Coronary Heart Disease Risk Equivalent Research Articles

Dysglycemia/Prediabetes and Cardiovascular Risk Factors

Obesity and diabetes are becoming a pandemic in developing and industrialized countries. Based on the current criteria, 24.1 million Americans have diabetes, and another 57 million have prediabetes. The term prediabetes refers to people who have impaired fasting glucose (100-125 mg/dL), impaired glucose tolerance (2-hour postglucose load of 140-199 mg/dL), or both. Many persons with prediabetes already have microvascular disease consequences (eg, blindness, amputations, kidney failure) similar to those seen in patients with a diagnosis of diabetes. However, it is not established whether prediabetes should be considered a coronary heart disease risk equivalent. Whether dysglycemia is a surrogate for a more complex metabolic condition and/or directly increases cardiovascular disease (CVD) risk remains unclear. However, many studies have shown that hyperglycemia, through various mechanisms, can lead to premature atherosclerosis. In this regard, several diabetes prevention trials have shown that strategies that reduce the rate of conversion to diabetes can also modify CVD risk factors.

Coronary Artery Calcium: A Clue to the Enigma of Tight Glycemic Control and Cardiovascular Disease?

Among individuals with diabetes, dyslipidemia, hypertension, and other processes contribute to the development of atherosclerosis, which underlies most cardiovascular disease (CVD), the leading cause of mortality in diabetes (1). However, people with both type 1 and type 2 diabetes are likely more susceptible to CVD due to hyperglycemia, abnormal fatty acid metabolism, and insulin resistance, which have adverse effects on the vascular endothelium (2). The impaired endothelium promotes vasoconstriction, inflammation, and thrombosis, which in turn promote the formation of atherosclerotic plaques (2). Occlusion of coronary arteries by plaque rupture and thrombosis underlies coronary heart disease (CHD) (3). Calcium is deposited in early atherosclerosis lesions; in advanced plaques, the calcification is extensive and can be detected by chest computed tomography (CT) (4). The amount of coronary artery calcium (CAC) present is correlated strongly with the overall burden of atherosclerosis in the coronary arteries (4). There is increasing consensus that CAC score is predictive of future CHD and CVD events and may improve prediction beyond that of the Framingham Risk Score (5). How to best prevent CVD among individuals with diabetes remains the focus of much research. Since the publication of the National Cholesterol Education Program's most recent guideline, it has been common to classify all adults with diabetes as CHD risk equivalents (i.e., Framingham Risk Score >2% per year) eligible for aggressive risk factor modification (6). There is evidence of benefit for lipid-lowering, antihypertensive, and antiplatelet therapies (7). Despite data supporting a direct relationship between glucose control and CVD (8), early randomized controlled trials (RCTs) did not demonstrate that glucose control prevented …

Dyslipidemia as a Risk Factor for Ischemic Stroke

Ischemic stroke is a major cause of morbidity and mortality. Whereas dyslipidemia is a major risk factor for coronary heart disease (CHD), its role in the pathogenesis of ischemic stroke is less clear. Epidemiological studies have provided conflicting findings regarding the association of dyslipidemia with ischemic stroke. Overall, elevated LDL-C levels appear to increase the risk of ischemic stroke. Low HDL-C levels also appear to be associated with a greater risk whereas the importance of high triglyceride levels is less clear. The discordant results of observational studies might result from the heterogeneity of stroke, since dyslipidemia is less likely to play a major role in the pathogenesis of some ischemic stroke subtypes (e.g. lacunar and cardioembolic strokes) and elevated LDL-C levels might increase the risk of hemorrhagic stroke. In clinical trials, statins consistently reduced the risk of ischemic stroke in patients with or without CHD whereas the data on the effects of other lipid modifying drugs on stroke risk are limited. In patients with a previous stroke, statins reduce the risk of both ischemic stroke and other vascular events but also increase the risk of hemorrhagic stroke. Accordingly, current guidelines recommend the same lipid targets for the primary and secondary prevention of both stroke and CHD. In addition, stroke and transient ischemic attacks of carotid origin are considered CHD risk equivalents. Nevertheless, more trials are required to identify which patients with stroke but without CHD will benefit more from statin treatment.

Design of the DEFINE trial: Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib

Residual cardiovascular (CV) risk often remains high despite statin therapy to lower low-density lipoprotein cholesterol (LDL-C). New therapies to raise high-density lipoprotein cholesterol (HDL-C) are currently being investigated. Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that raises HDL-C and reduces LDL-C when administered alone or with a statin. Adverse effects on blood pressure, electrolytes, and aldosterone levels, seen with another drug in this class, have not been noted in studies of anacetrapib to date. Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib (DEFINE) is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease (CHD) or CHD risk equivalents (clinical trials.gov NCT00685776). Eligible patients at National Cholesterol Education Program-Adult Treatment Panel III LDL-C treatment goal on a statin, with or without other lipid-modifying medications, are treated with anacetrapib, 100 mg, or placebo for 18 months, followed by a 3-month, poststudy follow-up. The primary end points are percent change from baseline in LDL-C and the safety and tolerability of anacetrapib. Comprehensive preplanned interim safety analyses will be performed at the 6- and 12-month time points to examine treatment effects on key safety end points, including blood pressure and electrolytes. A preplanned Bayesian analysis will be performed to interpret the CV event distribution, given the limited number of events expected in this study. A total of 2,757 patients were screened at 153 centers in 20 countries, and 1,623 patients were randomized into the trial. Lipid results, clinical CV events, and safety outcomes from this trial are anticipated in 2010.

Coronary Heart Disease and Dyslipidemia: A Cross‐Sectional Evaluation of Prevalence, Current Treatment, and Clinical Control in a Large Cohort of Spanish High‐Risk Patients: The PRINCEPS Study

The authors assessed a large cohort of patients with coronary heart disease (CHD) or at high risk for developing CHD in terms of lipid profile, lipid-lowering treatment, and attainment of National Cholesterol Education Program (NCEP) target low-density lipoprotein cholesterol (LDL-C) levels. The investigation was a cross-sectional study involving Spanish outpatients treated in primary or secondary care facilities. From a total of 26,598 attending patients, 12,128 with CHD or CHD risk equivalents were recruited by 1875 physicians; 49% had CHD and 69% had multiple risk factors. Only 25% of patients attained LDL-C values <100 mg/dL, 76.6% patients received lipid-lowering therapy (statins in 95.4% of cases), and 54% of physicians considered that a treatment change was required (the most frequent choice was the addition of ezetimibe to current statin therapy). In this large cohort of high-risk coronary patients, only 25% attained a target LDL-C of <100 mg/dL. These results highlight a need for improved patient care and physician awareness/training.

A Review of Lipid Management in Primary and Secondary Prevention

Lipid management in primary and secondary prevention reduces cardiovascular morbidity and mortality. Lowering of low-density lipoprotein cholesterol (LDL-C) levels with statins remains the primary goal of therapy. For secondary prevention patients, those with coronary heart disease (CHD) or CHD risk equivalents, intensive LDL-C lowering is recommended, although the precise target value is still debated. For primary prevention, reduction in LDL-C levels is based on patient risk for CHD. In clinical outcome trials to date, statins benefit those who are at moderate to high risk and appear to have less clinical benefit for those at low risk. Yet despite aggressive LDL-C management with statins, there remains a residual risk for CHD events in high-risk patients. Secondary targets have been proposed to decrease this risk, including non-high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and apolipoprotein B, as well as other emerging targets, including LDL particle number and lipoprotein(a). In many high-risk patients, statin monotherapy is unlikely to achieve goals, and combination therapy with other agents is a safe, effective, and optimal therapeutic approach.

Flushing ASsessment Tool (FAST©)

A common adverse effect of niacin therapy is flushing, manifested by cutaneous warmth, redness, itching and/or tingling. The Flushing ASsessment Tool (FAST) was developed to assess flushing symptoms and their impact on patients receiving niacin therapy. This study evaluated the reliability, validity and responsiveness of the FAST. The minimal important difference (MID) of the FAST was also examined. This was a prospective, randomized, double-blind, placebo-controlled, parallel-group 8-week study conducted to evaluate the psychometric characteristics of the FAST. The instrument is administered daily using an electronic patient diary. The study was conducted at 41 clinical sites in the US. 276 patients with dyslipidaemia were randomized to treatment and were at least 18 years of age, with fasting laboratory values of low-density lipoprotein cholesterol (LDL-C) <250 mg/dL and one of the following: high-density lipoprotein cholesterol (HDL-C) <40 mg/dL for males or <50 mg/dL for females; or triglycerides (TG) > or = 150 and < or = 400 mg/dL; or LDL-C > or = 70 mg/dL for patients with a history of coronary heart disease (CHD) or CHD risk equivalents, or > or = 100 mg/dL for subjects with two risk factors, or > or = 160 mg/dL for subjects with 0-1 risk factors. Patients were randomized (1 : 1 : 1) to receive niacin extended-release (NER) 500 mg/day in week 1, 1000 mg/day in week 2 and 2000 mg/day in weeks 3-6/aspirin (acetylsalicylic acid [ASA]), NER/ASA placebo, or NER placebo/ASA placebo. FAST test-retest reliability in stable patients during the first 2 weeks was demonstrated for overall flushing severity using patient and physician overall treatment effect (OTE) ratings (intraclass correlation coefficients of >0.7 for mean overall and individual flushing severity scores). Over the 6-week treatment period, FAST scores demonstrated significant correlations with individual symptoms, impact on daily activities and sleep, and dissatisfaction related to flushing (p < 0.01). Changes in FAST scores were associated with treatment satisfaction (p < 0.01) and patient- and physician-rated OTE (p < 0.01). Using patient-rated OTE, the mean maximum flushing severity scores improved 1.85 points in responders and only 0.18 points in non-responders (p < 0.001); responders were defined by improved patient- or physician-rated OTE. Among patients with flushing, mean maximum overall flushing scores differed between patients who subsequently discontinued due to flushing (7.9 points) and those who did not discontinue (4.7 points; p < 0.001). The probable range in this study for a detectable change in flushing symptoms (MID) was 0.29-0.38 points for mean flushing severity and 0.66-0.86 points for maximum flushing severity. The FAST exhibited test-retest reliability, good evidence of construct validity, and, overall, flushing severity was responsive to change over time. The FAST is a reliable and valid instrument for assessing the impact of niacin-induced flushing in patients with dyslipidaemia.

Abstract 3704: Prevalence of Lipid Disorders and Treatment Patterns in Overall and High Risk U.S. Adults with Dyslipidemia in 2003–2004

Background: Recent data on the extent of lipid disorders and treatments used among U.S. adults with dyslipidemia are limited; particularly among those with high coronary heart disease (CHD) risk. We therefore examined the prevalence of lipid disorders and utilization of lipid modifying therapies (LMT) to determine any gaps in therapy. Methods: We identified 1,111 U.S. adults aged ≥20 years (mean age 56 years, 45% female; representing 126 million US adults) with dyslipidemia (defined as elevated LDL-C as per National Cholesterol Education Program guidelines, or being on LMT) from the National Health and Nutrition Examination Survey 2003–2004. Of these, 609 (representing 19.4 million) adults with dyslipidemia were identified as high risk (i.e. CHD, diabetes or other CHD risk equivalents). LMT included statins, fibrates, niacin, cholesterol absorption inhibitors, bile acid sequestrants, as well as combination therapies. Lipid disorders were defined according to deviation from recommended levels for LDL-C (target level defined according to updated NCEP guidelines by risk group), HDL-C (≥40mg/dL for men and ≥50mg/dL for women) and triglycerides (TG) (&lt;200 mg/dL). Results: Of the total population (n=1,111) with dyslipidemia, 85% remained uncontrolled for LDL-C, HDL-C, and or TG; 36% had ≥2 lipid disorders, while 42% had HDL-C and/or TG disorders with or without elevated LDL-C. Among high risk subjects, 88% remained uncontrolled on ≥1 of these lipid parameters; 36% had ≥2 lipid disorders simultaneously while 43% had HDL-C and/or TG disorders irrespective of LDL-C levels. However, only 34% (39% among high risk) were on LMT. Of those on treatment, monotherapy with statins was most common (~80%), followed by statin combination therapy (8 –10% depending on risk status). Conclusions: Our cross-sectional assessment of US adults suggests that despite high prevalence of lipid disorders (up to 85%), LMT is utilized by &lt;40% of subjects. Furthermore, there is a large disconnect between high prevalence of HDL and/or TG disorders, with or without elevated LDL-C, and utilization of therapies targeting these lipids (&lt;10% of therapy utilized was non-statins), a particular concern among high risk patients.

Stroke is a coronary heart disease risk equivalent: implications for future clinical trials in secondary stroke prevention

With an estimated 1 million cases per year in Europe, 1.2 million in North America, and 10 millions in the rest of the world, the burden of stroke is enormous. Stroke includes brain haemorrhage, transient ischaemic attacks (TIAs), and cerebral (brain) infarction (each of these causes accounting for approximately 15, 15, and 70% of cases, respectively).1,2 Overall, a quarter of all stroke patients has a history of a symptomatic coronary event.3 These patients are prone to recurrent coronary heart disease (CHD) events. In the PROGRESS trial, in the subset of patients with recent stroke and a history of CHD, the risk of a new CHD event was as high as the risk of a new stroke,4 but in the remainder of stroke patients without overt CHD, the risk of CHD events or pre-symptomatic CHD has not been well evaluated. The main modifiable risk factors in stroke patients include hypertension, diabetes, atrial fibrillation, cigarette smoking, hypercholesterolaemia, obesity, physical inactivity, and alcohol consumption.5 These factors increase the risk for other vascular disease, including CHD, except perhaps atrial fibrillation. As a consequence, stroke is usually part of a global disease. The REACH registry has shown that 40% of 19 000 stroke patients have one or two other locations of vascular disease such as coronary artery disease (CAD) and peripheral arterial disease.6 Patients with stroke are at high risk of having another major vascular event such as stroke, myocardial infarction (MI), or vascular death. Observational studies and clinical trials have shown that during the 2 years following a stroke, the next most common event …

211: Low-Density Lipoprotein Cholesterol Lowering by High-Efficacy Statins: Are Older Women at an Advantage?

Synopsis: In the PROSPER trial, high-risk, older women had higher low-density lipoprotein cholesterol (LDL-C) levels than men at baseline (154 vs. 139 mg/dL), resulting in higher on-treatment LDL-C despite marginally greater response to statin treatment. Purpose: We assessed the more effective statins by sex and age subgroups in a trial of high-risk patients. Methods: In the SOLAR trial (4522US/0003), 1632 patients with LDL-C 130 –250 mg/dL were randomized to rosuvastatin (RSV) 10 mg, atorvastatin (ATV) 10 mg, or simvastatin (SMV) 20 mg for 6 weeks. LDL-C reductions from baseline were compared between treatment groups by ANCOVA and LDL-C goal attainment by logistic regression. Results: Mean age was 62y; the cohort was 58% male and 91% had CHD or CHD risk-equivalents. Mean baseline LDL-C for women and men 65y was 168 and 166 mg/dL, respectively. For women and men 65y, mean baseline LDL-C was 176 and 164 mg/dL. In all 4 subgroups, % LDL-C reduction and % of patients achieving LDL 100 mg/dL were greater for RSV than for ATV or SMV (Table). Older women achieved greater LDL-C reduction than younger women, but goal attainment was not more frequent, apparently due to higher baseline LDL-C levels. Of older women and men, 67% and 73% respectively achieved LDLC 100 mg/dL with RSV 10 mg. Conclusions: Baseline LDL-C was elevated in older women, but increased statin response produced final LDL-C values similar to those of younger women. Goal attainment in older patients suggested a gender difference that should be confirmed in further studies.

213: Short-Term Treatment with Ezetimibe Does Not Reduce Plasminogen Activator Inhibitor-1 Compared to Simvastatin

150 mg/dL). Treatment groups were compared by ANCOVA. Results: Mean age was 62 years; the cohort was 58% male, and 91% had CHD or CHD risk-equivalents. The HDL-C increase observed with all 3 statins was greater among patients with low HDL-C or high TG or both, than among other patients (Table). Similarly, TG reduction with all 3 statins was greater among patients with low HDL-C or high TG or both, than among other patients. Percent increase in HDL-C and percent reduction in TG were nominally greater with RSV than with the other statins. LDL-C reduction did not differ between HDL-C or TG subgroups. Conclusions: Statins, particularly RSV, are more effective in raising HDL-C and lowering TG in patients who most need these benefits, that is, those with low HDL-C or high TG or both.

Not all diabetics are created equal (in cardiovascular risk)

Current guidelines continue to recommend all persons with diabetes be considered at high risk and treated accordingly. For example, National Cholesterol Education Panel Guidelines state ‘Persons with type 2 diabetes should be managed as a coronary heart disease (CHD) risk equivalent. Treatment for low density lipoprotein (LDL) cholesterol should follow Adult Treatment Panel III recommendations for persons with established CHD’.1 This remains an important tenet, as up to 80% of persons with diabetes will suffer a cardiovascular event. This has led some to conclude that further risk stratification in persons with diabetes is neither warranted nor useful. However, persons with diabetes are not all at equal risk. The data from PREDICT,2 as well as previous coronary artery calcium (CAC) studies, demonstrate that persons with diabetes will have widely varied cardiovascular risk. While many persons with diabetes do have increased cardiovascular risk compared with the general population, there is a defined subset who have a very low cardiovascular risk and an equally large subset who are at extremely high risk. These groups cannot be discerned on the basis of HbA1c levels, duration of diabetes, age, gender or cardiovascular risk factors. Clearly, coronary calcium scanning (CCS) is not only becoming widely accepted in intermediate risk patients, such as those with several cardiovascular risk … *Corresponding author. Tel: (310) 222 4107, Fax: (310) 787 0448, E-mail: mbudoff{at}labiomed.org

Cholesterol Goal Attainment in Patients with Coronary Heart Disease and Elevated Coronary Risk: Results of the Hong Kong Hospital Audit Study

Objective We sought to determine 1) long-term lipid-lowering treatment patterns; 2) cholesterol goal attainment rates and possible determinants of goal achievement; and 3) effects of cholesterol goal attainment on coronary events in hospitalized Hong Kong patients. Methods In this retrospective cohort analysis, records of two public Hong Kong hospitals were reviewed for 196 adults (69% with coronary heart disease (CHD) or CHD-risk equivalent) who received at least one lipid-lowering therapy during hospitalization. Low-density lipoprotein cholesterol (LDL-C) targets were <2.6 mmol/l (<100 mg/dL) for patients with CHD or CHD risk equivalents and <3.37 mmol/l (<130 mg/dL) for those without. Results Most participants were initiated on regimens of low to midequipotency doses and never had their regimens adjusted to higher potency. Approximately 44% of patients not at LDL-C at baseline failed to achieve goal during a median follow-up of 1.9 years. Patients with higher coronary risk and/or LDL-C levels at baseline were less likely than their lower-risk counterparts to achieve goal; for each 1-mmol/l (38.7-mg/dL) increase in LDL-C at baseline, the likelihood of attaining goal declined by 64%. Patients achieving cholesterol goal had significantly longer cardiovascular event-free times. Conclusions A total of 44% of Hong Kong patients not at LDL-C goals at baseline did not achieve them over 1.9 years. More effective and well-tolerated therapies, including adjunctive regimens (e.g., ezetimibe-statin, niacin-statin), may be necessary to enhance LDL-C goal achievement and increase event-free time.

Contemporary risk factor control and walking dysfunction in individuals with peripheral arterial disease: NHANES 1999–2004

Background Lower extremity peripheral arterial disease (PAD) is a coronary heart disease (CHD) risk equivalent. Selected studies have demonstrated less intense risk factor management and diminished mobility in individuals with PAD as compared to individuals with clinical recognized CHD. However, comparable data have not been reported from a nationally representative population. Objectives To assess the prevalence, treatment, and control of cardiovascular risk factors among individuals with PAD as defined by an ankle-brachial index (ABI) <0.90 (but without recognized CHD) as compared with individuals with recognized CHD (but without PAD). A second objective was to evaluate the diagnostic accuracy of measures of walking dysfunction to identify individuals with PAD. Design, setting, and participants We analyzed data from 7571 participants aged 40 or older who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2004, a nationally representative cross-sectional survey of the U.S. population. Results The prevalence of PAD without CHD was 4.1% (95% CI 3.6–4.5) compared to 7.9% (7.1, 8.9) for CHD (without PAD). Hypertension prevalence was similar, but treatment and control rates were lower among individuals with PAD compared to CHD (treatment: 69% vs. 84%, p < 0.001; control: 50% vs. 63%, p = 0.01). Treatment of hypercholesterolemia was lower among individuals with PAD (54% vs. 79%, p < 0.001) but control was similar (83% vs. 85%, p = 0.78). Diabetes awareness, treatment, and control did not differ between the two groups. Walking mobility limitations were specific, but insensitive, for the identification of individuals with PAD. Conclusion PAD in the absence of clinically recognized CHD is under-treated and poorly controlled in the general U.S. population. Leg symptoms are not adequate to identify individuals with PAD, who are at high risk of ischemic events.

Primary Prevention of Cardiovascular Disease in People With Dysglycemia

Cardiovascular disease accounts for a great majority of deaths in patients with type 2 diabetes. According to the World Health Organization, the prevalence of cardiovascular disease in diabetic patients ranges from 26 to 36%. Fatality rate after myocardial infarction is greater in diabetic patients, and overall prognosis after coronary heart disease is worse. Based on these observations, it has been proposed that diabetes should be considered as a coronary heart disease risk equivalent. If that is the case, prevention of diabetes and early intervention should be pursued. This view is supported by the notion that cardiovascular risk is already increased in people with impaired glucose tolerance. Moreover, higher-than-optimum blood glucose is a major cause of cardiovascular mortality in most world regions of the world. Whether dysglycemia is a marker for a more complex metabolic condition or may directly contribute to excess cardiovascular risk is still a matter of debate. However, experimental work has shown how increased glucose level can trigger multiple mechanisms of susceptibility to atherosclerosis, and diabetes prevention trials have indicated that along with reduction of the rate of conversion toward diabetes, significant improvement in cardiovascular risk factors occurs. Moreover, in the STOP-NIDDM trial, targeting postprandial glucose was associated with reduction in new cases of hypertension, myocardial infarction, and any cardiovascular events. In conclusion, dysglycemia should be included in the list of established cardiovascular risk factors and early treatment introduced in the attempt to improve cardiovascular morbidity and mortality.

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.

Efficacy and safety of extended-release fluvastatin in Turkish patients with hypercholesterol­aemia: TULiPS (Turkish Lipid Study)

ABSTRACTObjective: The efficacy and safety of extended-release fluvastatin (fluvastatin XL), 80 mg once daily, was assessed in Turkish patients with primary hypercholesterolaemia (low-density lipoprotein cholesterol (LDL‑C) 3.37–5.70 mmol/l and triglyceride (TG) < 4.52 mmol/l).Research design: in this open-label, prospective, multi-centre study, 154 patients were given fluvastatin XL 80 mg once daily and lipid levels were assessed after 2 and 12 weeks.Results: Fluvastatin XL 80 mg once daily significantly reduced LDL‑C levels by 38.8 and 38.1% at weeks 2 (n = 140) and 12 (n = 116), respectively ( p < 0.001 vs. baseline). Treatment with fluvastatin XL for 2 and 12 weeks significantly reduced total cholesterol levels by 30.2 and 27.4%, respectively ( p < 0.001 vs. baseline) and reduced TG levels by 14.9 and 7.5%, respectively ( p < 0.001 vs. baseline). Following stratification by risk factors for coronary heart disease (CHD) according to the National Cholesterol Education Program Adult Treatment Panel iii guidelines, 87.3% of patients with ≥ 2 risk factors, and 67.4% of patients with existing CHD or CHD risk equivalents achieved target LDL‑C levels (< 3.37 mmol/l and < 2.59 mmol/l, respectively) with fluvastatin XL. Fluvastatin XL reduced high-density lipoprotein cholesterol by 8.9 and 4.7% at weeks 2 and 12 weeks, respectively. fluvastatin XL 80 mg once daily was generally well-tolerated.Conclusions: This open-label study indicates fluvastatin XL 80 mg once daily is an effective and well-tolerated lipid-lowering therapy for the reduction of CHD risk in Turkish patients.

Use of maximum-dose simvastatin or atorvastatin in an ethnically diverse population

The use of maximum-dose simvastatin or atorvastatin in an ethnically diverse population was studied. This retrospective analysis was conducted at a publicly funded teaching institution whose predominant patient population consists of Hispanics and Asians. A computer-generated report was used to identify outpatients who received a prescription for maximum-dose simvastatin or atorvastatin between January 1, 2002, and January 1, 2004. Data evaluated included demographic information; metabolic syndrome elements; coronary heart disease (CHD) risk equivalents; clinical characteristics placing patients at very high risk of having a CHD event; 10-year Framingham risk score; documentation of hepatotoxicity, myalgia, myositis, or rhabdomyolysis during maximum-dose therapy; concomitant medication during maximumdose therapy; relevant laboratory test values; and physician response to biochemical abnormalities or adverse events associated with maximum-dose therapy. Of the 232 outpatients identified, 173 were eligible for study inclusion. A total of 135 patients were classified as having a high or very-high risk of developing CHD (68 and 67, respectively). The success rates for low-density-lipoprotein (LDL) cholesterol goal attainment by very-high-risk patients and high-risk patients were 19.4% and 44.1%, respectively. Thirteen patients developed myalgia. Alanine transaminase levels were monitored for 38.8% of the study patients. Approximately 9% of patients were prescribed one interacting medication while on maximum-dose simvastatin or atorvastatin. The most commonly prescribed interacting drug was gemfibrozil. Despite the use of maximum-dose simvastatin or atorvastatin, target LDL cholesterol goals were not achieved and statin use was not adequately monitored in an ethnically diverse population with a high or very high risk of developing CHD.

Risk of cardiovascular events in patients at optimal values for combined lipid parameters

ABSTRACTBackground: Current prevention guidelines support efforts to achieve optimal high-density lipoprotein (HDL‑C) and triglyceride (TG) values, in addition to low-density lipoprotein (LDL‑C) in order to reduce cardiovascular (CV) events. The study objective was to evaluate the risk of CV events in patients attaining versus not attaining combined (LDL‑C, HDL‑C, and TG) optimal lipid values.Methods/results: This retrospective cohort analysis was conducted using a 1.1 million member managed care database. Eligible patients had a full lipid panel between 10/1/99 and 9/30/00, were naive to lipid therapy, and had health plan eligibility 12 months pre- and post-index (baseline) lipid laboratory value. Optimal lipid values (LDL‑C, HDL‑C, and TG) were established using the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) guidelines, and patients were placed into one of four groups: none, one, two, or three lipid components non-optimal at baseline. The presence of cardiovascular risk, disease, and events were determined by selected International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9 CM) and Current Procedural Terminology (CPT codes). The definition of a CV event included: diagnosis of ischemic heart disease, peripheral arterial disease, stroke/TIA, or revascularization procedure. Odds ratios (OR) for a CV event associated with attainment of each optimal lipid fraction were determined by multivariate logistic regression. The study cohort included 30 348 patients, with a mean follow-up of 27 ± 8 months. Mean age was 66 ± 12 years; 16 549 (54%) were male; and 17 289 (57%) patients had coronary heart disease (CHD) or CHD risk equivalent. There were 5955 CV events that occurred in 4059 (13%) study patients. The presence of a single non-optimal lipid value slightly increased CV event risk [OR: 1.06; 95% CI: 0.95–1.18], whereas two or all three non-optimal lipid values significantly increased the risk of a CV event [OR: 1.22; 95% CI: 1.08–1.37; and 1.45; 95% CI: 1.24–1.68, respectively].Limitations: As with all large observational databases there are potential limitations including: patient selection bias (e.g., more interventions in patients with greater illness, lack of mortality data, and frequency of lipid monitoring), unknown confounding variables, and potential coding errors.Conclusion: Not attaining optimal combined lipid values, independently and significantly, increased the risk of CV events in this large at-risk population with approximately 68 283 patient-years of follow-up. The combination of non-attainment of optimal LDL‑C with non-attainment of optimal HDL‑C or TG values, or both, increased the adjusted risk of CV events by 22–45%. Thus, therapeutic strategies should focus on assessment and management of multiple lipid abnormalities, and not on single lipid risk factor modification.

Achievement of optimal combined lipid values in a managed care setting: Is a new treatment paradigm needed?

Background: Published guidelines suggest the management of high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) values after the low-density lipoprotein cholesterol (LDL-C) goal is achieved. Objective: This study evaluated the attainment of optimal combined lipid values (LDL-C, HDL-C, and TGs) and associated therapy over time. Methods: This retrospective cohort analysis was conducted among managed-care patients who had a baseline lipid panel taken between October 1, 1999, and September 30, 2000; were naive to lipid therapy; and had plan eligibility for at least 12 months before and 12 to 36 months after the baseline lipid values. Patients were categorized as elevated-risk primary prevention (ERP) or as coronary heart disease (CHD) and CHD risk equivalents (CHD-RE). The attainment of optimal combined lipid values was assessed at baseline and quarterly thereafter. Associations between lipid values and the use of lipid-altering therapy were assessed using multivariate logistic regression. Results: A total of 30,348 patients were monitored for a mean (SD) duration of 27 (8) months. Mean (SD) age was 66 (12) years and 55% (16,549/30,348) were men; 43% (13,059/30,348) were categorized as ERP and 57% (17,289/30,348) as CHD-RE. Combined lipid values were optimal in 14% (4167/30,348),18% (5508/30,348), and 22% (2936/13,100) of patients at baseline, 12 months, and 36 months, respectively. After 36 months, 78% (10,164/13,100) of patients did not attain optimal combined lipid values. Lipid therapy, primarily statin monotherapy (87% [7992/ 92251), was prescribed in 30% (9225/30,348) of patients. After 36 months, 34% (4492/13,100) of patients had isolated elevated LDL-C and 20% (2588/13,100) had nonoptimal HDL-C and/or TGs. Lipid therapy was associated with the attainment of optimal combined values for LDL-C and TGs (both, P < 0.05), but not for HDL-C. Because the study was retrospective, causality cannot be determined. Conclusions: Based on the results of this study, use of combination lipid therapy and targeted therapy aimed at the specific lipid abnormalities may increase the attainment of optimal lipid parameters.