Therapeutic Options to Further Lower C-Reactive Protein for Patients on Statin Treatment

Cardiovascular disease remains the leading cause of morbidity and mortality in developed nations. Inflammation plays an increasingly important role in the cardiovascular disease process. Recent statin trials have demonstrated a correlation between the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) and cardiovascular risk. This review describes the results of changes in hsCRP in the major statin outcome trials and the concept of a “dual target” for both low-density lipoprotein cholesterol and hsCRP. The effect on hsCRP of combination statin therapy with ezetimibe, fenofibric acid, niacin, and colesevelam is reviewed. Although some statin combination therapies have additional effects on CRP and other atherogenic lipids, evidence for their effect on cardiovascular risk beyond statin monotherapy is lacking. Ongoing placebo-controlled trials investigating statin combination therapy versus statin monotherapy may provide additional clues to the role of additional changes in lipids versus markers of inflammation on cardiovascular risk reduction. Until these trials are completed, current evidence suggests focusing on low-density lipoprotein cholesterol targets.     

Key questions resulting from the JUPITER trial assessing cardiovascular disease intervention with rosuvastatin

THIS PAPER PRESENTS AN ANALYSIS OF THE RECENTLY PUBLISHED JUSTIFICATION FOR THE USE OF STATINS IN PREVENTION (JUPITER: an intervention trial evaluating rosuvastatin) trial, which tested the statin rosuvastatin in apparently healthy individuals with no prior cardiovascular (CVD) disease and with normal plasma low density lipoprotein (LDL) cholesterol concentrations but with raised plasma high sensitivity C-reactive protein (hsCRP) levels. The rate of the combined primary CVD endpoint was significantly reduced in the treatment arm after a median of under 2 years. The JUPITER trial is distinct from previous studies examining statin use in primary prevention groups because the target group for drug therapy was apparently healthy men and women at low or intermediate risk for developing CVD. On the basis of JUPITER's findings, there are key questions that should be assessed on the therapeutic intervention of CVD regarding: the primary prevention groups that should be targeted for statin therapy, the utility of targets in addition to plasma LDL cholesterol levels, and the need to consider the metabolic state of individuals targeted for therapy (including the presence of obesity and inflammation). The conclusion from the current analysis is that the JUPITER results warrant further LDL cholesterol lowering than is currently targeted in primary prevention groups that have a pre-existing condition or lifestyle that elevates CVD risk but still do not have a high global CVD risk (as assessed with current algorithms). This group is not captured in current widely used CVD risk calculations, however, with the identification of useful biomarkers, such as hsCRP, this group can be better identified and targeted for intervention.     

Low HDL-C: a secondary target of dyslipidemia therapy

Current guidelines for the prevention of coronary heart disease (CHD) focus on lowering low-density lipoprotein cholesterol (LDL-C) as the primary target of lipid-modifying therapy. However, there is increasing interest in high-density lipoprotein cholesterol (HDL-C) as a secondary target of therapy. A wealth of epidemiologic data demonstrate that low levels of HDL-C are associated with an increased risk of CHD events, and data from large-scale clinical trials with statins and fibrates indicate that observed clinical benefits are related, at least in part, to improvements in HDL-C levels. Raising HDL-C levels with therapeutic lifestyle changes and pharmacologic intervention might afford opportunities to further reduce the risk of CHD beyond LDL-C lowering. Statins are first-line pharmacotherapy for dyslipidemia and can also improve HDL-C levels, although the extent to which they modify HDL-C varies. Combining a fibrate or niacin with statin therapy raises HDL-C more than a statin alone but might be associated with reduced tolerability and increased adverse reactions. Several new therapeutic approaches to raising HDL-C are in development, including an HDL mimetic and inhibitors of cholesteryl ester transfer protein. Although lowering LDL-C remains the primary target of lipid-modifying therapy, dyslipidemia therapies that are efficacious for both LDL-C reduction and raising HDL-C might offer further improvements in CHD risk reduction.     

Monotherapy vs combination therapy for dyslipidemia in the elderly

Dyslipidemia conveys a major increased risk of future cardiovascular events in older persons. Data from large randomized controlled trials confirm that statin therapy is as beneficial in older adults as it is in younger persons in both primary and secondary prevention. National guidelines support the use of statin therapy to reduce low-density lipoprotein cholesterol in older adults, with the recommended goal of <100 mg/dL in high-risk patients and an optional goal of <70 mg/dL in very high-risk patients. In the majority of high-risk older patients, these levels of low-density lipoprotein cholesterol can be achieved with initial low doses of an efficacious statin, but in some clinical situations, combination therapy may be considered. Moreover, statins appear to be safe and well tolerated in older age groups. Because of heightened risks of drug-drug interactions, the likelihood of polypharmacy in seniors, and issues of tolerability and convenience, monotherapy with low doses of an efficacious statin may be preferable to combination therapy in elderly individuals.     

Clinical and Biological Relevance of Statin-Mediated Changes in HDL Metabolism

Although prospective studies consistently show that individuals with low levels of high-density lipoprotein (HDL) cholesterol are at increased cardiovascular risk, it is still not clear whether or not this relationship still holds in patients treated with statins who have achieved optimal low-density lipoprotein cholesterol levels. Additionally, the hypothesis that statin-mediated increases in HDL cholesterol levels have a impact on cardiovascular risk has not been clearly demonstrated. Statin therapy has little impact on the cholesterol content carried by HDL in the bloodstream (i.e., HDL cholesterol levels), but statins can induce a significant redistribution of HDL particle size, particle concentration, and physicochemical and functional properties. Our objective is to summarize the evidence arising from epidemiological, clinical, and experimental studies that suggests a potential role for statin therapy in the modulation of parameters of HDL metabolism and reverse cholesterol transport.     

Cost-effectiveness of cholesterol-lowering therapies according to selected patient characteristics

BACKGROUND: The National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II) recommends treatment guidelines based on cholesterol level and number of risk factors. OBJECTIVE: To evaluate how the cost-effectiveness ratios of cholesterol-lowering therapies vary according to different risk factors. DESIGN: Cost-effectiveness analysis. DATA SOURCES: Published data. TARGET POPULATION: Women and men 35 to 84 years of age with low-density lipoprotein cholesterol levels of 4.1 mmol/L or greater (> or =160 mg/dL), divided into 240 risk subgroups according to age, sex, and the presence or absence of four coronary heart disease risk factors (smoking status, blood pressure, low-density lipoprotein cholesterol level, and high-density lipoprotein cholesterol level). TIME HORIZON: 30 years. PERSPECTIVE: Societal. INTERVENTIONS: Step I diet, statin therapy, and no preventive treatment for primary and secondary prevention. OUTCOME MEASURES: Incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: Incremental cost-effectiveness ratios for primary prevention with step I diet ranged from $1900 per quality-adjusted life-year (QALY) gained to $500000 per QALY depending on risk subgroup characteristics. Primary prevention with a statin compared with diet therapy was $54000 per QALY to $1400000 per QALY. Secondary prevention with a statin cost less than $50000 per QALY for all risk subgroups. RESULTS OF SENSITIVITY ANALYSIS: The inclusion of niacin as a primary prevention option resulted in much less favorable incremental cost-effectiveness ratios for primary prevention with a statin (>$500000 per QALY). CONCLUSIONS: Cost-effectiveness of treatment strategies varies significantly when adjusted for age, sex, and the presence or absence of additional risk factors. Primary prevention with a step I diet seems to be cost-effective for most risk subgroups but may not be cost-effective for otherwise healthy young women. Primary prevention with a statin may not be cost-effective for younger men and women with few risk factors, given the option of secondary prevention and of primary prevention in older age ranges. Secondary prevention with a statin seems to be cost-effective for all risk subgroups and is cost-saving in some high-risk subgroups.     

C-reactive protein, statins, and the primary prevention of atherosclerotic cardiovascular disease

Emerging data implicate inflammation as integral to atherosclerosis and its complications. From a clinical perspective, the inflammatory biomarker C-reactive protein has demonstrated consistent predictive value in the detection of individuals at high risk for cardiovascular disease. Therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduces C-reactive protein as well as low-density lipoprotein cholesterol, thus providing a potential additional mechanism for the reduction in cardiovascular events associated with the use of these agents. Evidence from the Air Force/Texas Coronary Atherosclerosis Prevention Study suggests that statin therapy may be effective in reducing incident coronary events among those with elevated levels of C-reactive protein but normal levels of low-density lipoprotein cholesterol. These data, along with accumulating laboratory data, support a potential anti-inflammatory benefit of statins. Large-scale, randomized trials in the primary prevention of acute coronary events among individuals without overt hyperlipidemia but with evidence of elevated C-reactive protein are now needed to directly test this hypothesis.     

Genetic polymorphisms in emerging cardiovascular risk factors and response to statin therapy

Current strategies for both the primary and secondary prevention of coronary heart disease (CHD) focus on the traditional risk factors, such as hypertension, smoking cessation, and cholesterol, as the primary determinants of the cardiac risk profile, with particular emphasis on the reduction of low-density lipoprotein cholesterol (LDL-C) to targeted goal levels as endorsed by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII). Large primary and secondary prevention trials with the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated varying reductions in cardiovascular events associated with similar changes in LDL-C levels, suggesting statins may possess additional beneficial effects on other risk factors.Retrospective analyses of many statin trials have evaluated the association between several polymorphic candidate genes (apolipoprotein E, stromelysin-1, -fibrinogen, cholesteryl ester transfer protein, lipoprotein lipase, hepatic lipase, and platelet glycoprotein III) which have been identified as predictors of disease severity and both metabolic and clinical response to statin therapy. These results suggest that statin therapy improves plasma lipid profiles in all patients, but preferentially benefits individuals who carry a high risk, variant genotype for these risk factors as compared to individuals with the wild-type genotype. These observations suggest that determining individual patient genotype may be useful in optimizing the benefits of statin therapy. These hypothesis-generating data need to be prospectively evaluated in genotyped patients.     

C-reactive protein is not associated with the presence or extent of calcified subclinical atherosclerosis

BACKGROUND: Both high-sensitivity C-reactive protein (hsCRP) and electron beam computed tomography (EBCT) coronary artery calcification (CAC) are valid markers of cardiovascular risk. It is unknown whether hsCRP is a marker of atherosclerotic burden or whether it reflects a process (eg, inflammatory fibrous cap degradation) leading to acute coronary events. METHODS: A nested case-control study was performed of 188 men enrolled in the Prospective Army Coronary Calcium study. The serum hsCRP levels (latex agglutination assay) were evaluated in subjects with CAC (CAC score >0, n = 94) and compared with age- and smoking status-matched control subjects (CAC score 0, n = 94). RESULTS: Levels of hsCRP in the highest quartile were related to the following coronary risk factors: smoking status, low-density lipoprotein cholesterol, body mass index, glycosylated hemoglobin, fibrinogen, and homocysteine. The mean hsCRP level was similar in cases (+CAC, 0.20 +/- 0.22 mg/dL) and controls (-CAC, 0.19 +/- 0.21 mg/dL; P =.81) and was unrelated to the log-transformed CAC score (r < 0.01, P =.91). Multivariable analysis controlling for standard risk factors, aspirin, and statin therapy found only that low-density lipoprotein cholesterol was related to CAC. CONCLUSIONS: Despite associations with standard and emerging cardiovascular risk factors, hsCRP is unrelated to the presence and extent of calcified subclinical atherosclerosis. This implies that CAC (a disease marker) and hsCRP (a process marker) may be complementary for the prediction of cardiovascular risk.     

JUPITER and satellites: Clinical implications of the JUPITER study and its secondary analyses

The justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin(JUPITER) study was a real breakthrough in primary cardiovascular disease prevention with statins,since it was conducted in apparently healthy individuals with normal levels of low-density lipoprotein cholesterol(LDL-C <130 mg/dL)and increased inflammatory state,reflected by a high concentration of high-sensitivity C-reactive protein(hs-CRP≥2 mg/L).These individuals would not have qualified for statin treatment according to current treatment guidelines.In JUPITER,rosuvastatin was associated with significant reductions in cardiovascular outcomes as well as in overall mortality compared with placebo.In this paper the most important secondary analyses of the JUPITER trial are discussed,by focusing on their novel findings regarding the role of statins in primary prevention.Also,the characteristics of otherwise healthy normocholesterolemic subjects who are anticipated to benefit more from statin treatment in the clinical setting are discussed.Subjects at"intermediate"or"high"10-year risk according to the Framingham score,those who exhibit low post-treatment levels of both LDL-C(< 70 mg/dL)and hs-CRP(<1 mg/L),who are 70 years of age or older,as well as those with moderate chronic kidney disease(estimated glomerular filtration rate <60 mL/min every 1.73 m2)are anticipated to benefit more from statin treatment.Unlikely other statin primary prevention trials,JUPITER added to our knowledge that statins may be effective drugs in the primary prevention of cardiovascular disease in normocholesterolemic individuals at moderate-to-high risk.Also,statin treatment may reduce the risk of venous thromboembolism and preserve renal function.An increase in physician-reported diabetes represents a major safety concern associated with the use of the most potent statins.     

Can intensive statin therapy halt the progression of atherosclerosis? Recent evidence and potential implications for patient management

A number of studies using various imaging techniques have demonstrated that intensive lipid lowering with statins can halt or delay the progression of atherosclerosis and even, in some cases, lead to plaque regression. Improvements in atheroma burden with intensive statin therapy appear to be related not just to decreasing low-density lipoprotein cholesterol but also to anti-inflammatory and antiproliferative effects. Clinical trial results also suggest that achieving low-density lipoprotein cholesterol levels even lower than those currently recommended can produce improved clinical outcomes across a range of patient types. Given this body of evidence, it appears appropriate to use intensive statin therapy to treat dyslipidemic patients at high risk for coronary heart disease.     

Baseline characteristics of participants in the JUPITER trial, a randomized placebo-controlled primary prevention trial of statin therapy among individuals with low low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein

The Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) is a randomized, double-blind, placebo-controlled primary prevention trial of statin therapy among persons with average to low levels of low-density lipoprotein (LDL) cholesterol who are at increased cardiovascular risk due to elevated plasma concentrations of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP). A total of 17,802 persons with LDL cholesterol<130 mg/dl (3.36 mmol/L) and hs-CRP>or=2 mg/L were recruited from 26 countries and randomly allocated to 20 mg/day rosuvastatin or placebo. In contrast to previous studies of statin therapy in primary prevention, JUPITER is evaluating a group with modest plasma concentrations of LDL cholesterol (median 108 mg/dl, interquartile range 94 to 119). Further, the trial includes 6,801 women (38.2%) and 5,577 participants with metabolic syndrome (32.1%). Thus, in addition to broadening our understanding of statin therapy and inflammation, the JUPITER trial will provide important and clinically relevant information on primary prevention among patients who do not currently qualify for lipid-lowering therapy. In conclusion, as 20 mg of rosuvastatin can reduce LDL cholesterol by up to 50%, JUPITER will also provide crucial safety data for several thousand patients who should achieve LDL cholesterol levels<50 mg/dl on a long-term basis.     

Magnitude and characteristics of residual lipid risk in patients with a history of coronary revascularization: the ICP-bypass study

Introduction and objectives

Residual lipid risk has been defined as the excess of cardiovascular events observed in patients with adequate control of low-density lipoprotein cholesterol and has been mainly attributed to high-density lipoprotein cholesterol and triglycerides. The aim of our study was to describe the clinical features and the magnitude and characteristics associated with residual lipid risk in patients with a history of coronary revascularization.

Methods

Multicenter, observational, cross-sectional study of patients with a history of coronary revascularization. Residual lipid risk was defined as the presence of high-density lipoprotein cholesterol <40 mg/dL and/or triglycerides >150 mg/dL in patients with low-density lipoprotein cholesterol <100 mg/dL.

Results

We included 2292 patients with a mean age of 65.5 (12.4) years; 94.1% were receiving no statin therapy and 4.8% no lipid therapy. Statin-only therapy (74%) was the most common strategy, followed by combination with ezetimibe (17%). The prevalence of high-density lipoprotein cholesterol <40 mg/dL was 35.8%, hypertriglyceridemia 38.9%, and low-density lipoprotein cholesterol >100 mg/dL 44.9%; the residual lipid risk group included 29.9% of all patients. This patient group had a similar clinical profile except for slightly lower mean age, higher incidence of diabetes, and higher proportion of men. Multivariate analysis identified positive associations of diabetes and male sex with residual lipid risk; current smoking, male sex, and fibrate therapy were associated with high-density lipoprotein cholesterol <40 mg/dL; current smoking, abdominal obesity, and fibrate therapy were associated with hypertriglyceridemia.

Conclusions

In daily clinical practice, almost one-third of patients with a history of coronary revascularization have low-density lipoprotein cholesterol <100 mg/dL plus low high-density lipoprotein cholesterol and/or hypertriglyceridemia, a concept known as residual lipid risk.Full English text available from: www.revespcardiol.org     

The pravastatin inflammation CRP evaluation (PRINCE): rationale and design

BACKGROUND: Randomized, controlled trials demonstrate that HMG CoA reductase inhibition reduces coronary event rates in both primary and secondary prevention. In addition to reducing cholesterol levels, laboratory evidence suggests that statins also have anti-inflammatory activity, a property that may be critical for maintaining plaque stability. Recently, the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) has been shown to predict vascular risk in individuals with and without hyperlipidemia. Furthermore, in the Cholesterol and Recurrent Events (CARE) trial, the relative efficacy of pravastatin in reducing events was greatest among those with elevated levels of hs-CRP. However, the time course and magnitude of this effect in both primary and secondary prevention is controversial. METHODS: PRavastatin Inflammation CRP Evaluation (PRINCE) is an investigator-initiated, multicenter, community-based trial that will evaluate the effects of pravastatin on hs-CRP in up to 1182 individuals with coronary artery disease and up to 1702 individuals without coronary artery disease. Lipid profiles and hs-CRP levels will be obtained at baseline, 12 weeks, and 24 weeks in all study participants. Patients with known coronary artery disease will receive 40 mg/d pravastatin, whereas those without coronary artery disease will be randomly assigned to receive placebo or 40 mg/d pravastatin. CONCLUSIONS: The potential clinical impact of the PRINCE trial is substantial because nearly 50% of myocardial infarctions in the United States occur in persons with normal cholesterol levels, and inflammatory markers such as hs-CRP may provide a means to detect such individuals at high risk who do not currently qualify for statin therapy. The PRINCE trial will determine the time course of effect of this statin on hs-CRP and whether any observed effect on hs-CRP is independent of pravastatin-induced changes in low-density lipoprotein cholesterol.     

Niacin-ER/statin combination for the treatment of dyslipidemia: focus on low high-density lipoprotein cholesterol

Statins are effective drugs for lowering low-density lipoprotein cholesterol, and their use has been associated with a significant decrease in cardiovascular morbidity and mortality. However, statins are ineffective in lowering plasma triglycerides and lipoprotein(a), or increasing low high-density lipoprotein cholesterol (HDL-C) plasma levels, which are independent risk factors for coronary heart disease. Niacin, on the other hand, is the most potent drug available for lowering plasma levels of triglycerides and lipoprotein(a) and raising HDL-C levels. It follows, then, that a combination of niacin with a statin might be an effective combination in improving all components of the lipid profile. Previous studies have shown that the use of long-acting niacin with a statin, in dose combinations of niacin-ER/lovastatin 1000/20 mg or 2000/40 mg once daily, has been effective in favorably modifying low-density lipoprotein cholesterol, triglycerides, lipoprotein(a), and HDL-C plasma levels. Dyslipidemias often predate the onset of hypertension, and HDL-C has been found to be inversely related to the incidence of hypertension. Normalization of lipid components, including the total cholesterol/HDL-C ratio, is important in the management of hypertensive individuals and patients with the metabolic syndrome or diabetes. Thus, the long-term treatment of dyslipidemias with these two agents may help to modify risk and reduce cardiovascular morbidity and mortality in these patients over and above benefits achieved by lowering blood pressure     

Fibrates in combination with statins in the management of dyslipidemia

While elevated low-density lipoprotein cholesterol is the primary target of hypercholesterolemia treatment, high triglycerides and low high-density lipoprotein cholesterol are also important targets for therapy. Correcting these lipid abnormalities should be an integral part of therapy in hypertensive individuals. Medications such as the fibrates are effective and well tolerated for reducing triglycerides and increasing high-density lipoprotein cholesterol, and their use has resulted in a reduction in cardiovascular events. Fibrates are also recommended as adjunct therapy for patients receiving statins whose low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol is not reduced to goal levels. The combination of a statin and a fibrate may, however, raise the risk of myopathy and rhabdomyolysis. Gemfibrozil, one of the fibrates, but not fenofibrate, interferes with statin glucuronidation, which may increase the risk of myopathy due to elevations in statin serum levels. This may at least partially explain the lower incidence of myopathy with fenofibrate compared with gemfibrozil when combined with statins. Combination therapy with a fibrate and a statin is a potentially useful therapy for patients with atherogenic lipid profiles, for which fenofibrate appears to be a more appropriate choice due to less myopathic potential.     

Reducing the Threshold of Primary Prevention of Cardiovascular Disease to 10% Over 10 Years: The Implications of Altered Intensity “Statin” Therapy Guidance

Cardiovascular disease (CVD) is a significant noncommunicable disease associated with high long-term mortality. In addition to more effective secondary therapies, the primary prevention of CVD has developed markedly in the past several years. This study aims to investigate the evidence and impact of reducing the threshold for primary CVD risk management to 10% over 10 years with “statin” therapy. To conduct research a systematic review utilizing 5 electronic database searches was completed for studies, analyzing the clinical effect of reducing the threshold of CVD risk to 10% over 10 years for primary prevention with statin therapy. The study included six (6) trials. Statin therapy was allocated to 31,018 participants. The mean age was 61 years and the mean follow-up was 4.6 years. The mean relative reduction in total cholesterol was 19% (from an average of), low-density lipoprotein cholesterol was 28.3% (from mmol/L to mmol/L) and triglycerides were 14.8% (from mmol/L to mmol/L). High-density lipoprotein cholesterol was observed to increase by a mean of 3.3% (from mmol/L to mmol/L). When examining all-cause mortality, statin therapy was associated with a 12% relative risk reduction compared with control, where overall rates were reduced from 1.4% to 1. % There is a 30% risk reduction in general major coronary events (from to %). There is a 19% risk reduction in general major cerebrovascular events with the statin group. While there is undoubtedly statistical evidence that supports the observation of the effectiveness of statin therapy for primary prevention, there is a risk that many hundreds of patients need to be treated to avoid a single adverse clinical outcome.     

Beyond the Statins: New Therapeutic Perspectives in Cardiovascular Disease Prevention

Reduction of low-density lipoprotein cholesterol (LDL-C) with statin therapy is currently identified in treatment guidelines as the primary focus for patients with or at risk of coronary heart disease (CHD). Yet despite effective statin therapy there is still an unacceptably high residual coronary risk. A substantial proportion of patients with CHD have mixed dyslipidemia, including low levels of high-density lipoprotein cholesterol (HDL-C), an independent and predictive risk factor for CHD. Although effective in reducing LDL-C, statin therapy has only modest effects in raising HDL-C. Fibrate therapy is an alternative lipid-modifying strategy, and is effective in reducing CHD mortality and morbidity, with the magnitude of clinical benefit similar to statin therapy. Multi-drug therapy with complementary mechanisms of action has been proposed as a means of improving lipid-modifying efficacy. Nicotinic acid is the most potent agent for increasing HDL-C and also substantially reduces LDL-C and triglycerides. Addition of nicotinic acid to statin therapy would be a logical management approach, given the potential for complementary therapeutic benefit. The clinical benefits of this combination are supported by the results of the HDL Atherosclerosis Treatment Study, which showed reduction of 60–90% in the incidence of major coronary events when both agents were administered. In addition, combination treatment led to angiographic regression of stenosis, compared with placebo, rather than slowed progression as previously reported with statin monotherapy. Given that the prevalence of low HDL-C, particularly amongst individuals with CHD, is higher than previously anticipated, combining nicotinic acid and a statin represents an innovative approach to further reducing CHD risk.This review paper was funded by an unrestricted educational grant form Merck KgaA, Darmtadt, Germany.     

In-hospital initiation of statin therapy in acute coronary syndromes: maximizing the early and long-term benefits

Patients with acute coronary syndrome (ACS) are at high risk for recurrent coronary events, sudden death, and all-cause mortality. Conventional revascularization therapies reduce the risk of further ischemia but do not affect the underlying atherosclerotic disease. Statins have a proven record in the secondary prevention of coronary heart disease. Furthermore, statins have been shown to exert varying degrees of pleiotropic effects, which may stabilize vulnerable atherosclerotic plaques. A compelling body of evidence from randomized controlled trials demonstrates that high-dose, potent statin therapy initiated immediately after an acute coronary event can significantly reduce early as well as longer-term morbidity and mortality. Furthermore, high-dose, potent statin therapy displays a reasonable safety profile. National guidelines now recommend that in patients with ACS, statin therapy should be initiated in hospital prior to discharge, irrespective of baseline low-density lipoprotein cholesterol levels, to improve clinical outcomes. Every effort should be made to ensure all eligible patients with ACS are initiated and maintained on statin therapy.     

Dyslipidemia in type 2 diabetes mellitus

Cardiovascular disease is a significant cause of morbidity and mortality in patients with diabetes mellitus (DM). DM is now recognized as a risk equivalent for coronary heart disease. The lipid profile in patients with type 2 DM is characterized by elevated triglycerides, low levels of high-density lipoprotein cholesterol, and small dense low-density lipoprotein cholesterol (LDLC) particles and is believed to be a key factor promoting atherosclerosis in these patients. Both primary and secondary prevention studies have provided ample evidence that aggressive statin therapy reduces cardiovascular end points in patients with DM. In all persons with DM, current treatment guidelines recommend reduction of LDLC to less than 100 mg/dL, regardless of baseline lipid levels. Lowering LDLC to less than 70 mg/dL may provide even greater benefits, particularly in very high risk patients with DM and coronary heart disease.