Treatment of older persons with hypercholesterolemia with and without cardiovascular disease

Hypercholesterolemia is a risk factor for new coronary events in older men and women. Secondary prevention trials have demonstrated in persons with coronary artery disease (CAD) and hypercholesterolemia that statin drugs reduced in older persons all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, and intermittent claudication. Statins have also been shown to slow progression of coronary atherosclerotic plaques in persons with CAD, to reduce restenosis after coronary stent implantation, and to decrease myocardial ischemia in persons with CAD. Older men and women with CAD, prior atherothrombotic brain infarction, peripheral arterial disease, or extracranial carotid arterial disease and a serum low-density lipoprotein (LDL) cholesterol level higher than 125 mg/dl despite diet should be treated with statin drug therapy to lower the serum LDL cholesterol level below 100 mg/dl. Primary prevention trials have shown that statins were also effective in reducing cardiovascular events in older persons with hypercholesterolemia. On the basis of data from the Air Force/Texas Coronary Atherosclerosis Prevention Study, the physician should consider using statins in persons aged 65-80 years without cardiovascular disease with a serum LDL cholesterol level above 130 mg/dl and serum high-density lipoprotein cholesterol level below 50 mg/dl.     

Leitlinien der Lipidtherapie

Alterations in lipid metabolism play a major role in the pathogenesis of atherosclerosis and are an important risk factor for cardiovascular events. Lowering of LDL cholesterol by statins reduces morbidity and mortality in patients with coronary artery disease (CAD), both in primary and secondary prevention. The results of large controlled trials that included more than 50,000 patients are the basis for target values promoted by current guidelines. According to the NCEP-ATP III guidelines LDL cholesterol should be lowered to less than 100 mg/dl in high risk patients (CAD or CAD equivalent) and in very high risk patients optional to less than 70 mg/dl. Up to now even in high risk patients the recommended goals are not sufficiently achieved: Up to 80% of high risk patients do not receive a statin and only a minority of those being treated with a statin have a LDL cholesterol below 100 mg/dl. Furthermore, after a major event (e.g. myocardial infarction) the quality of lipid reduction decreases over time. Further efforts are required to improve this situation as a guide-line oriented approach may help to prevent up to 100,000 myocardial infarctions and deaths alone in high risk patients in Germany.     

Guidelines of lipid therapy translation into clinical practice

Alterations in lipid metabolism play a major role in the pathogenesis of atherosclerosis and are an important risk factor for cardiovascular events. Lowering of LDL cholesterol by statins reduces morbidity and mortality in patients with coronary artery disease (CAD), both in primary and secondary prevention. The results of large controlled trials that included more than 50,000 patients are the basis for target values promoted by current guidelines. According to the NCEP-ATP III guidelines LDL cholesterol should be lowered to less than 100 mg/dl in high risk patients (CAD or CAD equivalent) and in very high risk patients optional to less than 70 mg/dl. Up to now even in high risk patients the recommended goals are not sufficiently achieved: Up to 80% of high risk patients do not receive a statin and only a minority of those being treated with a statin have a LDL cholesterol below 100 mg/dl. Furthermore, after a major event (e.g. myocardial infarction) the quality of lipid reduction decreases over time. Further efforts are required to improve this situation as a guide-line oriented approach may help to prevent up to 100,000 myocardial infarctions and deaths alone in high risk patients in Germany.     

Comparison of Lipid-Lowering Medications and Risk for Cardiovascular Disease in Diabetes

Purpose of the Review

To summarize available evidence regarding lipid-lowering interventions for the prevention of cardiovascular disease in patients with diabetes.

Recent Findings

Statins and non-statin therapies that act through upregulation of LDL receptor expression are associated with similar cardiovascular risk reduction per decrease in LDL cholesterol.

Summary

In subjects with diabetes, with or without established cardiovascular disease, each 39 mg/dl reduction in LDL cholesterol observed with statins is associated with a 21% relative reduction in the risk of major coronary events at 5 years. Statins remain the first-line lipid-lowering agents for the management of dyslipidemia in individuals with diabetes; however, the addition of non-statin therapies to lower LDL cholesterol, such as ezetimibe and PCSK-9 inhibitors, to maximally tolerated statin therapy is recommended in patients with atherosclerotic cardiovascular disease and baseline LDL cholesterol over 70 mg/dl. Recent data support even lower LDL cholesterol targets (<?55 mg/dl) to further reduce the risk of cardiovascular events especially in subjects with diabetes and documented cardiovascular disease.

     

The role of lipid metabolism in the prevention of coronary heart disease

Prevention of cardiovascular disease should be considered as a continuum from low to high risk: those at the highest risk are patients with clinically manifest cardiovascular disease, followed by subjects without known cardiovascular disease at different levels of risk from high to low. Today there is clear evidence that an independent relationship exists between plasma LDL cholesterol levels and the risk for coronary heart disease. The relationship between other plasma lipoproteins and atherosclerosis is more complex. The threshold for individuals requiring LDL cholesterol reduction is determined by epidemiological data, randomized controlled trials, and economic considerations. Patients with familial dyslipidemia suffer early coronary morbidity and mortality. For these patients, consequent lowering of LDL cholesterol should be the primary objective. For patients with established coronary heart disease or other atherosclerotic disease and for those with diabetes, there is significant evidence that reducing LDL cholesterol, irrespective of the initial values, reduces the risk of further coronary events, stroke, and total mortality. For asymptomatic individuals, the treatment of plasma lipids should be based on their absolute coronary risk, including other cardiovascular risk factors. The goals for plasma LDL cholesterol have been set in national and international recommendations. The goals for LDL cholesterol in patients with low, moderate and high coronary risk are <160, <130 and 100 mg/dl, respectively. In some very high risk patients LDL level markedly below 100 mg/dl should be aimed at. HDL cholesterol and triglyceride measurements should be used to identify individuals at high multifactorial risk of cardiovascular disease and used as additional considerations in the selection of lifestyle and drug interventions.     

Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal

The normal low-density lipoprotein (LDL) cholesterol range is 50 to 70 mg/dl for native hunter-gatherers, healthy human neonates, free-living primates, and other wild mammals (all of whom do not develop atherosclerosis). Randomized trial data suggest atherosclerosis progression and coronary heart disease events are minimized when LDL is lowered to <70 mg/dl. No major safety concerns have surfaced in studies that lowered LDL to this range of 50 to 70 mg/dl. The current guidelines setting the target LDL at 100 to 115 mg/dl may lead to substantial undertreatment in high-risk individuals.     

Evaluation of Low-Density Lipoprotein Particle Number Distribution in Patients With Type 2 Diabetes Mellitus With Low-Density Lipoprotein Cholesterol <50 mg/dl and Non-High-Density Lipoprotein Cholesterol <80 mg/dl

Many patients with type 2 diabetes mellitus (T2DM) have relatively normal levels of low-density lipoprotein (LDL) cholesterol yet have increased risk for cardiovascular events. Distribution of lipoprotein subclasses in patients with T2DM who have achieved very low levels of LDL cholesterol (<50 mg/dl) or non-high-density lipoprotein (HDL) cholesterol (<80 mg/dl) have not been extensively examined. The aim of this study was to assess variations in lipoprotein particle concentration in patients with diabetes with "very low" LDL cholesterol and non-HDL cholesterol levels to elucidate the drivers of residual cardiovascular risk. Data were selected from a single large clinical laboratory database. Cases were patients with T2DM diagnosis codes (International Classification of Diseases, Ninth Revision, codes 250 to 250.93). Lipoprotein particle concentrations were analyzed using nuclear magnetic resonance spectroscopy. The Friedewald equation was used to calculate LDL cholesterol. Among the 1,970 patients with T2DM, the mean age was 61 years, and approximately 51% were men. At LDL cholesterol concentrations <50 mg/dl (triglyceride <150 mg/dl and HDL cholesterol >40 mg/dl), 16% had LDL particle concentrations <500 nmol/L, 70% had concentrations of 500 to 1,000 nmol/L, and 14% had concentrations >1,001 nmol/L. At non-HDL cholesterol levels <80 mg/dl, 8% had LDL particle concentrations <500 nmol/L, 67% had concentrations of 500 to 1,000 nmol/L, and 25% had concentrations >1,001 nmol/L. In conclusion, despite attainment of LDL cholesterol <50 mg/dl or non-HDL cholesterol <80 mg/dl, patients with diabetes exhibited significant variation in LDL particle levels, with most having LDL particle concentrations >500 nmol/L, suggesting the persistence of potential residual coronary heart disease risk.     

Clinical significance of plasma lipid levels

Epidemiologic studies have established that elevated low-density lipoprotein (LDL) cholesterol values and decreased levels of high-density lipoprotein (HDL) cholesterol are risk factors for coronary artery disease (CAD). Results from clinical trials indicate that reduction in LDL cholesterol decreases the incidence of and reduces the risk of CAD. The National Cholesterol Education Program recently developed guidelines for the evaluation of plasma cholesterol in adults. Initial classification is categorized and based on the following values: less than 200 mg/dl is "desirable" blood cholesterol; from 200 through 239 mg/dl is classified as "moderate-high" blood cholesterol; and greater than or equal to 240 mg/dl is "high" blood cholesterol. Decision-making regarding therapeutic intervention is influenced by the presence of other lipoprotein risk factors, such as reduced HDL cholesterol and elevated lipoprotein (a), and nonlipid factors, including age, sex, hypertension, obesity, smoking, diabetes mellitus, and family or patient history of CAD. Persons with borderline-high blood cholesterol and established CAD or 2 other risk factors as well as those with high blood cholesterol should undergo lipoprotein analysis. LDL cholesterol is the primary lipoprotein to consider when determining treatment goals. Patients with LDL cholesterol levels greater than 160 mg/dl without CAD or 2 other risk factors and those patients with LDL cholesterol greater than 130 mg/dl with CAD or 2 other risk factors are initially managed with dietary therapy. The goal of treatment of hyperlipidemia is to reduce LDL cholesterol to less than 160 mg/dl or to less than 130 mg/dl in patients with established CAD or with 2 other risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence that triglycerides are an independent coronary heart disease risk factor

In the past, the relation between hypertriglyceridemia and coronary heart disease (CHD) has been uncertain. However, a recent multivariate analysis of 8-year follow-up data from the large-scale Prospective Cardiovascular Münster study found hypertriglyceridemia to be an independent risk factor for major coronary events after controlling for low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. Hypertriglyceridemia combined with elevated LDL cholesterol and high LDL:HDL cholesterol ratio (>5) increased the CHD event risk by approximately sixfold. Similarly, a large meta-analysis of 17 prospective trials reported hypertriglyceridemia to be an independent risk factor for cardiovascular disease. In this study, an 88 mg/dl (1.0 mmol/L) increase in plasma triglyceride levels significantly increased the relative risk of cardiovascular disease by approximately 30% in men and 75% in women; the corresponding rates were somewhat lower (14% and 37%) but still statistically significant after adjustment for HDL cholesterol level. These data and observations from patients in the Helsinki Heart Study and the Stockholm Ischemic Heart study, that the greatest coronary benefit during lipid-lowering drug therapy occurred among hypertriglyceridemic patients, argue strongly for an independent role for hypertriglyceridemia in CHD risk. In the recent Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Cholesterol Intervention Trial, the use of gemfibrozil to raise HDL cholesterol levels and lower levels of triglycerides without lowering LDL cholesterol levels reduced coronary events in men with established CHD, whereas preliminary results from the Bezafibrate Infarction Prevention Trial indicate a reduction in coronary end points in patients with elevated baseline triglyceride levels. To achieve the greatest possible reduction in CHD risk, antihyperlipidemic treatment strategies should also be aimed at reducing elevated triglycerides.     

Low-density lipoprotein cholesterol reduction: the end is more important than the means

Many epidemiologic studies and clinical trials have demonstrated the linear relation between elevated serum levels of low-density lipoprotein (LDL) cholesterol and the risk for coronary heart disease. Conversely, for each 1% reduction in LDL cholesterol in clinical trials, there is a corresponding 1% reduction in coronary heart disease risk. Although the degree of reduction is more important in affecting risk than the means used to lower LDL, statins are considered the most consistently effective means of lowering LDL. The National Cholesterol Education Program now recommends an optional goal of <70 mg/dl for patients at very high risk for coronary heart disease. In conclusion, on the basis of completed clinical trials, there is no evidence that achieving and maintaining such low levels of LDL cholesterol result in adverse effects. The most potent statins, rosuvastatin and atorvastatin, are capable of getting most patients to their LDL cholesterol goals, but combinations of statins with other drugs may be necessary for patients who require additional lipid lowering.     

Management of hyperlipidemia with statins in the older patient

Numerous randomized, double-blind, placebo-controlled studies and observational studies have demonstrated that statins decrease mortality and major cardiovascular events in older high-risk persons with hypercholesterolemia. The Heart Protection Study found that statins decreased mortality and major cardiovascular events in high-risk persons regardless of the initial level of serum lipids, age, or gender. The updated National Cholesterol Education Program (NCEP) III guidelines state that in very high-risk patients, a serum low-density lipoprotein (LDL) cholesterol level of <70 mg/dl is a reasonable clinical strategy, regardless of age. When a high-risk person has hypertriglyceridemia or low serum high-density lipoprotein cholesterol, consideration can be given to combining a fibrate or nicotinic acid with an LDL cholesterol-lowering drug. For moderately high-risk persons (2 or more risk factors and a 10-year risk for coronary heart disease of 10% to 20%), the serum LDL cholesterol should be decreased to <100 mg/dl. When LDL cholesterol-lowering drug therapy is used to treat high-risk persons or moderately high-risk persons, the serum LDL cholesterol should be decreased at least 30% to 40%.     

Treating hyperlipidemia, Part I: Whether and when in the elderly

There are elderly persons at increased risk of coronary heart disease due to elevated LDL cholesterol, lowered HDL cholesterol, or both. Risk difference data seem to indicate that the reduction in risk of coronary artery disease by lowering elevated cholesterol values is the same in the elderly as it is in younger persons. hence we recommend screening for total cholesterol in the elderly, followed by a fasting lipid profile in those with screening cholesterol values over 200 mg/dl (230 mg/dl by certain methods). Comparative LDL and HDL cholesterol values, as well as L/H ratios, are presented for assisting in assessment of results and for planning therapeutic strategy.     

To statin or to non-statin in coronary disease--considering absolute risk is the answer

The newest guidelines for treating people with coronary artery disease (CAD) suggest benefit from statin-induced LDL cholesterol lowering regardless of baseline LDL cholesterol level. These guidelines were based on recent clinical trials that showed statistically significant statin-induced relative risk reductions (RRR) in cardiovascular events. However, there are proven "non-statin" anti-atherosclerotic treatments. This analysis was designed to allow the physician to decide which patients benefit from the various anti-atherosclerotic treatments available. Analysis is presented as absolute risk reduction (ARR) because ARR takes baseline risk into account. There was a large benefit from statin therapy in stable CAD when LDL cholesterol levels were high. There were diminishing returns, despite statistically significance, with statin treatment of people with chronic CAD and lower LDL cholesterol levels. People with chronic CAD and lower LDL cholesterol levels had at least as much and possibly twice the ARR when treated with niacin or gemfibrozil as that would occur with statin treatment. For the first year after the acute coronary syndrome, risk was higher than in stable CAD, and trials showed a benefit especially with a Mediterranean diet and also with statin therapy that reduced LDL cholesterol levels to approximately 80 mg dl(-1). The Mediterranean diet was also beneficial in chronic CAD. These results suggest that both statin and non-statin therapy are important for reducing the sequelae of atherosclerosis.     

Identifying patients for aggressive cholesterol lowering: the risk curve concept

The National Cholesterol Education Program's 2004 report identified more aggressive optional low-density lipoprotein (LDL) cholesterol treatment goals of <70 mg/dl for secondary prevention patients and <100 mg/dl for moderately high risk, primary prevention patients. Although LDL cholesterol reduction is the first step in reducing cardiovascular risk, it may be difficult for clinicians to visualize the risk reduction benefit for patients from various risk interventions. The concept of a "risk curve," or the absolute risk of a patient for subsequent cardiovascular events over a range of LDL cholesterol values, is proposed. In conclusion, placing a patient on the appropriate risk curve may facilitate an individualized clinical management strategy that takes into account the patient's absolute benefit from further LDL cholesterol reduction as well as from shifting the risk curve downward through non-LDL cholesterol interventions.     

Senkung des LDL-Cholesterins

Reducing cholesterol and LDL cholesterol (LDL-C) is one of the few clearly demonstrated principles in the prevention and treatment of arteriosclerosis. LDL-C reduction over a number of years to ca. 70 mg/dl can reduce the risk of coronary events by about two thirds. Lipid lowering pharmacotherapy is the more effective the higher the individual risk of the patient is. The therapeutic decision is based on the total risk of the patient. For coronary patients after acute coronary syndrome and/or with diabetes mellitus, a reduction of LDL-C to 70 mg/dl is justified. For patients with "stable" coronary heart disease, a LDL-C level of 100 mg/dl or less should be strived for. Whether diabetes mellitus always indicates a "coronary risk equivalent" and thus justifies a reduction in LDL-C to 100 ml/dl or less, is questionable.     

Cardiovascular disease risk of type 2 diabetes mellitus and metabolic syndrome: focus on aggressive management of dyslipidemia

Type 2 diabetes mellitus and the closely related metabolic syndrome markedly increase the risk of cardiovascular disease a major contributor is the dyslipidemia. Recent studies and new national guidelines suggest these very high risk patients with cardiovascular disease achieve optional low density lipoprotein cholesterol (LDL-C) level of less than 70 mg/dl. In addition there may be no threshold to begin therapeutic lifestyle change and pharmacologic therapy to reduce LDL-C by 30-40%. Although randomized controlled trials with statins indicate that LDL reduction clearly reduces cardiovascular risk in these patients, the typical dyslipidemia of type 2 diabetes mellitus is also characterized by low high density lipoprotein cholesterol (HDL-C) levels, increased triglyceride-rich lipoproteins and small dense LDL, as well as increased postprandial lipemia. The later lipoproteins increase non-HDL-C levels. In order to address these abnormalities it may be necessary to utilize combined approaches with a fibrate or nicotinic acid, or other agents with statins to help reduce risk beyond statins. In addition, supervised, therapeutic life-style change is often underutilized therapy in patients with established coronary artery disease. This review will focus on maximizing the treatment of dyslipidemia in type 2 diabetes and the metabolic syndrome and discuss the evidence based studies and new developments in the management in these very high risk patients.     

Achieving optimal lipid goals in patients with coronary artery disease

Guidelines for lipid-lowering therapy recommend intensive low-density lipoprotein (LDL) cholesterol lowering for patients with coronary artery disease. Previous studies have found that many high-risk patients are not achieving their LDL cholesterol goals, and many patients, despite being treated with lipid-lowering therapy, also have elevated triglycerides or low levels of high-density lipoprotein (HDL) cholesterol. To evaluate lipid goals in a "real world" clinical setting, the electronic medical records of 10,040 patients with coronary artery disease from a large cardiology subspecialty practice from September 2008 to September 2009 were reviewed. Overall, 79% of patients achieved an LDL cholesterol goal of <100 mg/dl, while only 35% achieved the more aggressive goal of <70 mg/dl. Non-HDL cholesterol goals of <130 and <100 mg/dl were achieved in 79% and 44% of patients, respectively. Only 69% achieved normal triglyceride levels, and only 63% of men and 56% of women achieved normal levels of HDL cholesterol. Women and younger men were less likely to achieve their lipid goals. In conclusion, most patients with coronary artery disease achieve the minimal LDL cholesterol goal of 100 mg/dl, but few achieve the more aggressive goals of <70 mg/dl. Many high-risk patients have elevated levels of triglycerides or low levels of HDL cholesterol despite treatment. Combination lipid-lowering therapy is used infrequently in practice. There exists a significant opportunity for physicians to more aggressively treat lipids to achieve the levels recommended by clinical guidelines.     

Prevalence of low high-density lipoprotein cholesterol in patients with documented coronary heart disease or risk equivalent and controlled low-density lipoprotein cholesterol

Current guidelines identify low-density lipoprotein (LDL) cholesterol as the primary target for cardiovascular prevention but also recognize low high-density lipoprotein (HDL) cholesterol as an important secondary target. This study was conducted to determine the prevalence of low HDL cholesterol in a contemporary ambulatory high-risk population across various LDL cholesterol levels, including patients taking statins. Screening of 44,052 electronic medical records from a primary care practice identified 1,512 high-risk patients with documented coronary heart disease (CHD) or CHD risk equivalents. Low HDL cholesterol (< or =40 mg/dl in men, < or =50 mg/dl in women) was present in 66% of the 1,512 patients. Low HDL cholesterol was prevalent across all LDL cholesterol levels but most prevalent in patients with LDL cholesterol < or =70 mg/dl (79% vs 66% in those with LDL cholesterol 71 to 100 mg/dl and 64% in patients with LDL cholesterol >100 mg/dl, p <0.01). Low HDL cholesterol was equally and highly prevalent in patients taking statins (67%) and those not taking statins (64%) (p = NS). HDL cholesterol and LDL cholesterol levels correlated poorly (R(2) = 0.01), and this was unaffected by gender or statin treatment. In conclusion, in high-risk patients with CHD or CHD risk equivalents, low HDL cholesterol levels remain prevalent despite statin treatment and the achievement of aggressive LDL cholesterol goals.     

Combined effect of high low-density lipoprotein cholesterol and metabolic syndrome on subclinical coronary atherosclerosis in white men without clinical evidence of myocardial ischemia

High low-density lipoprotein (LDL) cholesterol and the presence of metabolic syndrome (MS) are established risk factors for clinical and subclinical cardiovascular disease (CVD). However, the relative contribution to CVD risk of MS and high LDL cholesterol is not well defined. Therefore, the aim was assess the relative risk for the presence of coronary artery calcification (CAC) with metabolic syndrome (MS) compared with that of moderate or high LDL cholesterol. A total of 440 consecutive asymptomatic men (mean age 46 +/- 7 years, range 29 to 65) presenting for CVD risk stratification were studied. MS was defined using National Cholesterol Education Program Adult Treatment Panel III criteria (n = 112; 24%). Moderate LDL cholesterol was defined as 130 to 159 mg/dl, and high LDL cholesterol as >/=160 mg/dl (n = 76; 17%). Overall, CAC was observed in 190 men (40%). The prevalence of CAC >0 was lowest in MS-negative men with LDL cholesterol <130 (35%) or 130 to 159 mg/dl (34%) and highest in MS-positive men with LDL cholesterol >/=160 mg/dl (80%). MS-positive men with LDL cholesterol of 130 to 159 mg/dl had CAC prevalence similar to that of MS-negative men with LDL cholesterol >/=160 mg/dl (54% vs 57%, respectively). This relation persisted with additional adjustment for age, smoking status, and cholesterol-lowering medication. In logistic regression analyses, the odds ratio for CAC >0 was highest in MS-positive men combined with high LDL cholesterol. In conclusion, these results suggest that the risk of CAC in asymptomatic men with moderate or high LDL cholesterol is magnified in persons with MS.     

Heterogeneity of low-density lipoprotein particle number in patients with type 2 diabetes mellitus and low-density lipoprotein cholesterol <100 mg/dl

Patients with type 2 diabetes mellitus have an increased risk of cardiovascular events even when treated to low-density lipoprotein (LDL) cholesterol goals. The purpose of this study was to determine how many diabetic patients with low LDL cholesterol have correspondingly low numbers of LDL particles (LDL-P) and the extent to which those achieving target levels of LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol might still harbor residual risk associated with increased LDL-P. Split-sample measurements of LDL cholesterol, non-HDL cholesterol, and nuclear magnetic resonance measured LDL-P were performed on plasma samples from 2,355 patients with type 2 diabetes seen in clinical practice and who had LDL cholesterol levels <100 mg/dl. Substantial heterogeneity of LDL-P was noted among patients with low or very low levels of LDL cholesterol. Of 1,484 patients with low LDL cholesterol (70 to 99 mg/dl), only 385 (25.9%) had low levels of LDL-P (<20th percentile of an ethnically diverse contemporary reference population), whereas 468 (31.6%) had LDL-P values >50th percentile (>1,300 nmol/L). Among the 871 patients with very low LDL cholesterol, i.e., <70 mg/dl, 349 (40.1%) had LDL-P levels >1,000 nmol/L (>20th percentile) and 91 (10.4%) had LDL-P levels >50th percentile. For patients with high triglyceride values (200 to 400 mg/dl), there was less discordance between LDL-P and non-HDL cholesterol than between LDL-P and LDL cholesterol. However, for those with triglyceride levels <200 mg/dl, LDL-P distributions were similarly wide for patients having achieved low or very low targets of LDL cholesterol or non-HDL cholesterol. In conclusion, these data demonstrate that patients with type 2 diabetes mellitus and LDL cholesterol levels <100 mg/dl are extremely heterogeneous with regard to LDL-P and, by inference, LDL-based cardiovascular risk.