A comparison of HDL and LDL cholesterol for prevalent coronary calcification

BACKGROUND: Coronary calcification is a marker for coronary atherosclerosis. It has been postulated that high levels of high density lipoprotein cholesterol (HDL-C) are associated with a reduced amount of atherosclerotic disease while previous reports have found a lack of association between low density lipoprotein cholesterol (LDL-C) and coronary calcification (CAC). The purpose of this study was to compare the correlation and predictive power of HDL-C with LDL-C for prevalent coronary calcification. METHODS: A total of 6093 subjects were studied with respect to coronary calcification, serum cholesterol indices, personal health history and body morphology. Analyses consisted of correlation coefficients, logistic regression and sensitivity analysis to determine the strength of association between HDL-C and coronary calcification after controlling for covariates. RESULTS: The correlation between HDL-C and coronary calcium score (CCS) was three times that of LDL-C. Individuals with an HDL-C level <40 mg/dl had significantly higher calcium scores while increases in HDL-C were associated with a significant reduction in risk for the presence of any calcified plaque. Results of multivariate logistic regression revealed that HDL-C is predictive of calcified plaque development independent of LDL-C. Sensitivities and positive predictive values for both HDL-C and LDL-C were low. CONCLUSIONS: Increasing levels of HDL-C were associated with less coronary calcification and a smaller probability of having any calcified disease supporting the antiatherogenic hypothesis for HDL-C. HDL-C predicts the presence of any calcified atherosclerotic plaque independently of LDL-C. However, neither parameter seems suitable as a screening tool for predicting prevalent calcified atheromatous disease.     

Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome.

PURPOSE: Women with polycystic ovary syndrome are hyperandrogenemic and insulin resistant, which are associated with alterations in circulating lipid and lipoprotein levels. We sought to determine the prevalence of, and risk factors for, lipid abnormalities in these women. SUBJECTS AND METHODS: Non-Hispanic white women with polycystic ovary syndrome (n = 195) and ethnically matched control women (n = 62) had fasting blood obtained for hormone and lipid levels. Subjects were categorized by body mass index (nonobese <27 kg/m(2), obese > or =27 kg/m(2)), and analyses were adjusted for age. RESULTS: Total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels increased significantly in obese women with polycystic ovary syndrome (n = 153) compared with obese control women (n = 35; mean difference in total cholesterol level = 29 mg/dL; 95% confidence interval [CI]: 14 to 45 mg/dL; P <0.001; mean difference in LDL-C level = 16 mg/dL; 95% CI: 4 to 30 mg/dL; P = 0.006). Similarly, total cholesterol and LDL-C levels increased significantly in nonobese women with polycystic ovary syndrome (n = 42) compared with nonobese control women (n = 27; mean difference in total cholesterol = 32 mg/dL; 95% CI: 13 to 52 mg/dL; P <0.001; mean difference in LDL-C level = 32 mg/dL; 95% CI: 15 to 52 mg/dL; P <0.001). In obese women, high-density lipoprotein cholesterol (HDL-C) and triglyceride levels increased significantly in women with polycystic ovary syndrome compared with control women (mean difference in HDL-C level = 6 mg/dL; 95% CI: 2 to 12 mg/dL; P = 0.002; mean difference in triglyceride level = 34 mg/dL; 95% CI: 1 to 77 mg/dL; P = 0.04). Differences in LDL-C and HDL-C levels, but not triglyceride levels, remained significant after adjusting for alcohol intake, smoking, and exercise. Although age, body mass index, and polycystic ovary syndrome status were significant predictors of lipid levels, these factors accounted for no more than 25% of the variance. CONCLUSIONS: In this large study of non-Hispanic white women, elevations in LDL-C levels were the predominant lipid abnormality in women with polycystic ovary syndrome, independent of obesity. The characteristic dyslipidemia of insulin resistance was absent. Indeed, obese women with polycystic ovary syndrome had relatively elevated HDL-C levels, which may confer some protection against cardiovascular disease.     

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

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

Lipid changes on hormone therapy and coronary heart disease events in the Heart and Estrogen/progestin Replacement Study (HERS)

Background

Despite the effect of lowering low-density lipoprotein cholesterol (LDL-C) levels and raising high-density lipoprotein cholesterol (HDL-C) levels, combination hormone therapy did not reduce the incidence of coronary heart disease (CHD) events in the Heart and Estrogen/progestin Replacement Study (HERS). To explore possible mechanisms, we examined the association between lipid changes and CHD outcomes among women assigned to hormone therapy.

Methods

HERS participants were postmenopausal women with previously diagnosed CHD who were randomly assigned to receive conjugated estrogens and medroxyprogesterone or identical placebo and then followed-up for an average of 4.1 years. Among women assigned to hormone therapy, associations between baseline-to-year-1 lipid level changes and CHD events were compared with the associations observed for baseline lipids using multivariate proportional hazards models.

Results

Among women assigned to hormone therapy, CHD events were independently predicted by baseline LDL-C levels (relative hazard [RH] 0.94 per 15.6 mg/dL decrease, 95% CI 0.88-1.01) and HDL-C levels (RH 0.89 per 5.4 mg/dL increase, 95% CI 0.81-0.99), but not by triglyceride levels (RH 1.01 per 13.2mg/dL increase, 95% CI 0.97-1.06). CHD events were marginally associated with first-year reductions in LDL-C levels (RH 0.95 per 15.6mg/dL decrease, 95% CI 0.86-1.04), and were not associated with increases in HDL-C levels ( RH 1.03 per 5.4 mg/dL increase, 95% CI 0.91-1.16) or triglyceride levels (RH 1.01 per 13.2 mg/dL increase, 95% CI 0.98-1.05).

Conclusion

Changes in lipid levels with hormone therapy are not predictive of CHD outcomes in women with heart disease in the HERS trial.     

Coronary artery calcification in black women and white women

Background Coronary calcification is a potent independent predictor of coronary risk. Sex-specific risk categories based on calcium scores have been established, but ethnic differences in coronary calcification have been little studied. This prospective cohort study compares coronary calcification, assessed by computed tomography, in postmenopausal black women and white women. Methods and Results Computed tomographic scans were performed on 128 black women and 733 white women without known coronary artery disease (mean age 63 ± 8 years). Although coronary risk factors were more prevalent among black women (P < .0001), total calcium scores were similar to those in white women. By use of the Framingham algorithm, higher calcium scores were associated with higher 10-year risk of myocardial infarction or coronary death. In multiple regression analysis, age was independently associated with higher calcium scores in both ethnic groups (P = .002 for black women, P < .0001 for white women). Diabetes mellitus and not exercising at least 3 times per week were independently associated with higher calcium scores in white women but not black women. Educational level, body mass index, current hormone replacement therapy, hysterectomy, dietary fat consumption, family history of premature coronary disease, hypertension, self-reported high cholesterol, and current smoking were not independently associated with coronary calcium score in black women, white women, or the combined cohort; neither was ethnicity an independent predictor of coronary calcification. Conclusions Despite higher dietary fat consumption, higher body mass index, and greater prevalence of hypertension, diabetes, and smoking, black women had coronary calcium scores similar to those of white women. Ethnicity was not an independent predictor of coronary calcification. (Am Heart J 2003;145:724-9.)     

Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study)

International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides for patients at moderately high to high coronary heart disease (CHD) risk. Combination therapy is often required to achieve multiple lipid treatment goals, and > or =50% reduction in low-density lipoprotein cholesterol (LDL-C) is needed in some patients to achieve aggressive LDL-C targets. In this context, we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin (niacin ER), a statin plus ezetimibe, and a highly potent statin alone. This was an open-label, multicenter, 12-week study in 292 patients (50% women) who qualified for drug therapy based on number of CHD risk factors. Patients were randomized to four parallel arms, titrated from low to moderate or high doses: atorvastatin/niacin ER, rosuvastatin/niacin ER, simvastatin/ezetimibe, or rosuvastatin alone. Baseline mean values were, for LDL-C 197 mg/dL (5.1 mmol/L), HDL-C 49 mg/dL (1.3 mmol/L), triglycerides 168 mg/dL (1.9 mmol/L). There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment. All groups lowered LDL-C by approximately 50% or more (range -49 to -57%), achieving mean levels of 82-98 mg/dL (2.1-2.5 mmol/L). Changes in non-HDL-C (range -46 to -55%) mirrored those for LDL-C and did not differ among treatment groups. Statin/niacin ER combination regimens also increased HDL-C and large HDL (HDL2) and lowered triglycerides and lipoprotein (a) significantly more than other regimens. No drug-related myopathy or hepatotoxicity was observed. In this study, low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD.     

Thyroid Function and Serum Lipids in Older Women: A Population-based Study

Purpose: To determine if thyroid hormone deficiency, manifested by elevated serum thyrotropin (TSH), is associated with alterations in serum lipids in an unselected population of older women.Subjects and Methods: Population-based sampling of 279 ambulatory white women over age 65 studied at four US clinical centers, randomly selected from a cohort of 9,704 participants enrolled in the Study of Osteoporotic Fractures. A third-generation chemiluminescent TSH assay and serum lipid levels—total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides—were measured on fasting sera collected at the baseline visit. The cross-sectional relationships between TSH and lipid levels were analyzed.Results: TSH was high (>5.5 mU/L) in 19 women (6.8%), and was low (≤0.1 mU/L) in 10 (3.6%). After multiple adjustment, LDL-C was 17 mg/dL or 13% higher (95% confidence interval [CI] 1%, 25%), and HDL-C was 6.5 mg/dL or 12% lower (CI −0.2%, −25%) in women with high TSH compared with those with normal TSH. The ratio of LDL-C to HDL-C was 29% greater (CI 4%, 53%) among women with elevated TSH. Although total cholesterol was 8% higher among women with high TSH, this difference was not statistically significant (CI −1%, 15%). High TSH was found in 12% of the women with the combination of high cholesterol (>240 mg/dL), high LDL-C (>160 mg/dL), and low HDL-C (<45 mg/dL); likelihood ratio = 1.8) whereas high TSH was found in only 2.2% of women with normal lipids (likelihood ratio = 0.3).Conclusion: Among older white women, high TSH is associated with deleterious changes in serum lipids, particularly HDL-C, LDL-C, and the ratio of LDL-C to HDL-C cholesterol. Women with multiple lipid abnormalities are twice as likely to have an increased TSH.     

Establishing the benefit of statins in low-to-moderate--risk primary prevention: the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)

AFCAPS/TexCAPS was the first prevention trial of a statin conducted in a low-to-moderate-risk cohort that included men (> or =45 years) and women (> or =55 years) with no evidence of atherosclerotic cardiovascular disease. At study entry, LDL-C had to be 130-190 mg/dL and HDL-C < or =45 mg/dL for men and < or =47 mg/dL for women. Participants were randomized to either lovastatin 20-40 mg/day (n=3304) or placebo (n=3301) for a mean follow-up period of 5.2 years. At 1 year, in the lovastatin group TC, LDL-C, and TG were reduced by 18.4%, 25.0%, and 15%, respectively. HDL-C increased by 6.0%. At 5 years, there was a 37% decrease in the relative risk for having a first acute coronary event in the lovastatin versus placebo group. Women showed similar relative risk reduction as men. Older individuals benefited as much as younger ones from lovastatin. Subjects with > or =2 risk factors benefited more from statin than those with <2 risk factors. At baseline, HDL-C but not TC or LDL-C was determined a significant predictor of risk. On treatment, ApoB and ApoA1 were the best predictors. Based on AFCAPS/TexCAPS, a simple heuristic could be that individuals with "age plus one other risk factor" may benefit from statin therapy in primary prevention.     

Effects of pravastatin on coronary events in 2073 patients with low levels of both low-density lipoprotein cholesterol and high-density lipoprotein cholesterol: results from the LIPID study.

AIMS: Fibrates or nicotinic acid are usually recommended for secondary prevention of coronary heart disease in patients with low plasma levels of both low-density lipoprotein cholesterol (LDL-C) < or =140 mg/dL (< or =3.6 mmol/L) and high-density lipoprotein cholesterol (HDL-C) < or =40 mg/dL (< or =1.03 mmol/L). The LIPID trial, a randomised, placebo-controlled trial in 9014 patients at 87 centres in Australia and New Zealand, provided an opportunity to investigate the effects of an HMG-CoA reductase inhibitor in patients with low LDL-C and low HDL-C. METHODS AND RESULTS: Participants in this post hoc substudy were 2073 patients aged 31-75 years with baseline LDL-C < or =140 mg/dL (< or =3.6 mmol/L), HDL-C < or =40 mg/dL (< or =1.03 mmol/L), and triglyceride < or =300 mg/dL (< or =3.4 mmol/L). The relative risk reduction with pravastatin treatment was 27% for major coronary events (95% CI 8-42%), 27% for coronary heart disease mortality (95% CI 0-47%), 21% for all-cause mortality (95% CI 0-38%), and 51% for stroke (95% CI 24-69%). The number needed to treat to prevent a major coronary event over 6 years was 22. CONCLUSIONS: Treatment with pravastatin in patients with both low LDL-C and low HDL-C significantly reduced major coronary events, stroke, and all-cause mortality. The level of HDL-C is crucial to the risk of recurrent CHD events and, consequently, the benefit of lowering LDL-C.     

Increased serum lipids are associated with higher CD4 lymphocyte count in HIV-infected women

OBJECTIVE: Highly active antiretroviral therapy (HAART) has been associated with dyslipidaemia; however, the roles of immune status and non-HIV-disease risk factors remain unclear. METHODS: A cross-sectional analysis of fasting lipids was carried out for 231 women, of whom 132 were HIV-infected and 99 were uninfected. The concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B (apo B) were measured. CD4 lymphocyte count, hepatitis C status, demographics, diet, and anthropometrics were also assessed. RESULTS: A total of 132 women were HIV-infected [30 were antiretroviral-naive, 68 were on protease inhibitors (PIs), and 34 were on non-PI HAART]. HIV infection was associated with higher triglycerides, lower HDL-C, and, among obese women, higher total cholesterol and LDL-C. Non-PI and PI HAART were each independently associated with higher total cholesterol, LDL-C, and apo B, compared with being ART-naive. Among HIV-infected women, after adjustment for HAART use, women with a CD4 lymphocyte count > or =500 cells/microL had total cholesterol 41.8 mg/dL (P = 0.002) and LDL-C 28.8 mg/dL (P = 0.01) higher, on average, than women with a CD4 count <200 cells/microL. Women with a CD4 count of 200-499 cells/microL had total cholesterol 26.31 mg/dL higher, on average, than those with a CD4 count <200 cells/microL (P = 0.04), although differences in LDL-C did not reach significance (15.51 mg/dL; P = 0.12). A higher CD4 count was also associated with higher apo B (P < 0.001). Active hepatitis C infection was associated with lower total cholesterol, LDL-C, triglycerides, and apo B. CONCLUSIONS: Higher CD4 lymphocyte counts were associated with higher lipid levels, suggesting that immune competence may independently affect the dyslipidaemia seen in the HAART era. In addition, it is important that hepatitis C status be assessed in studies of dyslipidaemia in the HIV-infected population.     

Coronary and aortic calcification in women with a history of major depression

BACKGROUND: Although depression is a well-documented risk factor for clinical heart disease, its association with subclinical atherosclerosis is unclear. We hypothesized that middle-aged women with a history of recurrent major depression would show evidence of atherosclerosis. METHODS: Coronary and aortic calcification was measured by electron beam tomography in 58 African American and 152 white healthy middle-aged women. Women were administered the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and a self-report measure of current depressive symptoms. RESULTS: Coronary calcification was found in 103 women (49%) and aorta calcification in 144 women (54%); high calcification scores were set at approximately 75% of the sample distribution (ie, at >/=10 for the coronary calcium score [n = 49 women] and at >100 for the aorta calcium score [n = 53 women]). Women with a history of recurrent major depression (n = 53) were more likely to have any coronary calcification or calcification in the high category at either site compared with women with a history of a single episode of depression or no depression. After stepwise forward adjustment for cardiovascular risk factors and sociodemographic characteristics, a history of recurrent major depression, compared with a single episode or no history, was associated with odds ratios (ORs) of 2.46 (95% confidence interval [CI], 1.06-5.67) for any coronary calcification, 2.71 (95% CI, 1.08-6.81) for high coronary calcification, and 3.39 (95% CI, 1.34-8.63) for high aortic calcification. Further adjustments for waist-hip ratio reduced the association between history of recurrent depression and any calcification (OR, 2.24; 95% CI, 0.94-5.32) and high calcification (OR, 2.31; 95% CI, 0.89-5.99). CONCLUSIONS: In this sample of asymptomatic middle-aged women without known coronary disease, recurrent major depression was independently associated with coronary and aortic calcification. Waist-hip ratio in part mediated the association. Our findings suggest that recurrent major depression may be a risk factor for early atherosclerosis in women.     

The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study

OBJECTIVES: To assess the association between lipid levels and cardiovascular events in older adults. DESIGN: A prospective population-based study. SETTING: Four field centers in U.S. communities. PARTICIPANTS: A total of 5,201 adults aged 65 and older living in U.S. communities, plus a recruitment of 687 African Americans 3 years later. MEASUREMENTS: Fasting lipid measures included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides. RESULTS: At baseline, 1,954 men and 2,931 women were at risk for an incident myocardial infarction (MI) or stroke. During an average 7.5-year follow-up, 436 subjects had a coronary event, 332 had an ischemic stroke, 104 a hemorrhagic stroke, and 1,096 died. After adjustment, lipid measures were not major predictors of the outcomes of MI, ischemic stroke, hemorrhagic stroke, and total mortality. For total cholesterol and LDL-C, the associations with MI and ischemic stroke were only marginally significant. HDL-C was inversely associated with MI risk (hazard ratio=0.85 per standard deviation of 15.7 mg/dL, 95% confidence interval=0.76-0.96). For the outcome of ischemic stroke, high levels of HDL-C were associated with a decreased risk in men but not women. Lipid measures were generally only weakly associated with the risks of hemorrhagic stroke or total mortality. CONCLUSION: In this population-based study of older adults, most lipid measures were weakly associated with cardiovascular events. The association between low HDL-C and increased MI risk was nonetheless strong and consistent.     

Coronary calcification in body builders using anabolic steroids

The authors measured coronary artery calcification as a means of examining the impact of anabolic steroids on the development of atherosclerotic disease in body builders using anabolic steroids over an extended period of time. Fourteen male professional body builders with no history of cardiovascular disease were evaluated for coronary artery calcium, serum lipids, left ventricular function, and exercise-induced myocardial ischemia. Seven subjects had coronary artery calcium, with a much higher than expected mean score of 98. Six of the 7 calcium scores were >90th percentile. Mean total cholesterol was 192 mg/dL, while mean high-density lipoprotein was 23 mg/dL and the mean ratio of total cholesterol to high-density lipoprotein was 8.3. Left ventricular ejection fraction ranged between 49% and 68%, with a mean of 59%. No subject had evidence of myocardial ischemia. This small group of professional body builders with a long history of steroid abuse had high levels of coronary artery calcium for age. The authors conclude that in this small pilot study there is an association between early coronary artery calcium and long-term steroid abuse. Large-scale studies are warranted to further explore this association.     

Risk determination of dyslipidemia in populations characterized by low levels of high-density lipoprotein cholesterol

Background

Current guidelines for managing dyslipidemia qualify patients for treatment based on low-density lipoprotein cholesterol (LDL-C) levels and other risk factors for coronary heart disease (CHD). However, when LDL-C is the sole lipid criterion for initiating therapy, patients with levels below the treatment initiation threshold who are at high risk because of low levels (<40 mg/dL) of high-density lipoprotein cholesterol (HDL-C) might not be identified. Twenty percent of male patients with CHD in the United States fall into this category. The total cholesterol/HDL-C (TC/HDL-C) ratio predicts CHD risk regardless of the absolute LDL-C and HDL-C.

Methods

We compared guidelines based on TC/HDL-C and LDL-C with those recommended by the National Cholesterol Education Program Adult Treatment Panel III (ATP III). Both sets of guidelines were applied to 9837 adults (>20 years of age) in the Turkish Heart Study, which has shown that 75% of men and 50% of women in Turkey have HDL-C <40 mg/dL.

Results

ATP III guidelines identified 14% of Turkish adults, 20 years or older, as candidates for lifestyle treatment only and an additional 18% for drug treatment. In conjunction with ATP III LDL-C thresholds, the TC/HDL-C ratio (>3.5, patients with CHD; ≥6.0, 2+ risk factors, ≥7.0, 0 to 1 risk factor) assigned lifestyle therapy alone to 18% and drug treatment to an additional 36%. Among primary prevention subjects at high risk because of age (men ≥45 years; women ≥55 years), both sets of guidelines prescribed lifestyle therapy for only 5%; however, drug treatment was recommended for an additional 13% by ATP III guidelines and an additional 18% by TC/HDL-C and LDL-C.

Conclusions

In populations at risk for CHD caused by low HDL-C, qualification of subjects for treatment based on either the TC/HDL-C ratio or LDL-C thresholds identifies more high-risk subjects for treatment than LDL-C threshold values alone, and use of the ratio, instead of risk tables, simplifies the approach for physicians.     

Prevalence and phenotypic distribution of dyslipidemia in type 1 diabetes mellitus: effect of glycemic control

BACKGROUND: Data on the prevalence of dyslipidemia in type 1 diabetes mellitus are scarce and are based on total triglyceride and total cholesterol concentrations alone. OBJECTIVE: To assess the effect of glycemic optimization on the prevalence of dyslipidemia and low-density lipoprotein cholesterol (LDL-C) concentrations requiring intervention in patients with type 1 diabetes. PATIENTS: A total of 334 adults with type 1 diabetes and 803 nondiabetic control subjects. METHODS: Levels of glycosylated hemoglobin, total cholesterol, total triglyceride, high-density lipoprotein cholesterol (HDL-C), and LDL-C were assessed at baseline and after 3 to 6 months of intensive therapy with multiple insulin doses. RESULTS: Levels of LDL-C greater than 4.13 mmol/L (>160 mg/dL) and total triglyceride greater than 2.25 mmol/L (>200 mg/dL) and low HDL-C levels (<0.9 mmol/L [<35 mg/dL] in men or <1.1 mmol/L [<45 mg/dL] in women) were found in 16%, 5%, and 20% of patients and 13%, 6%, and 9% of controls, respectively (P<.001 for HDL-C). Diabetic women showed more hypercholesterolemia than nondiabetic women (15.6% vs 8.5%; P =.04). After glycemic optimization (mean +/- SD glycosylated hemoglobin decrease, 2.2 +/- 1.96 percentage points), the prevalence of LDL-C levels greater than 4.13 mmol/L (>160 mg/dL) became lower in diabetic men than in nondiabetic men (9.7% vs 17.5%; P =.04), but women showed frequencies of dyslipidemia similar to their nondiabetic counterparts. The proportion of patients with LDL-C concentrations requiring lifestyle (>2.6 mmol/L [>100 mg/dL]) or drug (>3.4 mmol/L [>130 mg/dL]) intervention decreased from 78% and 42% to 66% and 26%, respectively. CONCLUSIONS: Low HDL-C is the most frequent dyslipidemic disorder in patients with poorly controlled insulin-treated type 1 diabetes, and a high proportion show LDL-C levels requiring intervention. Less favorable lipid profiles could explain the absence of sex protection in diabetic women. The improvement caused by glycemic optimization puts forward intensive therapy as the initial treatment of choice for dyslipidemia in poorly controlled type 1 diabetes.     

Lack of association of lipoprotein(a) levels with coronary calcium deposits in asymptomatic postmenopausal women

OBJECTIVES: This study sought to determine the relationship of lipoprotein(a) (Lp(a)) and other cardiac risk factors to coronary atherosclerosis as measured by calcification of coronary arteries in asymptomatic postmenopausal women. BACKGROUND: Lipoprotein(a) is considered a risk factor for coronary heart disease. Coronary calcium deposition is believed to be a useful noninvasive marker of coronary atherosclerosis in women. However, to our knowledge, there are no reports of the relationship of Lp(a) to coronary calcium in postmenopausal women. METHODS: In 178 asymptomatic postmenopausal women (64 +/- 8 years), we measured Lp(a) and other cardiac risk factors: age, hypertension, diabetes, low-density lipoprotein cholesterol, smoking status, body mass index, physical activity level and duration of hormone replacement therapy. Electron-beam computed tomography was done to measure coronary calcium (calcium score). We analyzed the relationship between calcium score and cardiac risk factors using multivariate analysis. RESULTS: Although calcium score correlated with traditional risk factors of age, diabetes, hypertension and smoking, it did not correlate with Lp(a) in the asymptomatic postmenopausal women. Similar multivariate analyses were done in the subjects age >60 years and in the subjects with significant coronary calcium deposit (calcium score > or =50). These analyses also have failed to show an association of levels of Lp(a) with coronary calcium deposits. CONCLUSIONS: We conclude that in asymptomatic postmenopausal women, Lp(a) levels do not correlate with coronary atherosclerosis as measured by coronary calcium deposits.     

Comparison of high-density and low-density lipoprotein cholesterol subclasses and sizes in Asian Indian women with Caucasian women from the Framingham Offspring Study

BACKGROUND: Asian Indian women have a higher rate of coronary artery disease (CAD) than do other ethnic groups, despite similar conventional risk factors and lipid profiles. Smaller high-density lipoprotein cholesterol (HDL-C) particle size is associated with reduced cardiac protection or even an increased risk of CAD. Exceptional longevity correlates better with larger HDL-C particle sizes. HYPOTHESIS: Higher rates of CAD among Asian Indian women may partly be explained by the differenes in the prevalence of atherogenic HDL-C and low-density lipoprotein cholesterol (LDL-C) sizes and their subclass concentrations among Asian Indian women compared with Caucasian women. METHODS: We measured HDL-C concentrations and sizes by nuclear magnetic resonance spectroscopy in 119 relatively healthy Asian Indian women and compared them with those of 1752 Caucasian women from the Framingham Offspring Study (FOS). RESULTS: Asian Indian women were significantly younger (47.9 +/- 11.2 vs. 51.0 +/- 10.1 years, p = 0.0001), leaner (body mass index 24.0 +/- 4.7 vs. 26.0 +/- 5.6, p = < 0.0002), less likely to be postmenopausal (32 vs. 54%, p = < 0.0001), or smoke (< 1 vs. 20%, p = < 0.0001); nevertheless, prevalence of CAD was higher in Asian Indian women (4.2 vs. 1%, p = 0.0006). Asian Indian women had similar HDL-C (53 +/- 13 vs. 53 +/- 13 mg/dl, p = 0.99), smaller HDL-C particle size (8.9 +/- 0.35 vs. 9.4 +/- 0.44 nm, p = < 0.0001), higher total cholesterol (209 +/- 40 vs. 199 +/- 42 mg/dl, p = 0.01), and similar triglyceride (120 +/- 77 vs. 108 +/- 110 mg/d, p = 0.24) levels. Low-density lipoprotein cholesterol, particle concentrations and sizes, as well as prevalence of pattern B were similar. CONCLUSIONS: Compared with the FOS, Asian Indian women have significantly smaller overall HDL particle size and similar levels of HDL-C, which may reflect impaired, reverse cholesterol transport. Total cholesterol was higher, whereas triglyceride and LDL-C levels were similar. This may partly explain the higher CAD rates in Asian Indian women. Further large scale, prospective, long-term studies are warranted.     

Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines

The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.     

Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines

The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.     

Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines

The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C < 100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.