Management of selected lipid abnormalities: hypertriglyceridemia, isolated low HDL-cholesterol, lipoprotein(a), and lipid abnormalities in renal diseases and following solid organ transplantation

Although the focus in treating lipid disorders is on reducing LDL-C levels, additional lipid-related independent risk factors, such as TG, HDL-C, and Lp(a) levels, should be used clinically to assess cardiovascular risk. Decisions to initiate drug therapy for LDL-C reduction may be influenced by levels of these other lipoprotein fractions. Data supporting intervention to modify these factors are less abundant than for LDL-C reduction, but in certain circumstances. drug therapy targeted at TGs or HDL-C may be appropriate. Patients who have nephrotic syndrome and end-stage renal disease are at particularly high risk for the development of CVD and should be treated aggressively for their lipid disorders. Finally, solid organ transplant recipients are almost always hyperlipidemic and appropriate therapy could reduce cardiovascular events.     

Indications for lowering LDL cholesterol in rheumatoid arthritis: an unrecognized problem

OBJECTIVE: To evaluate the prevalence of patients with rheumatoid arthritis (RA) in whom lowering low density lipoprotein cholesterol (LDL-C) should be considered in accord with the ATPIII guidelines. The treatment goals are based on the number of risk factors (RF) other than LDL-C. The goal for 0-1 RF is < 160 mg/l, for multiple RF < 130 mg/l, and < 100 mg/l for coronary heart disease (CHD) or CHD risk equivalent (other clinical atherosclerotic diseases and diabetes mellitus). METHODS: A cross-sectional study was conducted in 145 patients with RA. We recorded the patients' characteristics, the potential risk factors for CHD, and results of lipid profile tests [total cholesterol (TC), high density lipoprotein cholesterol, and LDL-C]. RESULTS: Of the 145 patients recruited, 23 had LDL-C lowering therapy. Of the remaining 122 patients (mean age 54 +/- 15 years), of whom 101 (83%) were women, 109 were taking a disease modifying antirheumatic drug. At the time of the study, disease duration was 12 +/- 10 years. Twenty-seven (22%) of the 122 patients needed lowering of LDL-C. If RA was considered as an additional risk factor or a major risk factor, like diabetes mellitus, 35 patients (29%) and 86 (70%) patients, respectively, needed lowering therapy. CONCLUSION: Our study shows the high percentage of patients with RA for whom LDL-C intervention should be considered. As cardiovascular morbidity and mortality is increased in patients with RA, it would be useful to determine whether RA should be considered as an independent cardiovascular risk factor or as a major risk factor like diabetes that warrants more aggressive cardiac prevention measures.     

The role of ezetimibe in the prevention of cardiovascular disease: Where do we stand after ARBITER 6-HALTS

Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, rapidly became one of the most widely drugs in the US following its approval by the FDA in 2002. Due to its capacity to significantly lower LDL-C with few side effects, ezetimibe has been very useful in enabling patients who were statin intolerant to reach their recommended therapeutic goal for LDL-C. In addition, ezetimibe also reduces non-HDL-C and raises HDL-C, further enhancing its effectiveness in clinical practice. A significant preponderance of evidence supports the reduction of LDL-C and non-HDL-C as the most effective therapy to prevent or reverse atherosclerotic cardiovascular disease (ASCVD). However 3 recent clinical trials, ENHANCE, SEAS, and ARBITER 6-HALTS have raised questions about the efficacy and safety of ezetimibe and have led to a re-examination of its clinical use as a drug for managing lipid risk factors to prevent or manage ASCVD. An in-depth analysis of these three trials reveals methodological deficiencies and concerns with the statistical methods used which significantly diminish their indictment of the clinical utility of ezetimibe. In contrast, The SANDS trial has confirmed the effectiveness of ezetimibe in managing both LDL-C and non-HDL-C, and also demonstrated this drug’s ability to improve carotid atherosclerosis by producing regression of CIMT. One of the important conclusions of the SANDS Trail is that ezetimibe remains an effective adjunctive medication for use in patients who do not reach their LDL-C goals on statin monotherapy. However, as a significant residual risk for ASCVD remains even after aggressive goals for LDL-C and non-HDL-C are reached, current treatment strategies should emphasize managing of all cardiac risk factors and increasing HDL in addition to the attainment and maintenance of recommended goals for LDL-C and non-HDL-C. Hence, ezetimibe should be considered as an important component of broad-spectrum management of lipid risk factors with therapy that includes statins, niacin, bile acid sequestrants, fibrates and Omega 3 fatty acids in appropriate combinations in addition to therapeutic life change.     

Therapy to reduce risk of coronary heart disease

Recent primary and secondary intervention studies have shown that reduction of low-density lipoprotein cholesterol (LDL-C) with statins significantly reduced coronary heart disease (CHD) morbidity and mortality. However, many patients with dyslipidemia who have or are at risk for CHD do not reach target LDL-C goals. The recently updated National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines identify a group of patients at very high risk for CHD for more aggressive LDL-C reduction and reaffirm the importance of high-density lipoprotein cholesterol (HDL-C) by raising the categorical threshold to 40 mg/dl. Lipid-lowering therapy needs to be more aggressive in both primary and secondary prevention settings, and therapy should be considered to increase HDL-C as well as lower LDL-C in order to improve patient outcomes. Both combination therapy and the next generation of statins may provide improved efficacy across the dyslipidemia spectrum.     

Major CHD risk factors predominate among African-American women who are eligible for lipid-lowering drug therapy under the new ATP III guidelines.

BACKGROUND: Coronary heart disease remains the leading cause of morbidity and death among African-Americans. We studied the cardiovascular risk factor distributions among African-American men and women deemed eligible for lipid-lowering treatment under the new Adult Treatment Panel Guidelines (ATPIII). DESIGN AND METHODS: A sub-sample of African-American NHANES III subjects aged 20-79 years, with known cardiovascular risk factors and LDL-C levels was identified (n=4,213). We assessed their eligibility for drug therapy using the new ATP III criteria and compared CHD risk factor distributions across gender. Both conservative and drug-optional LDL-C target levels were applied. RESULTS: An estimated 5.7 million African-Americans aged 20-79 are eligible for drug therapy under ATP III, and the overall eligibility prevalence is 24.3%; 47.8% are males and 52.2% are females (P<0.001). Of these, 1.87 million are eligible based on drug-optional LDL-C targets and 54.5% of these are female. Of treatment-eligible individuals, 61% of males versus 72% of females exhibited LDL-C > or =160 mg/dl (P=0.0001). The prevalence and levels of important CHD risk factors such as diabetes, hypertension, mean total and LDL-C cholesterol levels, and body mass index were all greater for eligible females compared to males despite lower absolute Framingham risk estimates for females. CONCLUSIONS: Among African-Americans, more women than men are eligible for treatment under the new ATP III guidelines. Eligibility in women is based primarily on diabetes and lipid levels rather than absolute Framingham risk, which seems to be underestimated in African-American women. As compensation for this underestimate, drug-optional (lower) targets should be applied to this population.     

Prospective association between low and high total and low-density lipoprotein cholesterol and coronary heart disease in elderly men

OBJECTIVES: To examine the relationship between total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and the incidence of coronary heart disease (CHD) in elderly men. DESIGN: Prospective. SETTING: Population based. PARTICIPANTS: A sample of 2,424, Japanese-American men aged 71 to 93 was used. MEASUREMENTS: Six years of data on incident fatal plus nonfatal CHD were examined. RESULTS: Analysis revealed a significant U-shaped relationship between age-adjusted CHD rates and both TC and LDL-C. The ranges of TC and LDL-C with the lowest risk of CHD were 200 to 219 mg/dL and 120 to 139 mg/dL, respectively. As cholesterol concentrations declined and increased beyond these ranges, the risk of CHD increased. These U-shaped relationships remained significant after adjusting for age and other risk factors. CONCLUSION: The U-shaped associations between TC and LDL-C and CHD imply a complex relationship between lipids and CHD in late life. The results indicate that elevated lipid levels should continue to be treated in healthy elderly individuals, as they are in those who are younger, although pharmacologically lowering lipids to excessively low levels in the elderly may warrant further study, as does the contribution of subclinical frailty to the relationship of lipids to CHD risk.     

Role of lipid and lipoprotein profiles in risk assessment and therapy

Although low-density lipoprotein cholesterol (LDL-C) remains the primary target for coronary heart disease (CHD) prevention in the latest guidelines of the National Cholesterol Education Program, many individuals who have CHD do not have substantially elevated LDL-C but have derangement of other lipid fractions, most commonly low levels of high-density lipoprotein cholesterol (HDL-C). In the guidelines, HDL-C is important in risk stratification in primary prevention, influencing the need for and intensity of treatment of LDL-C, and both HDL-C and triglyceride are defined as risk factors for the metabolic syndrome, a secondary target of therapy. Triglyceride level also determines in which individuals non-HDL-C should be a secondary target of therapy. Risk assessment that takes into account the entire lipid profile will identify more high-risk individuals than evaluating LDL-C alone. Some epidemiologic data suggest that instead of measuring the cholesterol in LDL or HDL, measuring their respective apolipoproteins, apolipoprotein (apo) B-100 and apo A-I, may improve CHD risk assessment, and in some observational and interventional studies, ratios of lipids and/or apolipoproteins have been better predictors of CHD risk than levels of any one lipid fraction. Trials of lipid-modifying therapy also suggest that apolipoproteins and ratios may provide improved targets for therapy beyond LDL-C, but optimal values have not been established. Because lipid-modifying therapy affects multiple components of the lipid profile, the effect on all lipid parameters should be considered when selecting the most appropriate agent. Therapies with beneficial effects across the lipid profile would be expected to improve CHD risk reduction.     

Leitliniengerechte Diagnostik von Dyslipid?mien

Cardiovascular diseases are the main cause of mortality for patients with advanced age. Changes in lipid metabolism are common and play an important role as key risk factors. This article explains an approach in the diagnosticis of dyslipidemia according to the current guidelines. First, the overall risk evaluation of cardiovascular mortality based on the current chart has to be evaluated. Depending on these results an individual LDL-C goal should be defined. The article also includes other relevant cardiovascular risk factors which were not included in the established risk charts. Furthermore, the main innovative biomarkers are discussed in their possible applications and diagnostic value.     

Coronary heart disease prevention in women: focus on lipids

Coronary heart disease (CHD) remains an urgent and leading threat to women's health and well-being. Clinical trials have demonstrated a clear cut benefit of low density lipoprotein cholesterol (LDL-C) lowering in both women as well as men with coronary disease. While the case for primary prevention of CHD with LDL-C lowering is less secure in both men and women, there is little doubt that patients at high risk of CHD, even without a prior history of vascular events, will in the long run benefit from LDL-C lowering. Thus, all available evidence indicates that lipid interventions should be pursued aggressively in both women and men at risk of CHD.     

The air force/texas coronary atherosclerosis prevention study: implications for preventive cardiology in the general adult US population

Atherosclerotic cardiovascular diseases are the most common causes of death in the United States. Fibrous plaques develop in 77% to 78% of men before age 30. The mean low-density lipoprotein-cholesterol (LDL-C) level in men aged 25 to 30 years is 117 mg/dL. In the Air Force/Texas Coronary Atherosclerosis Prevention Study, lovastatin therapy was associated with a 40% reduction in risk of fatal and nonfatal myocardial infarction. The reduction in risk of myocardial infarction was independent of baseline LDL-C level with baseline LDL-C levels as low as 125 mg/dL. The National Cholesterol Education Program guidelines should be simplified by recommending that LDL-C levels be less than 100 mg/dL in all adults in the United States.     

低密度脂蛋白胆固醇与心血管病发病关系的前瞻性研究

目的研究我国人群低密度脂蛋白胆固醇(LDL-C)的分布特征及其与心血管病发病的关系.方法采用前瞻性队列研究方法,对11省市队列人群(35～64岁)共29564人于1992年进行基线调查.对1992～1999年共129350观察人年中发生的心血管病事件进行登记.分析人群基线调查的LDL-C分布特征及其与心血管病发病的关系.结果(1)男女两性LDL-C均值分别为2.65mmol/L和2.70mmol/L(P＜0.01).LDL-C随年龄的增加而升高,女性50～54岁组升高最多;(2)LDL-C超过中位数(2.60mmol/L)时男性缺血性心血管病发病率明显升高;(3)甘油三酯升高(男性≥1.24mmol/L;女性≥1.13mmol/L)合并LDL-C升高者,男女冠心病发病率分别是单纯LDL-C升高者的3倍和2倍;(4)C0x回归显示本研究人群LDL-C每升高1mmol/L可使男性冠心病增加36%,缺血性卒中增加31%.结论我国人群的LDL-C处于较低水平,但LDL-C仍是男性缺血性心血管病(冠心病、缺血性脑卒中)的"独立”危险因素.心血管病防治中不应"独立”地看待某一因素,更应注重多因素的协同作用.     

Residual cardiovascular risk in secondary prevention

Despite substantial progress in the characterization and pharmacological treatment of risk factors associated with cardiovascular disease (CVD), residual cardiovascular risk represents a challenge to an effective CVD primary and secondary prevention. A multifactorial approach aimed at controlling all risk factors present in each individual patient is of paramount importance to effectively reduce the risk of CV events. While aggressive as compared to conventional LDL-cholesterol lowering provides further CV events reduction in secondary prevention patients, significant residual cardiovascular risk remains even after intensive statin therapy and an LDL-C levels of <70?mg/dL. Combination lipid-lowering strategies with a statin and fenofibrate or a statin and nicotinic acid may provide significant residual CV risk reduction in selected subgroups of patients (i.e. patients with diabetes on statin therapy and persistently low HDL-C and/or high triglycerides). Intensive risk factor management approaches aimed at controlling plasma LDL-C, glucose metabolism and blood pressure may significantly reduce residual CV risk; they should however be implemented based on individual cardiovascular risk profiles and clinical phenotypes, following the footsteps of personalized medicine.     

What is the consequence of an abnormal lipid profile in patients with type 2 diabetes or the metabolic syndrome?

Patients with type 2 diabetes have an atherogenic lipid profile, which greatly increases their risk of coronary heart disease (CHD) compared with people without diabetes. The largest disparity in lipid levels among people with and without diabetes occurs for high-density lipoprotein cholesterol (HDL-C) and triglycerides: triglycerides tend to be markedly higher and HDL-C moderately lower in patients with diabetes, in contrast to the negligible difference observed in low-density lipoprotein cholesterol (LDL-C) and total cholesterol. However, patients with type 2 diabetes are more likely to have the atherogenic form of LDL-C than people without diabetes, as well as low HDL-C, which restricts reverse cholesterol transport and may also be associated with increased lipid oxidation. Among patients who have suffered a myocardial infarction, increased LDL-C is apparent in early adulthood, whereas a detectable difference in HDL-C levels becomes increasingly apparent with age and most pronounced after age 60 years, compared with healthy controls. Evidence indicates that the increased risk of macrovascular complications of type 2 diabetes begins long before the onset of clinical hyperglycaemia. Despite successful reduction of LDL-C with statin therapy, patients continue to be at increased risk for CHD if their HDL-C levels remain suboptimal, in part due to persistence of enhanced lipid exchange. Observational data suggest that increasing HDL-C should be much more potent therapeutically than a similar proportionate decrease in LDL-C.     

Lowering LDL cholesterol: questions from recent meta-analyses and subset analyses of clinical trial DataIssues from the Interdisciplinary Council on Reducing the Risk for Coronary Heart Disease, ninth Council meeting

The benefit of cholesterol-lowering therapy in the prevention of coronary heart disease (CHD) is well established. The secondary prevention Scandinavian Simvastatin Survival Study (4S) and the primary prevention West of Scotland Coronary Prevention Study (WOSCOPS) demonstrated that lipid lowering with a statin can dramatically and cost-effectively reduce CHD morbidity and mortality with no increase in noncardiovascular mortality. The Cholesterol and Recurrent Events (CARE) trial extended benefit to CHD patients without high cholesterol. Post hoc analyses of data from these large trials are contributing to speculation, driven by subset analyses and meta-analyses, about whether cholesterol intervention should be target based, as current guidelines recommend. Whereas CARE data support the importance of baseline LDL cholesterol (LDL-C), with greatest clinical event risk reduction in the upper part of the LDL-C range in the trial, 4S found no difference in outcome according to baseline LDL-C in a quartile analysis, and WOSCOPS found no linear relation between decrease in LDL-C and decrease in relative risk for CHD. Furthermore, WOSCOPS showed no additional clinical benefit with LDL-C lowering beyond approximately 24%. Questions raised by such analyses require answers from prospective, hypothesis-based data, and at present there is no compelling argument for moving away from LDL-C targets. The hypothesis-based findings of 4S, CARE, and WOSCOPS support current clinical guidelines, and lowering LDL-C may reduce risk more substantially than might have been predicted.     

The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects

High levels of TSH are associated with an increased cardiovascular risk. Many cardiovascular risk factors cluster within the insulin resistance syndrome. It is not known whether levels of TSH cluster as well. We conducted this research to test the hypothesis that TSH, insulin sensitivity, and levels of low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) are interdependent in euthyroid subjects. Levels of TSH, free thyroid hormone, and serum lipids were measured in fasting serum samples taken before performance of a hyperinsulinemic euglycemic clamp to assess insulin sensitivity in 46 healthy euthyroid subjects with a mean TSH of 1.8 +/- 0.7 mU/L. Significant age- and sex-adjusted partial correlations of TSH with LDL-C (r = 0.48; P < 0.01) and HDL-C (r = -0.36; P < 0.05) were observed. TSH was not significantly correlated with insulin sensitivity or fasting triglyceride concentrations. In line with these results, we found the associations of TSH with LDL-C and HDL-C to be independent of insulin sensitivity. However, we observed significant effect-modification of the association of TSH with LDL-C by insulin sensitivity (P = 0.02). This effect-modification implies a range of associations of TSH with LDL-C that varies from absent in insulin-sensitive subjects to strongly positive in insulin-resistant subjects. We conclude that the increased cardiovascular risk associated with subclinical hypothyroidism seems to extend itself into the normal range of thyroid function. Importantly, the effect-modification of the association of TSH with LDL-C by insulin sensitivity suggests that insulin-resistant subjects are most susceptible to this increased risk.     

Residual cardiovascular risk in secondary prevention

Despite substantial progress in the characterization and pharmacological treatment of risk factors associated with cardiovascular disease (CVD), residual cardiovascular risk represents a challenge to an effective CVD primary and secondary prevention. A multifactorial approach aimed at controlling all risk factors present in each individual patient is of paramount importance to effectively reduce the risk of CV events. While aggressive as compared to conventional LDL-cholesterol lowering provides further CV events reduction in secondary prevention patients, significant residual cardiovascular risk remains even after intensive statin therapy and an LDL-C levels of <70 mg/dL. Combination lipid-lowering strategies with a statin and fenofibrate or a statin and nicotinic acid may provide significant residual CV risk reduction in selected subgroups of patients (i.e. patients with diabetes on statin therapy and persistently low HDL-C and/or high triglycerides). Intensive risk factor management approaches aimed at controlling plasma LDL-C, glucose metabolism and blood pressure may significantly reduce residual CV risk; they should however be implemented based on individual cardiovascular risk profiles and clinical phenotypes, following the footsteps of personalized medicine.     

The benefit of fibrates in the treatment of 'bad HDL-C responders to statins'

BACKGROUND: Lowering high levels of low-density lipoprotein cholesterol (LDL-C) is the primary aim in the prevention of cardiac events. However, low levels of high-density lipoprotein cholesterol (HDL-C) are also associated with an increased risk of ischemic heart disease. Some patients have lower HDL-C during statin treatment than before the treatment. These patients were first described in 2002 as 'bad HDL-C responders to statins'. The aim of this study was to describe the benefit of fibrates in monotherapy for these patients. METHODS: A cross-sectional survey of lipid levels, cardiovascular disease and risk factors in outpatients treated for dyslipidemia. For this study we analyzed the lipid levels, drug treatment and medical history for 14 patients with low HDL-C (<40 mg/dl) during statin treatment and ever treated with fibrates. RESULTS: Total cholesterol (TC) and LDL-C were respectively 8% and 6% higher with fibrates compared to statins. Mean HDL-C was 49% higher during fibrate treatment and TC to HDL-C and LDL-C to HDL-C were respectively 26% and 27% lower with fibrates. CONCLUSIONS: Patients with low levels of HDL-C during statin treatment had far better levels for HDL-C, TC to HDL-C and LDL-C to HDL-C with fibrates in monotherapy. For bad HDL-C responders to statins with low or normal LDL-C treatment with fibrates instead of statins should be considered. For those with high LDL-C fibrates should be added to statins. A randomized double-blind crossover trial with simvastatin and fenofibrate has been initiated to corroborate these findings.     

Management of dyslipidemia in diabetes

Diabetes is associated with a high risk of cardiovascular disease. The management of dyslipidemia, a well-recognized and modifiable risk factor among patients with type 2 diabetes, is an important element in the multifactorial approach to prevent coronary heart disease. Diabetic dyslipidemia typically consists of elevated triglyceride, low high-density lipoprotein cholesterol (HDL-C), and the predominance of small dense low-density lipoprotein (LDL) particles. LDL cholesterol (LDL-C) levels in patients with diabetes are similar to those found in the rest of the population. During the past few years, clinical trials have provided evidence that lipid-lowering therapy has a similar beneficial effect on cardiovascular outcomes in diabetic and nondiabetic individuals. According to current guidelines, the primary lipid target is an LDL-C <100 mg/dL (<70 mg/dL in very high-risk patients) and, to this end, statins are the agents of choice. The appropriate management of dyslipidemia in patients with diabetes, particularly in individuals with low LDL-C, remains controversial. To achieve lipid targets, attention should be directed first toward nonpharmacologic therapeutic interventions to control dyslipidemia, such as diet, exercise, smoking cessation, weight loss, and glycemic control. Statin therapy is recommended for most subjects but, frequently, a combination of lipid-lowering agents is required. A number of combinations are possible, and several factors should be considered to improve the safety of this strategy.     

The evolving role of high-density lipoprotein in reducing cardiovascular risk

In many patients with coronary artery disease, a low level of high-density lipoprotein cholesterol (HDL-C), rather than substantially elevated lowdensity lipoprotein cholesterol (LDL-C), is often the predominant lipid abnormality. Although the National Cholesterol Education Program treatment guidelines include HDL-C concentration as a major risk factor for primary prevention, the guidelines' emphasis on LDL-C as the primary target of therapy may cause uncertainty as to whether risk reduction strategies should focus on lowering LDL-C or raising HDL-C in high-risk patients with low HDL-C. Recent clinical trial evidence and epidemiologic data suggest that HDL-C should play a more important role in risk assessment, and that the definition of low HDL-C may need adjustment from the current National Cholesterol Education Program definition of <35 mg/dL to perhaps <40 mg/dL in men and <45 mg/dL in women. Patients with low HDL-C should receive aggressive risk factor modification, and more emphasis on increasing HDL-C may be warranted in addition to lowering LDL-C.     

Hochdosierte Statintherapie für kardiovaskuläre Risikopatienten

Lowering LDL cholesterol (LDL-C) with statins decreases cardiovascular risk; therefore LDL-C is the primary target in lipid therapy. The amount of risk reduction is the greater, the lower the LDL-C values achieved by statin therapy are. Current guidelines therefore require an LDL-C as low as < 70 mg/dl in patients who are at a very high risk of cardiovascular events. This stringent treatment goal depending on the baseline LDL-C values typically can only be obtained with higher doses of potent statins. Randomised trials demonstrate the efficacy of high-dose therapy with atorvastatin 80 mg/day with regard to the prevention of cardiovascular events in patients after acute coronary syndromes (PROVE-IT TIMI 22 trial), in patients with stable coronary artery disease (TNT trial), and in patients after stroke or TIA (SPARCL trial). Moreover, potent statin treatment reduces the progression of coronary atherosclerosis (REVERSAL and ASTEROID trials). Furthermore, large meta-analyses of the efficacy of high-dose statin therapy confirm its safety; in particular, muscle-related adverse events are not more frequent than with standard statin doses. It is recommended that evidence-based statin doses be used in clinical practice; the dosages used in clinical trials should be given rather than titrating patients to LDL-C targets by increasing statin doses in a stepwise manner. Whether the strong LDL-C lowering combination of simvastatin plus ezetimibe will reduce cardiovascular events over and above simvastatin monotherapy is currently being tested in the ongoing IMPROVE-IT trial. Importantly, despite the large body of evidence in favour of high-dose statin therapy for patients at high cardiovascular risk, high-dose statin therapy is still underused and LDL-C goals are still not met in the majority of these patients.