, with an incidence of 300,000 to 400,000 deaths annually. Despite advances in the management of cardiovascular disease, the only effective treatments proven to reduce the risk of sudden cardiac death are beta-adrenergic blockers and implantable cardioverter-defibrillators. Antiarrhythmic medications are effective at treating symptomatic and asymptomatic ventricular arrhythmias, but several are associated with increased mortality. Although effective at lowering mortality, implantable cardioverter-defibrillators pose an economic burden and some morbidity to patients when associated with frequent shock therapies. Thus, there is renewed interest in developing additional pharmacologic alternatives that could reduce the risk of fatal ventricular arrhythmias. A post hoc analysis of 2 large clinical trials suggested an association between the use of lipid-altering therapy and decreased rates of sudden death. Retrospective review of other clinical trials and experimental data using animal models provide further insight into the potential antiarrhythmic properties of lipid-altering therapy. This review examines the current status of basic science and clinical research that explores the antiarrhythmic properties of lipid-altering therapy, with a focus on 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and polyunsaturated fatty acids.

Lipid-altering therapy and atrial fibrillation.

Atrial fibrillation (AF) is a common cardiac arrhythmia with significant morbidity and public health cost. Because of limitations of efficacy and safety of conventional antiarrhythmic agents, alternative therapies for AF are needed. The potential antiarrhythmic properties of lipid-altering therapy, including the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and fish oils, are increasingly recognized, particularly in light of their potential anti-inflammatory properties. This review examines the known effects of lipid-altering therapy on atrial arrhythmias in both experimental and clinical settings. Inflammatory states, such as post-cardiac surgery and AF of recent onset, show promise as targets. In contrast, lipid-lowering therapy is less likely to affect longstanding persistent AF. Current recommendations for the use of lipid-altering therapy for prevention and treatment of AF are summarized.

Impact of a community-based multiple risk factor intervention on cardiovascular risk in black families with a history of premature coronary disease.

BACKGROUND: Black subjects with a family history of premature coronary heart disease (CHD) have a marked excess risk, yet barriers prevent effective risk reduction. We tested a community-based multiple risk factor intervention (community-based care [CBC]) and compared it with "enhanced" primary care (EPC) to reduce CHD risk in high-risk black families. METHODS AND RESULTS: Black 30- to 59-year-old siblings of a proband with CHD aged <60 years were randomized for care of BP > or =140/90 mm Hg, LDL cholesterol > or =3.37 mmol/L, or current smoking to EPC (n=168) or CBC (n=196) and monitored for 1 year. EPC and CBC were designed to eliminate barriers to care. The CBC group received care by a nurse practitioner and a community health worker in a community setting. The CBC group was 2 times more likely to achieve goal levels of LDL cholesterol and blood pressure compared with the EPC group (95% CI, 1.11 to 4.20 and 1.39 to 3.88, respectively) with adjustment for baseline levels of age, sex, education, and baseline use of medications. The CBC group demonstrated a significant reduction in global CHD risk, whereas no reduction was seen in the EPC group (P<0.0001). CONCLUSIONS: Eliminating known barriers may not be sufficient to reduce CHD risk in primary care settings. An alternative community care model that addresses barriers may be a more effective way to ameliorate CHD risk in high-risk black families.

Treatment of hyperlipidemia in cardiac transplant recipients.

Of the 60,000 patients receiving heart transplants between 1982 and 2001, approximately 12,000 are currently alive. The high incidence of hyperlipidemia and coronary disease (also known as accelerated graft atherosclerosis, or AGA) in these patients warrants early prophylaxis soon after transplantation with 3-hydroxy-3-methylglutaryl (HMG) Co-A reductase inhibitors (statins). Immunosuppressive agents such as prednisone, cyclosporine, mycophenylate mofetil, and sirolimus are associated with hyperlipidemia. Statins, in addition to lowering cholesterol levels, also benefit cardiac transplant recipients via effects on the immune system and endothelial function. Recent data have demonstrated that statins decrease AGA and mortality rates. Furthermore, greater benefits are seen when statins are started early. The 2 statins shown to decrease mortality in patients after cardiac transplantation are pravastatin and simvastatin, which differ in their metabolism (pravastatin is the only statin with non-cytochrome metabolism) and lipophilicity (pravastatin is less lipophilic). Although the benefit of simvastatin has been shown to extend to 8 years after transplantation, increased adverse effects in other studies with higher doses of simvastatin have resulted in new prescribing recommendations, which state that the dose of simvastatin should probably not exceed 10 mg with cyclosporine or gemfibrozil and 20 mg with amiodarone or verapamil. The evidence for potential benefits, interactions, and adverse effects of other potential lipid-lowering drugs for this patient population, such as fibrates, niacin, fish oil, cholestyramine, and ezetimibe, are also discussed. A summary algorithm is proposed, including approaches to patients with statin-associated musculoskeletal symptoms and patients with inadequate results after initial statin therapy.