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.     

Effectiveness of statin therapy in adults with coronary heart disease

BACKGROUND: We conducted a meta-analysis of patients with coronary heart disease (CHD) to determine the effectiveness of statin therapy; whether effectiveness varied according to patient characteristics, outcomes, or pretreatment low-density lipoprotein cholesterol (LDL-C) levels; and the optimal LDL-C goal and the level at which to initiate statin therapy. METHODS: Randomized trials or systematic reviews for secondary prevention of CHD with statin therapy published between January 1966 and December 2002 were identified through MEDLINE and the Cochrane Library. Studies were included if they randomly assigned adults with CHD to statin therapy or control, enrolled at least 100 individuals per arm, reported clinical outcomes and LDL-C levels, and were published as full studies in English. Two reviewers abstracted data using a prospectively designed protocol. RESULTS: Twenty-five studies enrolling 69 511 individuals were included. Participants in 19 placebo-controlled trials had a mean age of 63 years and a mean pretreatment LDL-C level of 149 mg/dL (3.85 mmol/L); 23% were women. Statin therapy reduced CHD mortality or nonfatal myocardial infarction 25% (relative risk [RR], 0.75; 95% confidence interval [CI], 0.71-0.79), all-cause mortality 16% (RR, 0.84; 95% CI, 0.79-0.89), and CHD mortality 23% (RR, 0.77; 95% CI, 0.71-0.83). Beneficial effects were seen in women and the elderly. There were no data to determine whether lowering the LDL-C level to less than 100 mg/dL (<2.59 mmol/L) was superior to lowering it to 100 to 130 mg/dL (2.59-3.36 mmol/L). Meta-regression analyses revealed risk reductions for CHD mortality or nonfatal myocardial infarction and major vascular events across available pretreatment LDL-C levels. CONCLUSION: Statin therapy reduces mortality and morbidity in adults with CHD, even at pretreatment LDL-C levels as low as 100 mg/dL (2.59 mmol/L).     

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.     

Can change in high-density lipoprotein cholesterol levels reduce cardiovascular risk?

Background

The cardiovascular risk reduction observed in many trials of lipid-lowering agents is greater than expected on the basis of observed low-density lipoprotein cholesterol (LDL-C) level reductions. Our objective was to explore the degree to which high-density lipoprotein cholesterol (HDL-C) level changes explain cardiovascular risk reduction.

Methods

A systematic review identified trials of lipid-lowering agents reporting changes in HDL-C and LDL-C levels and the incidence of coronary heart disease (CHD). The observed relative risk reduction (RRR) in CHD morbidity and mortality rates was calculated. The expected RRR, given the treatment effect on total cholesterol level, was calculated for each trial with logistic regression coefficients from observational studies. The difference between observed and expected RRR was plotted against the change in HDL-C level, and a least-squares regression line was calculated.

Results

Fifty-one trials were identified. Nineteen statin trials addressed the association of HDL-C with CHD. Limited numbers of trials of other therapies precluded additional analyses. Among statin trials, therapy reduced total cholesterol levels as much as 32% and LDL-C levels as much as 45%. HDL-C level increases were <10%. Treatment effect on HDL-C levels was not a significant linear predictor of the difference in observed and expected CHD mortality rates, although we observed a trend in this direction (P = .08). Similarly, HDL-C effect was not a significant linear predictor of the difference between observed and expected RRRs for CHD morbidity (P = .20).

Conclusions

Although a linear trend toward greater risk reduction was observed with greater effects on HDL-C, differences were not statistically significant. The narrow range of HDL-C level increases in the statin trials likely reduced our ability to detect a beneficial HDL-C effect, if present.     

Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin

Background

Despite the efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C) levels, many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction. The cholesterol absorption inhibitor, ezetimibe, has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins. This study was performed to compare the efficacy and safety of ezetimibe (10 mg) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease (CHD) and are not at their LDL-C goal on the starting dose of atorvastatin.

Methods

This was a 14-week, multicenter, randomized, double-blind, active-controlled study conducted in 113 clinical research centers in 21 countries. Participants were adults with heterozygous familial hypercholesterolemia (HeFH), CHD, or multiple (≥2) cardiovascular risk factors, and a LDL-C level ≥130 mg/dL after a 6- to10-week dietary stabilization and atorvastatin (10 mg/day) open-label run-in period. Eligible subjects continued to receive atorvastatin (10 mg) and were randomized to receive blinded treatment with ezetimibe (10 mg/day; n = 305) or an additional 10 mg/day of atorvastatin (n = 316). The atorvastatin dose in both groups was doubled after 4 weeks, 9 weeks, or both when the LDL-C level was not at its goal (≤100 mg/dL), so that patients receiving combined therapy could reach 40 mg/day and patients receiving atorvastatin alone could reach 80 mg/day. The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14. A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy.

Results

The proportion of subjects reaching their target LDL-C level goal of ≤100 mg/dL was significantly higher in the co-administration group than in the atorvastatin monotherapy group (22% vs 7%; P <.01). At 4 weeks, levels of LDL-C, triglycerides, and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin (LDL-C −22.8% versus −8.6%; P <.01). The combination regimen had a safety and tolerability profile similar to that of atorvastatin alone.

Conclusions

The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone.     

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.     

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.     

Coronary and aortic calcification among women 8 years after menopause and their premenopausal risk factors : the healthy women study.

In the Healthy Women Study, the relationship between cardiovascular risk factors measured premenopausally at age 48, use of hormone therapy, and coronary and aortic calcification at age 58 were evaluated among 169 women. Approximately 63% of women had no coronary calcification, but only 29% had no aortic calcification. Coronary calcification and aortic calcification were positively correlated with each other. There was a very strong association between low density lipoprotein cholesterol (LDL-C) level and coronary calcification. Among women with premenopausal levels of LDL-C <100 mg/dL, only 9% had a coronary calcium score >/=101 compared with 30% of women with an LDL-C >160 mg/dL. Only 5% of women with a high density lipoprotein cholesterol (HDL-C) level >60 mg/dL had high coronary scores. The level of HDL(2)-C was especially strongly inversely related to coronary calcium scores. Cigarette smoking was a very important determinant of both high aortic and high coronary calcium scores. Other risk factors associated with greater coronary calcium were higher systolic blood pressure, triglycerides levels, and blood glucose. Use of hormone replacement therapy was associated with less coronary calcium (NS). For both hormone replacement therapy users and nonusers, the levels of LDL-C and HDL-C measured premenopausally were predictors of coronary and aortic calcium scores. Thus, risk factors evaluated premenopausally are powerful predictors of coronary and aortic calcification, a marker of atherosclerosis, measured 8 years after menopause, 11 years later in these women.     

Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women

Background

Higher androgen and lower estrogen levels are associated with cardiovascular disease (CVD) risk factors in women. However, studies on sex hormones and incident CVD events in women have yielded conflicting results.

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.     

Plasma fasting and nonfasting triglycerides and high-density lipoprotein cholesterol in atherosclerotic stroke: Different profiles according to low-density lipoprotein cholesterol

Although low-density lipoprotein cholesterol (LDL-C) is the main lipid target for cardiovascular risk reduction, recent studies suggest that other lipid indicies are also associated with vascular events. We hypothesized that the association of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) with atherosclerotic stroke (AS) differs depending on LDL-C levels. Data prospectively collected on subjects admitted with acute ischemic stroke to a university medical center were analyzed. We divided the patients into AS and non-atherosclerotic stroke (NAS) groups and independent association of lipid parameters and genetic influences of apolipoprotein A5 (ApoA5) polymorphisms with AS were evaluated. Of 268 patients, 160 (59.7%) were classified with AS and 108 (40.3%) were classified with NAS. Vascular risk factors were more prevalent in AS patients than in those with NAS; additionally, AS patients' anthropometric indexes and laboratory findings showed that they were prone to atherosclerosis. AS was independently associated with fasting TG (OR per 10 mg/dL increase, 1.38; 95% CI, 1.16–1.64; OR for highest vs. lowest tertile, 12.85; 95% CI, 3.31–49.85), HDL-C (OR per 10 mg/dL increase, 0.61; 95% CI, 0.42–0.88; OR for lowest vs. highest tertile, 4.28; 95% CI, 1.16–15.86), and nonfasting TG (OR per 10 10 mg/dL increase, 1.25; 95% CI, 1.11–1.42; OR for highest vs. lowest tertile, 8.20; 95% CI, 1.98–33.88) only among patients with LDL <100 mg/dL. No interaction was observed between fasting and nonfasting TG and ApoA5 polymorphisms. In conclusion, fasting and nonfasting TG and HDL-C were associated with AS only when patients had low levels of LDL-C. Non-LDL-C may have an additional role in addition to the LDL-C levels in AS development.     

Thyroid hormone use, hyperthyroidism and mortality in older women

Purpose

Thyroid dysfunction is common, particularly among older women. The safety of thyroid hormone use and long-term prognosis of hyperthyroidism remain controversial. We performed a prospective cohort study to examine the relationship among thyroid hormone use, previous hyperthyroidism, abnormal thyroid function, and mortality.

Methods

We studied 9449 community-dwelling white women aged ≥65 years followed for 12 years. For analyses of thyroid function, we performed a nested case-cohort in 487 women using a third-generation thyroid-stimulating hormone assay. Causes of death were adjudicated based on death certificates and hospital records.

Results

Twelve percent of the 9449 women took thyroid hormone at baseline, and the mean duration of thyroid hormone use was 15.8 years; 9.4% of participants reported a history of hyperthyroidism. During 12 years of follow-up, 3159 women died (33%). In multivariate analysis, mortality among users of thyroid hormone was similar to that observed for nonusers (relative hazard [RH] 1.11, 95% confidence interval [CI], 0.98-1.24, P = .09). Previous hyperthyroidism was associated with a higher risk of all-cause mortality (RH 1.20, 95% CI, 1.06-1.36), particularly cardiovascular mortality (RH 1.46, 95% CI, 1.20-1.77). Low (≤0.5 mU/L) or high (>5 mU/L) thyroid-stimulating hormone levels were not associated with excess total or cause-specific mortality, but the power to detect these relationships was limited.

Conclusions

Among older women, thyroid hormone use is not associated significantly with excess mortality, but previous hyperthyroidism may be associated with a small increase in all-cause and cardiovascular mortality. Additional long-term studies of hyperthyroidism and its treatment should further explore these findings.     

Study Design, Rationale, and Baseline Characteristics: Evaluation of Fenofibric Acid on Carotid Intima-Media Thickness in Patients with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy (FIRST) Trial

Purpose

Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels contribute to cardiovascular disease risk and can be effectively treated with fenofibric acid. A trial is under way to evaluate the effect of once-daily fenofibric acid or placebo on carotid intima-media thickness (CIMT) progression in patients with controlled low-density lipoprotein cholesterol (LDL-C) levels achieved through atorvastatin treatment, but with high TG and low HDL-C levels.

Methods

In this multicenter, double-blind study, 682 patients were randomized to once-daily delayed-release capsules of choline fenofibrate 135?mg (fenofibric acid [Trilipix?; Abbott, North Chicago, IL]) or placebo plus atorvastatin treatment after a 2- to 10-week diet and atorvastatin run-in period. Key inclusion criteria included age ≥45?years; posterior-wall common CIMT ≥0.7?mm on at least one side at baseline; fasting results of TG ≥150?mg/dL, and HDL-C ≤45?mg/dL for men or HDL-C ≤55?mg/dL for women at screening while receiving atorvastatin; controlled LDL-C; and known coronary heart disease (CHD) or a CHD risk equivalent. The primary efficacy variable is the rate of change from baseline through week 104 in the mean posterior-wall intima-media thickness of the common carotid arteries (composite value of left and right sides).

Conclusions

This trial is the first to examine the effect of fenofibric acid on CIMT and the first CIMT trial to select patients with controlled LDL-C and elevated TG and low HDL-C as inclusion criteria. Also, this trial will prospectively evaluate the effect of treatment on LDL particles and address shortcomings of previous CIMT trials.     

Clinical significance of high-density lipoprotein cholesterol in patients with low low-density lipoprotein cholesterol.

OBJECTIVES: We sought to evaluate the significance of high-density lipoprotein cholesterol (HDL-C) in the context of low low-density lipoprotein cholesterol (LDL-C). BACKGROUND: Earlier studies support an inverse correlation between circulating HDL-C and coronary risk in patients with normal or elevated LDL-C. METHODS: This study involved 4,188 patients attending the Palo Alto Veterans Administration Medical Center or affiliated clinics with LDL-C levels below 60 mg/dl. Outcomes were examined 1 year after the index LDL-C date. The combined primary end point was myocardial injury or hospitalization from ischemic heart disease. The secondary end point was all-cause mortality. RESULTS: Mean HDL-C levels (mg/dl) by quartile (Q) were: Q1 28 mg/dl, Q2 36 mg/dl, Q3 43 mg/dl, and Q4 63 mg/dl. The rate of myocardial injury or hospitalization for ischemic heart disease showed an inverse relationship to HDL-C (adjusted odds ratios: Q1 1.59 [95% confidence interval (CI) 1.16 to 2.19], Q2 1.39 [95% CI 1.01 to 1.92], Q3 1.33 [95% CI 0.96 to 1.84], and Q4 reference) that persisted regardless of statin use or recent myocardial injury. Analyzing HDL-C as a continuous variable revealed a 10% [95% CI 3% to 17%] increase in the combined end point of myocardial injury or hospitalization for ischemic heart disease for every 10-mg/dl decrease in HDL-C. The unadjusted and adjusted incidence of all-cause mortality demonstrated a U-shaped relationship to HDL-C (adjusted odds ratios: Q1 1.13 [95% CI 0.79 to 1.62], Q2 0.97 [95% CI 0.67 to 1.40], Q3 0.74 [95% CI 0.50 to 1.09], and Q4 reference). CONCLUSIONS: The inverse relationship between HDL-C and coronary risk persists even among patients with LDL-C below 60 mg/dl, although a U-shaped relationship is observed between HDL-C and all-cause mortality.     

Lifestyle determinants of high-density lipoprotein cholesterol: the National Heart, Lung, and Blood Institute Family Heart Study

Background

While genetic factors are major determinants of high-density lipoprotein cholesterol (HDL-C), environmental factors also play a role. The latter include 3 modifiable lifestyle factors: alcohol consumption, physical activity, and smoking.

Methods

We compared the relative effects of alcohol, physical activity, and smoking on HDL-C levels, using data from 2309 subjects (1226 women and 1083 men), aged 25 to 91 years, from randomly selected families participating in the National Heart, Lung, and Blood Institute Family Heart Study.

Results

Alcohol consumption was associated with the largest increment in HDL-C (an increase of 9.0-13.1 mg/dL from nondrinker to highest categories); physical activity with a more modest increment (an increase of 3.0-3.3 mg/dL from lowest to highest categories); and cigarette smoking with a large decrement in women (a decrease of 9.9 mg/dL) and a modest one in men (a decrease of 2.6 mg/dL) between nonsmoker and ≥20 cigarettes per day categories. The 3 lifestyle behaviors plus age, body mass index, education, and current estrogen use explained 22.4% and 18.2% of the total variance of HDL-C for women and men, respectively. Alcohol accounted for 28.6% of this variance among women and 50.1% among men; smoking accounted for 6.7% and 3.3%, respectively, and physical activity for 2.7% and 3.6%, respectively, among women and men. Age, body mass index, education, and current estrogen use explained the remaining 62.0% and 43.0%, respectively, of the variance attributed to environmental factors.

Conclusions

This study suggests that, among lifestyle behaviors, alcohol consumption is the more important correlate of HDL-cholesterol.     

Risk of recurrent coronary events in relation to use and recent initiation of postmenopausal hormone therapy

BACKGROUND: The finding from the Heart and Estrogen/Progestin Replacement Study (HERS) of increased coronary risk restricted to the first year after starting postmenopausal hormone therapy raises new questions about the role of hormone therapy in women with coronary heart disease. We assessed the risk of recurrent myocardial infarction or coronary heart disease death associated with the use and recent initiation of hormone therapy in women who survived a first myocardial infarction. METHODS: The setting for this population-based inception cohort study was Group Health Cooperative, a health maintenance organization. We studied 981 postmenopausal women who survived to hospital discharge after their first myocardial infarction between July 1, 1986, and December 31, 1996. We obtained information on hormone use from the Group Health Cooperative computerized pharmacy database and identified recurrent coronary events by medical record review. RESULTS: During median follow-up of 3.5 years, there were 186 recurrent coronary events. There was no difference in the risk of recurrent coronary events between current users of hormone therapy and other women (adjusted relative hazard [RH], 0.96; 95% confidence interval [CI], 0.62-1.50). Relative to the risk in women not currently using hormones, there was a suggestion of increased risk during the first 60 days after starting hormone therapy (RH, 2.16; 95% CI, 0.94-4.95) and reduced risk with current hormone use for longer than 1 year (RH, 0.76; 95% CI, 0.42-1.36). CONCLUSION: These results are consistent with the findings from the HERS, suggesting a transitory increase in coronary risk after starting hormone therapy in women with established coronary heart disease and a decreased risk thereafter.     

Lipoprotein (a) and coronary heart disease among women: beyond a cholesterol carrier?

AIMS: With its homology with plasminogen, lipoprotein(a) [Lp(a)] may be related to thrombosis and inflammation. We assessed the role of Lp(a) in coronary heart diseases (CHD) by a recently developed assay that is not affected by the plasminogen-like Kringle-type-2 repeats. METHODS AND RESULTS: Of 32 826 women from the Nurses' Health Study, who provided blood at baseline, we documented 228 CHD events during 8 years of follow-up. Each case was compared with two matched controls. In a multivariable model adjusted for body mass index, family history, hypertension, diabetes, post-menopausal hormone use, physical activity, blood drawing characteristics, and alcohol intake, the odd ratio (OR) for Lp(a) levels > or =30 mg/dL was 1.9(95% CI: 1.3-3.0) when compared with those with Lp(a)<30 mg/dL. Women with high levels of both Lp(a) (> or =30 mg/dL) and fibrinogen (> or =400 mg/dL) had an OR of 3.2(95% CI: 1.6-6.5) for CHD, when compared with the combination of low levels (P interaction=0.05). Women with high levels of both Lp(a) and C-reactive protein (> or =3 mg/L) had an OR of 3.67(95% CI: 2.03-6.64) for CHD, when compared with the combination of low levels (P interaction=0.06). CONCLUSION: Lp(a) levels >30 mg/dL are associated with twice the risk of CHD events among women and may be related to thrombosis and inflammation.     

Associations between low-density lipoprotein cholesterol and haemorrhagic stroke

OBJECTIVETo investigate the associations between the blood concentrations of low-density lipoprotein cholesterol (LDL-C) and the clinical features of haemorrhagic stroke.METHODSThis study analysed the data from patients with acute haemorrhagic stroke at a comprehensive stroke centre from 2013 to 2018. Patients were stratified into three groups according to their baseline LDL-C levels: < 70, 70 to < 100 and ≥ 100 mg/dL. We used multivariate logistic regression models to analyse the associations between LDL-C and the risks of having severe neurological deficits (National Institute Health Stroke Scale [NIHSS] scores ≥ 15) and unfavourable outcomes (modified Rankin Scale [mRS] scores>2) at discharge.RESULTSSix-hundred and six patients were analysed. Their median age was 58 years. Among the patients, 75 (12%) patients had LDL-C levels < 70 mg/dL, 194 (32%) patients had LDL-C levels between 70 to < 100 mg/dL and the other 337 (56%) patients had LDL-C levels ≥ 100 mg/dL. Patients with higher LDL-C levels were less likely to suffer severe neurological deficits (LDL-C: 70 to < 100 vs. < 70 mg/dL, adjusted odds ratio [OR]: 0.29, 95% CI: 0.15–0.57; LDL-C: ≥ 100 vs. < 70 mg/dL, adjusted OR = 0.27, 95% CI: 0.15–0.51) and to have unfavourable outcomes at discharge (LDL-C: 70 to < 100 vs. < 70 mg/dL, adjusted OR = 0.50, 95% CI: 0.29–0.87 and LDL-C: ≥ 100 vs. < 70 mg/dL, adjusted OR = 0.46, 95% CI: 0.28–0.78). CONCLUSIONSAn LDL-C level < 70 mg/dL was independently associated with severe neurological deficits of haemorrhagic stroke and may increase the risks of unfavourable outcomes at discharge.

Hyperlipidaemia, especially increased levels of low-density lipoprotein cholesterol (LDL-C), is an independent risk factor for acute ischaemic stroke (AIS).^{[1, 2]} In a cohort study with 27,937 healthy women, subjects with LDL-C ≥ 151 mg/dL had a hazard ratio (HR) of 1.85 to experience an AIS within 11 years relative to those with an LDL-C < 96 mg/dL, where the 95% confidence interval (CI) was 1.22 to 2.80. ^[3]Lipid-lowering therapy is one of the critical strategies for both primary and secondary prevention of AIS.^[4,5] A meta-analysis of the AIS prevention studies indicated that lipid-lowering therapy was associated with lower risks of AIS in the primary (risk ratio (RR): 0.70, 95% CI: 0.60–0.82; P < 0.001) and the secondary (RR: 0.80, 95% CI: 0.70-0.90; P < 0.001) prevention settings. ^[6] Additionally, a meta-analysis in the setting of atherosclerosis coronary heart disease (CHD) also showed that with every 39 mg/dL decrease in the LDL-C levels, the risks of major adverse cardiovascular events (including CHD death, nonfatal myocardial infarction, AIS or unstable angina requiring hospitalization) appeared to be 24% lower (adjusted HR = 0.76, 95% CI: 0.63–0.91; P = 0.0025).^[7] Our prior study found that achieving an LDL-C < 70 mg/dL may be effective in inhibiting the progression of carotid atherosclerosis plaques in patients with AIS. ^[8]However, lower LDL-C levels might increase the risks of intracranial haemorrhage (ICH). LDL-C < 90 mg/dL was associated with a higher risk of haemorrhage transformation after AIS, which was attributable to large artery atherothrombosis: the risks were increased by 54.0% with each 39 mg/dL decrease in the LDL-C levels (adjusted odds ratio (OR): 0.46 per 39 mg/dL increase, 95% CI: 0.22–0.98). ^[9] A case-control study found the LDL-C level was significantly lower in patients with ICH compared to the controls (114 vs. 128 mg/dL; P = 0.016).^[10] A post hoc analysis of the SPARCL study also found that patients with LDL-C < 70 mg/dL had a trend of increased risks of ICH relative to those with LDL-C ≥ 100 mg/dL (HR = 1.28, 95% CI: 0.78–2.09). ^[11] Above all, the target value of LDL-C to be achieved through lipid-lowering therapy is still unclear due to the potential risks of ICH. We carried out a single-centre retrospective cohort study to investigate the associations between the LDL-C levels (< 70, 70 to < 100 and ≥ 100 mg/dL) and the outcomes of haemorrhagic stroke to provide preliminary information about safe targets for lipid-lowering therapy.     

The effect of estrogen plus progestin on knee symptoms and related disability in postmenopausal women: The heart and estrogen/progestin replacement study,a randomized,double‐blind,placebo‐controlled trial

Objective

Most observational studies suggest that postmenopausal women taking hormone replacement therapy have a reduced risk of radiographic knee and hip osteoarthritis (OA). There are no randomized trial data on the association of hormone treatment with knee or hip OA, and no studies have been published regarding the relationship of hormone treatment to knee or hip symptoms. This study examined the association of hormone treatment with prevalent knee symptoms and disability related to knee pain as assessed at the final visit of the Heart and Estrogen/Progestin Replacement Study (HERS).

Methods

The HERS was a 4‐year randomized, double‐blind, placebo‐controlled trial of estrogen plus medroxy progesterone acetate for prevention of coronary heart disease in postmenopausal women with documented coronary disease. Participants in this substudy on knee pain were 969 postmenopausal women, with a mean age of 66 years and mean body mass index of 28.6 kg/m², attending the final visit at 9 clinical centers. Frequent knee symptoms were assessed by interview and the severity of knee pain and disability related to knee pain were determined using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Knee symptoms and disability were compared between women assigned to receive hormones and those assigned to receive placebo.

Results

Frequent knee pain was reported in 24.1% of women assigned to receive hormone therapy versus 26.1% of those assigned to the placebo group, a difference of −2.0% (95% confidence interval [95% CI] −7.4% to 3.5%). Among women with knee pain, there were no differences in the severity of pain (score difference −0.2, 95% CI −1.2 to 0.8) or disability (score difference −0.7, 95% CI −3.8 to 2.4) as assessed on the WOMAC. All results were similar for women whose body mass index was either above or below the median.

Conclusion

In a group of older, postmenopausal women with cardiac disease, we found no significant effect of 4 years of estrogen plus progestin therapy compared with placebo on knee pain and related disability. Our findings may not apply to other groups of women or to the effect of hormone therapy on the structural changes of knee OA.