National Cholesterol Education Program Risk Research Articles

Impact of Co-Morbid Mental Illness on the Diagnosis and Management of Patients Hospitalized for Medical Conditions in a General Hospital

Comorbidities including hyperglycemia, diabetes, and hypertension are frequently observed in psychiatric patients. Nevertheless, this population has higher rates of morbidity and mortality from medical illnesses compared to non-psychiatric patients. The present study evaluated the diagnosis and management of general medical hospitalized patients with and without mental illness. The study group consisted of 200 hospitalized subjects including 100 subjects who met the DSM-IV criteria for schizophrenia or bipolar disorder and 100 age-matched controls. All patients were evaluated for a comorbid condition, concomitant medication, biochemical parameters. Comorbid conditions were defined using the National Cholesterol Education Program risk factors categories: diabetes (fasting plasma glucose level > or = 126 mg/dl and/or pharmacological treatment); hypertension (systolic blood pressure > or =140 mm Hg and/or diastolic BP > or = 90 mm Hg and/or pharmacological treatment); dyslipidemia (hypertriglyceridemia (> or = 150 mg/dl); and/or pharmacological treatment and/or low HDL cholesterol level (< 40 mg/dl in men and < 50 mg/dl in women). The two groups were similar in terms of age, sex, mean blood pressure, glucose, and lipids. Patients with a history of psychiatric illness were less frequently diagnosed with medical conditions such as hypertension, dyslipidemia, and diabetes compared to the non-psychiatric population, though according NCEP criteria, these conditions did not significantly differ between the two groups. Significantly fewer psychiatric than non-psychiatric patients received aspirin, statins, anti-hypertensive and anti-diabetic medications. Although more obesity was diagnosed in psychiatric patients, significantly fewer diet consults were performed during hospitalization. While significantly more smokers and more pulmonary hospitalizations were observed in the psychiatric group, fewer subjects in this group received instruction for smoking cessation compared to the non-psychiatric population. Comorbid medical conditions such as diabetes, hypertension, dyslipidemia, and obesity are under-diagnosed and under-treated in hospitalized psychiatric patients compared with the non-psychiatric population. Patients with mental illness have significantly less preventive intervention during hospitalization.

Subclinical Coronary Artery Disease as Detected by Coronary Computed Tomography Angiography in an Asymptomatic Population

Background and ObjectivesPrimary prevention of coronary artery disease (CAD) has become a public health issue, according to increasing awareness of the substantial risks posed by asymptomatic atherosclerosis. The aims of this study were to determine the prevalence and characteristics of subclinical CAD using coronary computed tomography angiography (CCTA), and to evaluate the role of this advanced technology in identifying subclinical CAD in asymptomatic Korean individuals, compared with conventional risk stratification.Subjects and MethodsWe enrolled 4,320 consecutive asymptomatic individuals (61% males, aged 50±9 years), who underwent 64-slice CCTA during a routine health check.ResultsCoronary artery plaques were present in 1,053 (24%) individuals. Significant stenosis (diameter stenosis ≥50%) was identified in 139 (3%) subjects, and most of the significant lesions (87%) were located in the left anterior descending artery. CCTA revealed noncalcified plaques in 5% of subjects with a coronary calcium score of zero (n=801). Although 25% (n=10) of those with noncalcified plaque had significant stenosis, most of them (90%) were classified into low- or moderate-risk groups according to National Cholesterol Education Program risk stratification guidelines. In a young population (age ≤55 years for males, ≤65 years for females), 30% of subjects with significant stenosis were classified into a low-risk group and 60% had low (0 to 100) calcium scores.ConclusionSubclinical CAD in asymptomatic individuals cannot be ignored for its considerable prevalence, CCTA may be helpful in identifying at-risk subclinical CAD in a noninvasive manner, especially in the young and traditionally low-risk population.

Carotid Intima-Media Thickness: Knowledge and Application to Everyday Practice

Heart disease is the primary cause of death in the United States. Fortunately, intervention measures can reduce the risk of cardiovascular disease (CVD) after a patient has been accurately assessed. Atherosclerotic disease, one of the driving forces behind CVD, is not always detected by traditional risk assessment. Carotid intima-media thickness (CIMT), as measured by B-mode ultrasound, is a surrogate marker for atherosclerosis and can be used to detect an accelerated disease process and subclinical disease. Advantages of CIMT are that it is noninvasive, relatively inexpensive, and can be repeatedly performed with no adverse effects on the patient. Carotid intima-media thickness is associated with CVD and is an independent predictor of stroke and myocardial infarction. Therefore, CIMT is valuable for clarifying CVD risk, particularly for patients with intermediate risk by conventional risk assessment. Screening for subclinical disease even in low-risk patients may have benefit, especially for those with a family history of premature CVD or those with any of the National Cholesterol Education Program risk factors. The detection of subclinical atherosclerosis allows the physician to implement prevention efforts prior to a devastating CVD event and to investigate possible reasons for increased arterial thickening, such as an occult underlying insulin-resistant condition or residual lipid risk markers. Treatment with several types of drugs has been demonstrated to halt the progression or even reduce CIMT. Carotid intima-media thickness is currently limited by the lack of standardized protocols that may affect reproducibility from measure to measure. Efforts to draft a standardized protocol are underway by the Society of Atherosclerosis Imaging and Prevention that will address this issue. Carotid intima-media thickness provides a valuable tool for physicians to clarify the CVD risk of their patients. Practical implications of CIMT for everyday clinical practice are addressed.

Low-Density Lipoprotein Cholesterol Reduction and Goal Achievement With Ezetimibe/Simvastatin Versus Atorvastatin or Rosuvastatin in Patients With Diabetes, Metabolic Syndrome, or Neither Disease, Stratified by National Cholesterol Education Program Risk Category

Patients with diabetes mellitus (DM) and metabolic syndrome are at increased risk of coronary heart disease (CHD). Studies have shown differential statin efficacy on low-density lipid cholesterol (LDL-C) by CHD risk strata. The aim of this study was to evaluate the consistency of effect with ezetimibe/simvastatin (E/S) combination therapy, atorvastatin, or rosuvastatin in patients with DM, metabolic syndrome, or neither condition (No DM/metabolic syndrome), stratified by the National Cholesterol Education Panel Adult Treatment Panel III (NCEP ATP III) CHD risk group. Post hoc analyses of 2 multicenter, double-blind, randomized, 6-week studies comparing E/S 10/10, 10/20, 10/40, or 10/80 mg with either atorvastatin 10, 20, 40, or 80 mg, or rosuvastatin 10, 20, or 40 mg. Treatments were compared by pooling across all doses for LDL-C reduction and NCEP LDL-C goal attainment in patients with DM, metabolic syndrome without DM, or No DM/metabolic syndrome across NCEP CHD risk strata. NCEP LDL-C goal attainment was lowest in the high-risk group with atherosclerotic vascular disease (12-64%) and greatest in the moderate and low-risk groups (84-100%). In contrast, LDL-C reduction was generally similar irrespective of disease or risk subgroup. All treatments were generally well tolerated, with overall similar safety regardless of disease and risk level. In these studies, CHD risk strata were inversely related to the likelihood of attaining NCEP LDL-C goals, but did not appear to affect the percentage LDL-C change from baseline. This demonstrates the need for especially aggressive cholesterol lowering necessary to reach the lower LDL-C goal for high-risk patients.

Fasting and Nonfasting LDL Cholesterol: To Measure or Calculate?

Whether lipid profiles should be measured in the fasting or nonfasting state is a hot topic (1)(2). The fasting state is that used conventionally (3)(4); however, it would be much simpler for patients worldwide if a lipid profile could be taken at any time of the day, irrespective of the time since and the content of the last meal. In both the US and Europe, LDL cholesterol is currently considered the most important measurement in a lipid profile (3)(5). Direct assays for measuring LDL cholesterol are widely available and used in many laboratories; however, even if LDL cholesterol measured with a direct method gives results similar to those calculated with the Friedewald equation, it is unclear how the 2 measurements compare in predicting ischemic cardiovascular disease. In this issue of Clinical Chemistry , Mora et al. report on an evaluation of fasting LDL cholesterol concentrations calculated with the Friedewald equation vs direct measurement of fasting and nonfasting LDL cholesterol concentrations for predicting cardiovascular disease in a prospective study of 27 331 women from the Women’s Health Study (6). They also examined misclassification of individuals into the National Cholesterol Education Program risk categories (3) with direct measurement of LDL cholesterol, compared with conventional Friedewald calculation of LDL cholesterol. These topics are timely and important. In 1972, Friedewald, Levy, and Fredrickson presented a new method for estimating LDL cholesterol and compared it with the gold standard of preparative ultracentrifugation (7). The method required only the measurement of plasma total cholesterol, HDL cholesterol, and triglyceride concentrations—all of which can be measured without the use of laborious and expensive …

Comparison of LDL Cholesterol Concentrations by Friedewald Calculation and Direct Measurement in Relation to Cardiovascular Events in 27 331 Women

National Cholesterol Education Program (NCEP) guidelines recommend development of direct assays for LDL cholesterol (LDL-C) measurement, but it is unclear how these assays compare with Friedewald calculation in predicting cardiovascular disease (CVD). In a study of 27 331 healthy women with triglycerides <or=4.52 mmol/L (<or=400 mg/dL), baseline fasting Friedewald LDL-C was compared with fasting and nonfasting direct homogenous measurement for incident CVD during an 11-year period. Fasting LDL-C measurements obtained by the 2 methods were highly correlated (r = 0.976, P < 0.001). Compared with fasting Friedewald LDL-C, mean fasting direct LDL-C was 0.15 mmol/L (5.6 mg/dL) lower and nonfasting direct LDL-C 0.30 mmol/L (11.5 mg/dL) lower, both P < 0.0001. The adjusted hazard ratio per 1-SD increment was 1.23 [95% CI 1.15-1.32; 1-SD 0.88 mmol/L (34.1 mg/dL)] for fasting direct LDL-C and 1.22 [95% CI 1.14-1.30; 1-SD 0.90 mmol/L (34.9 mg/dL)] for fasting Friedewald. Nonfasting LDL-C was not associated with CVD by either method. Fasting LDL-C measurements fell into the same NCEP risk category with either method for 79.3% of participants, whereas they differed by 1 NCEP category for 20.7% of participants, with most classified into a lower-risk category by direct LDL-C. The association of LDL-C with CVD by the 2 methods was nearly identical in fasting samples. However, the lower direct LDL-C concentrations may misclassify many individuals into a lower NCEP category. Moreover, the lack of association of nonfasting direct LDL-C with CVD raises questions regarding the clinical utility of a direct assay for LDL-C in nonfasting blood samples.

Traditional Clinical Risk Assessment Tools Do Not Accurately Predict Coronary Atherosclerotic Plaque Burden: A CT Angiography Study

The objective of our study was to determine the degree to which Framingham risk estimates and the National Cholesterol Education Program (NCEP) Adult Treatment Panel III core risk categories correlate with total coronary atherosclerotic plaque burden (calcified and noncalcified) as estimated on coronary CT angiograms. Coronary CT angiography was performed in 1,653 patients (1,089 men, 564 women) without a history of coronary heart disease (mean age+/-SD: men, 51.6+/-9.7 years; women, 56.9+/-10.5 years). The most common reasons for the examination were hypercholesterolemia, family history, hypertension, smoking, and atypical chest pain. The coronary tree was divided into 16 segments; four different methods were used to quantify the amount of atherosclerotic plaque or the degree of stenosis in each segment, and segment scores were combined to give total scores. Framingham risk estimates and NCEP risk categories were calculated for each patient. Correlation of plaque scores with the Framingham 10-year risk estimates were modest: Spearman's rho was 0.49-0.55. For all comparisons of NCEP risk categories to plaque score categories, the proportion of raw agreement, p(0), was less than 0.50. Cohen's kappa ranged from 0.18 to 0.20. Overall, 21% of the patients would have their perceived need for statins changed by using the coronary CTA plaque estimates in place of the NCEP core risk categories; 26% of the patients on statins had no detectable plaque. Coronary risk stratification using a risk factor only-based scheme is a weak discriminator of the overall atherosclerotic plaque burden in individual patients. Patients with little or no plaque might be subjected to lifelong drug therapy, whereas many others with substantial plaque might be undertreated or not treated at all.

The comparative effectiveness of rosuvastatin vs. other statins in patients with an increased risk of failure to reach NCEP ATP III goal

Previous studies have demonstrated that failure to reach National Cholesterol Education Program (NCEP) target low-density lipoprotein cholesterol (LDL-C) goal increases the risk of cardiovascular events. Ability to meet goal may be impacted by the choice of statin therapy. This study compares rosuvastatin to other statin therapies among patients presenting with risk factors associated with failure to reach NCEP goal. Retrospective analysis using medical and pharmacy claims linked to laboratory results from a national health plan encompassing private and MedicareAdvantage enrollees age > or = 18 years and newly treated with statins from 1 August 2003 to 28 February 2005. Predictors of failure to reach goal were statin treatment group, age, gender, NCEP risk level, per cent reduction required to attain goal and days from index to LDL-C measurement. Of 11,814 eligible patients, 9.6% were initiated on rosuvastatin, 54.2% atorvastatin, 17.9% simvastatin, 7.1% pravastatin, 2.0% fluvastatin and 9.3% lovastatin. Independent predictors of failure to reach goal included > or = 15% LDL-C reduction required to reach goal, and high and moderate NCEP risk status. In the subset of patients at higher risk of failure to reach goal, rosuvastatin demonstrated a significantly lower rate of failure to achieve goal than atorvastatin, simvastatin, pravastatin, fluvastatin or lovastatin. Real-world factors associated with high risk of failure to reach goal may be used in identifying patients more likely to succeed on rosuvastatin compared with other statins. Low-risk patients needing < 15% LDL-C reduction would be suitable candidates for initiation of most other statins, specifically simvastatin, which has recently become available in the generic form.

Community-Based Provision of Statin and Aspirin After the Detection of Coronary Artery Calcium Within a Community-Based Screening Cohort

We examined the association of coronary artery calcium (CAC) detected on a screening exam with subsequent statin and aspirin usage in a healthy male screening cohort. Whether the presence of CAC, an independent predictor of coronary heart disease outcomes, alters clinical management, such as the use of preventive medications, is unknown. Men (n = 1,640) ages 40 to 50 years (mean 42 years) were screened for coronary heart disease risk factors and CAC. The CAC scores and risk factors were reported to patients, and results were made available in the electronic medical record; however, medications were not prescribed or recommended by the study. During up to 6 years of subsequent annual structured telephone follow-up, we observed the community-based initiation and persistence of aspirin and statin therapy. A progressive increase in the incidence of pharmacotherapy was noted over time such that those with CAC were 3 times more likely to receive a statin (48.5% vs. 15.5%, p < 0.001) and also significantly more likely to receive aspirin (53.0% vs. 32.3%; p < 0.001) than those without CAC. In multivariable models controlling for National Cholesterol Education Program risk variables and baseline medication use, CAC was strongly and independently associated with use of either statin (odds ratio [OR] 3.53; 95% confidence interval [CI] 2.66 to 4.69), aspirin (OR 3.05; 95% CI 2.30 to 4.05) or both (OR 6.97; 95% CI 4.81 to 10.10). In this prospective cohort, the presence of coronary calcification was associated with an independent 3-fold greater likelihood of statin and aspirin usage.

Low-density lipoprotein cholesterol (LDL-C) levels and LDL-C goal attainment among elderly patients treated with rosuvastatin compared with other statins in routine clinical practice

Background: Reducing low-density lipoprotein cholesterol (LDL-C) levels lowers the risk of consequences of cardiovascular disease. Research has confirmed these benefits in elderly patients. The 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (ie, statins) have long-standing proven efficacy in reducing levels of LDL-C and total cholesterol. Objective: The goal of this study was to compare change in LDL-C from baseline and National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III LDL-C goal attainment in a population of elderly patients (aged ≥65 years) treated with rosuvastatin versus other statins in routine clinical practice. Methods: This was a retrospective cohort analysis using medical and pharmacy claims data linked to clinical laboratory results from a large managed care health plan of commercial and Medicare Advantage members in the United States. Included were members aged ≥65 years who were newly treated with statins (index date) from August 1, 2003, through February 28, 2005. All subjects were continuously enrolled for 12 months preindex and ≥30 days postindex, with variable follow-up until therapy discontinuation or end of health plan eligibility. Based on NCEP ATP III guidelines, patients were grouped into risk categories with associated LDL-C goals. The primary outcomes were change in LDL-C from baseline and attainment of NCEP ATP III LDL-C goal among patients not at goal before starting therapy. Generalized linear modeling was used to assess percent change in LDL-C from baseline, controlling for covariates (including age, sex, NCEP risk level, medication possession ratio, preindex LDL-C value, days from index date to postindex LDL-C value, and number of preindex office visits for dyslipidemia). In the subset of patients not at goal before starting therapy, logistic regression was used to estimate the odds of individual patients on other statins reaching goal as compared with rosuvastatin and to produce predicted percent attaining LDL-C goal on individual statins. Results: Of the 2227 elderly new users of statin therapy, 8.0% started on rosuvastatin, 38.9% started on atorvastatin, 3.0% on fluvastatin, 31.0% on lovastatin, 5.5% on pravastatin, and 13.6% on simvastatin. Females comprised 57.7% of the population, and the mean (SD) age was 73 (5.8) years (range, 65–94 years). The mean (SD) doses of rosuvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin were 10.65 (4.59), 16.0 (12.78), 66.31 (23.56), 27.38 (14.07), 32.86 (16.46), and 28.1 (26.2) mg, respectively. After controlling for covariates, rosuvastatin-treated patients had a 35.8% decrease in LDL-C from baseline, which was significantly greater compared with patients in the atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin (29.3%, 21.9%, 22.5%, 22.0%, and 24.9%, respectively; P < 0.05) groups. Atorvastatin (odds ratio [OR], 0.25; 95% CI, 0.12–0.52), fluvastatin (OR, 0.05; 95% CI, 0.02–0.14), lovastatin (OR, 0.10; 95% CI, 0.05–0.20), pravastatin (OR, 0.08; 95% CI, 0.03–0.20), and simvastatin (OR, 0.14; 95% CI, 0.06–0.30) were less likely to attain LDL-C goal compared with rosuvastatin (all, P < 0.001). Predicted percent attaining goal was 93.6% among rosuvastatin users, significantly greater than users of atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin (81.2%, 55.8%, 66.8%, 64.1%, and 72.8%, respectively; P < 0.05). Conclusion: In this elderly patient population, rosuvastatin was a more effective treatment for reducing LDL-C levels and attaining NCEP ATP III LDL-C goals than the other statins.

National Cholesterol Education Program risk assessment and potential for risk misclassification

Background. The National Cholesterol Education Program Adult Treatment Panel report from 2001 (ATP III) recommends clinicians calculate 10-year coronary risk using multivariable methods only for adults with 2 or more risk factors. We aimed to determine who would be falsely classified as low risk using this approach. Methods. We studied 4097 adults aged 20 to 79 years without diagnosed cardiovascular disease or diabetes from the National Health and Nutrition Examination Survey from 1999 to 2002. We determined the proportion with fewer than 2 risk factors who nonetheless had estimated 10-year risk of cardiac death or myocardial infarction ≥ 10% using multivariable methods. Results. Among persons with fewer than 2 risk factors, 5.3% (95% confidence interval 4.7 to 6.1%), had a 10-year risk ≥ 10% using the Framingham Risk Score and would be misclassified using the risk factor counting method (this corresponds to approximately 5,640,000 U.S. adults). Compared to individuals whose classification was unchanged, those misclassified as low risk were older ( P < 0.001) and more likely male (85.5% vs. 41.2%, P < 0.001). Conclusions. Relying on the ATP III risk factor counting method rather than determining risk using multivariable methods in all patients resulted in misclassifiying as low risk over 5 million adults with at least moderately high risk of coronary heart disease, most of whom are middle-aged and older men.

Effects of ezetimibe added to on-going statin therapy on the lipid profile of hypercholesterolemic patients with diabetes mellitus or metabolic syndrome

SUMMARYObjective: To conduct a post-hoc assessment of the lipid-modifying effects of adding the cholesterol absorption inhibitor, ezetimibe, to on-going statin therapy in patients with diabetes mellitus (DM) or metabolic syndrome (MetS).Research design and methods: This was a post-hoc analysis of data from a randomized, double-blind, placebo-controlled trial designed to evaluate the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy and safety of adding ezetimibe 10 mg/day versus placebo to ongoing, open-label statin treatment for 8 weeks in hypercholesterolemic patients. Qualifying LDL-C levels and target LDL-C goals were based on National Cholesterol Education Program risk categories. The DM subgroup were patients who entered the study with a prior diagnosis of DM. Patients were classified as having MetS if they met 3 or more of the following criteria at baseline: triglycerides (TG) ≥ 150 mg/dL (1.69 mmol/L); high-density lipoprotein cholesterol (HDL-C) < 40 mg/dL (1.04 mmol/L) for men or < 50 mg/dL (1.29 mmol/L) for women; fasting serum glucose (FSG) ≥ 110 mg/dL (≥ 6.1 mmol/L); a diagnosis of hypertension or taking hypertension medication or blood pressure ≥ 130/ ≥ 85 mmHg; waist circumference > 88 cm (women) or > 102 cm (men). DM patients were excluded from the MetS subgroup analysis.Main outcome measures: The objectives were to assess the effects of treatment on plasma concentrations of LDL-C and other lipid variables, and on the percentage of patients achieving LDL-C target levels at the end of the study.Results: Of 769 patients enrolled in the original study, there were 191 (24.8%) with DM and 195 (25.4%) with MetS. Regardless of subgroup, ezetimibe + statin was significantly more effective than statin alone at lowering plasma levels of LDL-C, non-HDL-C, total cholesterol, apolipoprotein B, and triglycerides (between-group p < 0.001 for all). For all lipid parameters, the relative treatment effects were generally consistent regardless of DM or MetS status. Significantly more ezetimibe than placebo patients in all subgroups achieved prespecified LDL-C goals ( p < 0.001 for all), and although more patients in the DM and MetS groups, respectively, achieved the goal compared with their non-DM and non-MetS counterparts [83.6% (DM) versus 67.2 (non-DM) and 71.8% (MetS) versus 65.6% (non-MetS)], these differences were not significant after adjusting for differences in baseline LDL-C levels. Ezetimibe was well-tolerated and had a favorable safety profile in all subgroups.Conclusions: The co-administration of ezetimibe with statins, a therapeutic regimen that inhibits both the absorption and synthesis of cholesterol, offers a well-tolerated and efficacious treatment to lower LDL-C in patients with DM and MetS.

Using carotid atherosclerosis as a replacement for age: Effect on national cholesterol education program risk classification

Using carotid atherosclerosis as a replacement for age: Effect on national cholesterol education program risk classification

Metabolic disorders contribute to subclinical coronary atherosclerosis in patients with coronary calcification

This investigation determined the prevalence of low-density lipoprotein (LDL) subclass distribution abnormalities, elevated lipoprotein(a) (Lp(a)), and elevated total plasma homocysteine in asymptomatic subjects with subclinical coronary artery disease determined by electron beam tomography (EBT). Fifty-five percent of subjects were classified as higher risk patients and 45% as lower risk patients, employing the National Cholesterol Education Program (NCEP) lipid criteria. EBT was performed in 296 consecutive asymptomatic subjects, and blood was analyzed for total, LDL, and high-density lipoprotein (HDL) cholesterol, triglycerides, LDL subclass distribution by S3 gradient gel electrophoresis, Lp(a), and total homocysteine. Disorders of LDL subclass distribution were the most common disorder with 60.6% of the population expressing a distribution in the small regions IIIa + IIIb of >20%; and this was more common in the NCEP higher risk group (LDL cholesterol ≥130 and/or HDL cholesterol <35 mg/dl) (p <0.0004). A Lp(a) value >25 mg/dl was found significantly more often in the NCEP higher (36.9%) compared with lower (14.3%) risk group (p <0.001). None of the laboratory measurements correlated with the calcium score or calcium score percentile rank, with the exception of a weak correlation of mean LDL peak particle diameter and calcium percentile (r = 0.14, p = 0.02). Determination of metabolic disorders in addition to LDL cholesterol and HDL cholesterol increased the diagnostic yield from 55.1%, based on NCEP lipid criteria, to 84.1% with the addition of LDL subclass distribution, Lp(a), and total homocysteine. We conclude that: (1) disorders of LDL subclass distribution and elevated Lp(a) occur frequently in NCEP higher risk patients with subclinical coronary artery disease and are the only identifiable disorders in lower NCEP risk patients; and (2) electron beam tomographic evaluation and determination of LDL subclass distribution and Lp(a) should be considered for incorporation into primary prevention guidelines.

Primary prevention of coronary heart disease: guidance from Framingham: a statement for healthcare professionals from the AHA Task Force on Risk Reduction. American Heart Association.

The Framingham Heart Study has contributed importantly to understanding of the causes of coronary heart disease (CHD), stroke, and other cardiovascular diseases. Framingham research has helped define the quantitative and additive nature of these causes or, as they are now called, “cardiovascular risk factors.”1 The National Cholesterol Education Program (NCEP)2 3 has made extensive use of Framingham data in developing its strategy for preventing CHD by controlling high cholesterol levels. The NCEP guidelines2 3 adjust the intensity of cholesterol-lowering therapy with absolute risk as determined by summation of risk factors. The National High Blood Pressure Education Program (NHBPEP) has set forth a parallel approach for blood pressure control. In contrast to the NCEP,2 however, earlier NHBPEP reports issued through the Joint National Committee4 did not match the intensity of therapy to absolute risk for CHD. “Normalization” of blood pressure is the essential goal of therapy regardless of risk status. Blood pressure–lowering therapy is carried out as much for prevention of stroke and other cardiovascular complications as for reduction of CHD risk. Nonetheless, risk assessment could be important for making decisions about type and intensity of therapy for hypertension. Thus, the most recent Joint National Committee report5 gives more attention to risk stratification for adjustment of therapy for hypertension. Although Framingham data have already been influential in the development of national guidelines for risk factor management, the opportunity may exist for both cholesterol and blood pressure programs to draw more extensively from Framingham results when formulating improved risk assessment guidelines and recommending more specific strategies for risk factor modification. The American Heart Association has previously used Framingham risk factor data to prepare charts for estimating CHD risk. Framingham investigators of the National Heart, Lung, and Blood Institute prepared the original charts and have now revised …

Evaluation and Clinical Application of a Direct Low-Density Lipoprotein Cholesterol Assay in Normolipidemic and Hyperlipidemic Adults

This study examines the performance and clinical use of a commercial immunoseparation assay for low-density lipoprotein (LDL) cholesterol in a sample population of normolipidemic and hyperlipidemic adult volunteers. Using paired fasting and nonfasting samples, we compared the direct LDL assay with the β quantification method and the Friedewald calculation. Overall, the direct LDL assay correctly classified 82% and 60% of fasting and nonfasting subjects, respectively, into National Cholesterol Education Program risk groups. The Friedewald method correctly classified 84% of subjects. The fasting direct LDL assay has comparable positive and negative predictive values to the Friedewald method, except at an LDL cholesterol of 100 mg/dl. The nonfasting direct LDL assay demonstrates unacceptable positive predictive values when LDL cholesterol decreases to the 130 to 159 and ≥160 mg/dl categories. Overall, direct LDL assay demonstrates limitations in the nonfasting state and at the LDL cholesterol level of 100 mg/dl used for patients with established coronary heart disease.

Reflotron Performance in a Community Screening Program: Results of the Massachusetts Model Systems for Blood Cholesterol Screening Project

We evaluated the precision, accuracy, and durability of the Reflotron portable analyzer as part of the National Heart, Lung, and Blood Institute's Model Systems for Blood Cholesterol Screening Program. We conducted screenings in a wide variety of settings in four Massachusetts communities over a 16-month period. Fingerstick samples from 10,428 individuals were tested on the Reflotron at the screening sites. For comparison, we drew venous samples from 972 participants and analyzed them in a reference laboratory, which had met the requirements of the Centers for Disease Control's Lipid Standardization Program. All four Reflotrons tested met the 1988 guidelines for precision and accuracy established by the Laboratory Standardization Panel (LSP) of the National Cholesterol Education Program (NCEP). None of the analyzers consistently met the 1992 LSP standards for precision, although two met the 1992 standards for accuracy. More than 40% of Reflotron values differed from the reference laboratory values by more than 5%. As a consequence, more than 16% of individuals were misclassified in terms of the NCEP risk category into which their Reflotron readings fell. All four instruments malfunctioned at some point during the project, precluding their further usage. We recommend improvements in the precision, accuracy, and durability of this analyzer.

The Accuracy of Portable Cholesterol Analyzers in Public Screening Programs

To determine the accuracy of portable cholesterol analyzers in public settings, four screening organizations were accompanied to cholesterol screenings where consenting participants completed the finger-stick procedure and provided a blood sample by venipuncture. The finger-stick values were compared later with the participants' blood cholesterol values obtained in a reference laboratory. The results indicated that only one of the organizations produced cholesterol measurements entirely within the acceptable range (+/- 14.2%), while the accuracy of the other three organizations ranged from 76.5% to 96.4%. Those finger-stick values that did not fall within the acceptable range tended to underestimate the laboratory cholesterol values. Additionally, classification of the persons screened based on the National Cholesterol Education Program risk categories indicated that the finger-stick values primarily tended to produce false-negative results. The variability of the results across organizations was caused partially by insufficient operator training. However, inadequate quality-control procedures for field settings and dilution of capillary blood by tissue fluid also may have contributed to the inaccurate finger-stick results.

Progress in Lipid Reporting Practices and Reliability of Blood Cholesterol Measurement in Clinical Laboratories in Nebraska

The National Cholesterol Education Program has recommended that all laboratories be consistent, precise, and accurate in the reporting and measurement of blood cholesterol levels. In a follow-up to a 1984 survey study, we assessed the changes in reporting procedures for measurements of blood lipid levels in 16 clinical laboratories in Nebraska. Using human serum reference materials of known cholesterol concentrations provided by the Centers for Disease Control, we also assessed the precision and accuracy of measurement of blood cholesterol levels in clinical laboratories in Nebraska. Fourteen of the 16 laboratories restudied in 1987 had altered the reference range for total serum cholesterol since 1984, 86% of whom lowered the upper limit of the reference range. Eleven of 16 laboratories expressed reference ranges for total serum cholesterol in terms of patient age in 1987, while only 7 of 20 did in 1984. Gender-based reference ranges increased from 0 to 5 from 1984 to 1987. Similar trends were seen in the reporting of high-density lipoprotein cholesterol and triglyceride concentrations. Reporting procedures varied greatly; only 1 laboratory used National Cholesterol Education Program risk levels for measuring total serum cholesterol levels. Fifteen laboratories met the National Cholesterol Education Program recommendation for precision (coefficient of variation, less than or equal to 5%) and 78% of laboratories obtained results that satisfied the current recommendation for accuracy (within 5% of "true value," as determined by the Centers for Disease Control).