Search

Objective: To evaluate lipids and apolipoproteins as predictors of cardiovascular mortality and morbidity (CVD) in patients with spondyloarthritis (SpA)., Methods: In the pooled cohort of participants in the IDEAL, TNT, and CARDS trials, 50 had ankylosing spondylitis (AS), 36 had psoriatic arthritis (PsA), and 21,641 did not have AS or PsA (non-SpA). We compared lipid levels at baseline between AS or PsA and non-SpA, and hazard ratios (HR) for CVD were calculated in a Cox proportional hazard model., Results: Atherogenic lipids were lower in samples from AS, but not in PsA, compared to non-SpA. The HR for 1 SD increase in baseline lipids for future CVD was for total cholesterol 1.39 (95% CI 0.82, 2.36) in AS, 1.01 (95% CI 0.44, 2.31) in PsA, and 1.10 (95% CI 1.07, 1.14) in non-SpA. Both high-density lipoprotein (HDL) and apolipoprotein (ApoA-1) were significantly associated with CVD in AS (HR 3.67, 95% CI 1.47, 9.06, and HR 1.89, 95% CI 1.02, 3.54, respectively), in contrast to PsA (HDL: HR 1.03, 95% CI 0.49, 2.15; ApoA-1: HR 0.79, 95% CI 0.34, 1.89) and non-SpA (HDL: HR 0.86, 95% CI 0.84, 0.89; ApoA-1: HR 0.88, 95% CI 0.85, 0.91)., Conclusion: HDL and ApoA-1 were surprisingly associated with increased risk of future CVD in patients with AS, whereas these lipids were protective in non-SpA.

Objective: To examine the relationship of estrogen-induced changes in lipids and lipoproteins with alterations in the coagulation system., Methods: Coagulation and lipid indices were measured in 31 postmenopausal women, ages 40-60 years, after a 3-month course of 0.625-mg conjugated equine estrogen. We analyzed changes in variables from baseline to 3 months using t tests for paired samples or the Wilcoxon matched-pairs signed-rank test., Results: Unopposed estrogen replacement therapy produced statistically significant decreases in antithrombin-III antigen (P = .006) and activity (P = .001) and total protein S (P = .003) and a significant increase in protein C antigen (P = .017). C4b-binding protein also decreased significantly from baseline to 3 months (P < .001). Mean fibrinogen level decreased by 18.2 mg/dL, not a statistically significant change (P = .213). Estrogen produced the expected statistically significant changes in lipids and lipoproteins. Several correlations between changes in lipids and lipoproteins and coagulation indices were statistically significant. Protein C antigen and activity changes correlated directly with high-density lipoprotein cholesterol changes (r = .52, P < or = .005; r = .38, P < or = .05; respectively), and protein C antigen also correlated directly with increases in apoprotein A-I (r = .54, P < or = .005). Triglyceride changes correlated directly with changes in protein C antigen (r = .36, P < or = .05) and activity (r = .49, P < or = .005) and inversely with C4b-binding protein (r = -.58, P < or = .01). Apoprotein B was correlated with free protein S (r = .48, P < or = .01)., Conclusions: Although several estrogen-induced changes may decrease atherosclerotic potential and hypercoagulability, others may promote coagulability. These divergent effects may be manipulated pharmacologically by other estrogen compounds or by the addition of various progestins.

Estrogen has favorable effects on lipid and lipoprotein coronary risk factors when given orally. These effects are less evident when estrogen is given in non-oral forms. The effects of progestins and androgens are generally opposed to those of estrogen, although their effects on lipoprotein (a) [Lp(a)] do not follow this general rule. Estrogen-progestin and androgens have been shown to reduce Lp(a), but Lp(a) reduction is less when conjugated estrogens and medroxyprogesterone are combined than when estrogen is used alone. Overall, the effects of estrogens (both alone and in combination with progestin) on lipid levels and other coronary risk factors, are beneficial. Whether these effects translate into beneficial effects on clinical coronary disease is a question that awaits the outcome of clinical trials in progress.

Objective: To review the effects of exogenous estrogen and progestin on metabolic risk factors for coronary artery disease in women., Design: Review of selected literature., Setting: Population studies and clinical trials., Patients: Premenopausal and postmenopausal women., Interventions: Exogenous gonadal hormones in oral contraceptives and hormone replacement regimens., Main Outcome Measures: Lipoprotein, hemostatic, carbohydrate, and blood pressure metabolic parameters., Results: Favorable lipoprotein changes have been demonstrated in both observational studies and clinical trials of effects of exogenous hormones on cardiovascular risk factors in women. These include declines in low-density lipoprotein, apoprotein B, and lipoprotein(a), and increases in high-density lipoprotein (HDL), HDL2, and apoprotein A-I. Hormone replacement effects on triglyceride are minor and, in most patients, probably benign. Evidence is unconvincing that clinically significant changes in clotting factors, carbohydrate metabolism, or blood pressure take place as a result of postmenopausal hormone interventions. In fact, carbohydrate metabolism and blood pressure may be improved slightly. Metabolic studies do not, thus far, provide any contraindications to either estrogen replacement therapy (ERT) or hormone replacement therapy (HRT) in appropriately selected subjects. However, because studies of metabolic risk factors generally have been done in patients who were not hyperlipidemic, hypercoagulable, hyperglycemic, or hypertensive, little is known about the metabolic effects of ERT or HRT on pre-existing metabolic abnormalities.

Administration of conjugated equine estrogen to 31 postmenopausal women for 3 months produced 14.6% and 9.4% decreases in low density lipoprotein cholesterol (LDL-C) and apolipoprotein-B (apoB), and 11.5%, 12.7%, and 9.6% increases in high density lipoprotein cholesterol (HDL-C), apoA-I and apoA-II, respectively. Phospholipids of HDL2 and HDL3 were increased 57.9% and 19.3%, respectively, while relatively small increases in cholesterol of the two subfractions were not significant. Compositions of LDL and HDL and its subfractions were altered substantially with estrogen treatment. The proportion of LDL triglyceride to LDL-C was increased. The phospholipid content in both the HDL2 and HDL3 subfractions (compared to cholesterol) was increased significantly (34.8% and 10.7%, respectively), while the triglyceride content was increased only in the HDL2 subfraction (43.6%). Estrogen use also caused a 9.1% reduction in total apoE levels and a redistribution of apoE to the very low density lipoprotein (VLDL) from the LDL plus HDL fraction, resulting in a significant 19.5% decrease in apoE in the LDL plus HDL fraction. Changes in apoE in the VLDL fraction were associated positively with changes in the cholesterol levels of the VLDL fraction and inversely with changes in LDL-C and apoB levels, while changes in apoE in the LDL plus HDL fraction were associated positively with changes in the levels of HDL-C. Thus, estrogen causes alterations in lipoproteins that could potentially affect their metabolism and/or function.

Women, like men, are susceptible to coronary atherosclerosis. Like men, more women die of heart disease than all forms of cancer combined. Coronary atherosclerosis is the result of the interplay of a number of factors, the most important of which are abnormal levels of circulating lipoproteins. As more has become known about the mechanisms by which abnormal levels of circulating lipoproteins promote atherosclerosis, certain risk factors have emerged as concerns for women, including: (1) diabetes mellitus as a risk factor, perhaps through its more profound effects on circulating lipoproteins; (2) serum triglyceride levels, and (3) changes in high-density lipoprotein cholesterol. The widespread use of exogenous hormones in women as both oral contraceptives and postmenopausal hormone replacement may also play a role in developing atherosclerosis. In general, estrogen affects circulating lipoprotein levels favorably, whereas progestins have the opposite effect. The effects of estrogen/progestin combinations in either oral contraceptives or postmenopausal hormone replacement will depend on the relative dose and potency of each of these constituents. Epidemiologic studies indicate that the use of oral contraceptives has no profound effect on the long-term risk of heart disease, whereas unopposed estrogen (without progestin) in postmenopausal hormone replacement therapy may lower that risk considerably. Recent U.S. and European guidelines for the detection, evaluation, and treatment of hypercholesterolemia in adults make it imperative that obstetrician-gynecologists, in their dual role as primary-care physicians and prescribers of exogenous hormones, be aware of and informed about the relationship between circulating lipids and lipoproteins and coronary heart disease in women.

The effects of conjugated equine estrogen and subsequent cyclical progestogen supplementation on lipoprotein and apolipoprotein A-I levels were investigated in three groups of postmenopausal women. Unopposed conjugated equine estrogen (0.625 mg) lowered total cholesterol 4-8% and low-density lipoprotein (LDL) cholesterol 12-19% below pre-treatment levels in all three groups. Levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I were increased 9-13 and 9-18%, respectively, with unopposed estrogen. The increase in HDL cholesterol was mainly due to increases in the high-density lipoprotein2 (HDL2) subfraction. Addition of medroxyprogesterone acetate, norethindrone acetate, or d,l-norgestrel at doses shown previously to provide protection against endometrial hyperplasia reversed some of the beneficial estrogen effects, reducing levels of HDL cholesterol 14-17%, HDL2 cholesterol 22-37%, and apolipoprotein A-I 11-15% from those obtained with unopposed estrogen. The LDL cholesterol levels fell 12-19% with unopposed estrogen but remained 7-12% below baseline when progestogens were added. These observations demonstrate that after 3 months of treatment, all three progestogens reversed some of the favorable effects of unopposed estrogen on lipoproteins but permitted a continued modest reduction in LDL cholesterol.

Atherosclerosis, lipoprotein structure, lipoprotein metabolism and role in atherogenesis, epidemiology of lipoproteins and coronary artery disease, and current public health guidelines for cholesterol control are described. Low density lipoprotein cholesterol levels rise with age in both men and women. High density lipoprotein (HDL) levels decline after menopause. Special aspects of coronary risk in women include the stronger role of diabetes, hypertriglyceridemia and HDL. In addition, the effects of exogenous hormone therapy, both in the form or oral contraceptives and post menopausal hormone replacement should be considered. Careful attention to these issues may reduce cardiovascular morbidity in adult women.

Twenty-four obese but otherwise normal men and women were followed for: Two weeks on their usual food intake; eight weeks on a high-protein, low-carbohydrate diet; and then again for two weeks on their usual diet. During this time, several metabolic parameters were measured bimonthly. The high-protein, low-carbohydrate dieting resulted in substantial weight loss, probably due to a combination of salt and water loss, as well as caloric restriction. Plasma triglycerides fell as well. Significant increases occurred in LDL-cholesterol, uric acid, and free fatty acid levels. HDL-cholesterol levels failed to rise despite significant weight loss, indicating that the previously reported relationship between HDL-cholesterol and weight may be dependent, in part, on the composition of the diet.

Recent studies suggest that apolipoproteins and subfractions of high-density lipoprotein (HDL) cholesterol may be better predictors of atherosclerotic coronary artery disease (CAD) than are plasma cholesterol and total HDL cholesterol. To examine this hypothesis, plasma cholesterol and triglyceride, cholesterol of low-density lipoprotein, HDL and its subfractions 2 and 3, apolipoprotein A-I, the apolipoprotein B of low-density lipoprotein, the ratio of apolipoprotein EII to EIII, and ratios of several of these variables were measured in a selected series of 126 patients (83 men and 43 women) who underwent coronary angiography for suspected CAD. Mean values of many of these variables differed significantly between the men with CAD and the men without significant CAD, when controlled for age, use of beta blockers and diuretic drugs. Using multivariate logistic regression analysis, the only variable that made a significant independent contribution in predicting CAD in men was the ratio of HDL cholesterol to total plasma cholesterol (p less than 0.0001). The mean of this ratio was 0.17 +/- 0.01 mg/dl in the men with CAD and 0.23 +/- 0.02 mg/dl in the male controls. All men with ratios of less than 0.15 mg/dl had significant CAD, defined as 50% or greater luminal diameter narrowing of 1 or more of the major coronary arteries. No measurement was a significant univariate or multivariate predictor of CAD in the women, but the power to detect such predictors was reduced because of small group sizes. In conclusion, the ratio of HDL cholesterol to plasma cholesterol may be superior to many of the more recently described lipoprotein and apolipoprotein-derived predictors of CAD.

We investigated the association of plasma high-density lipoprotein (HDL) cholesterol levels with levels of cholesterol in other plasma lipoprotein fractions (low-density [LDL], very low density [VLDL] and their sum) and with total plasma cholesterol and triglyceride levels in 3493 males and 3318 females in the Lipid Research Clinics (LRC) Prevalence Study. Correlation coefficients were calculated for each stratum of age, sex and hormone use using a logarithmic transformation. The correlations of log HDL cholesterol with the other lipid and lipoprotein fractions generally depended strongly on age and sex but not on use of gonadal hormones. In the 20-70-year range, the age dependence of each correlation coefficient was well described by a linear regression model. The weakly positive association between HDL and total cholesterol levels in adults and the marked negative association of HDL cholesterol with triglyceride and VLDL cholesterol levels in almost all strata are in good general agreement with the results of earlier studies.

Atherosclerotic risk factors in cardiovascular disease include several that may be modified by changes in life-style or with drugs. Oral contraceptive agents may affect lipoproteins and glucose tolerance in particular. This paper reviews the relationship between lipoproteins, abnormal glucose tolerance and atherosclerosis and the implications that these relationships have for all oral contraceptive users.

As part of the National Exercise and Heart Disease Project, 223 postcoronary men, aged 30 to 64, were randomly assigned to moderate exercise or control groups. Levels of total plasma cholesterol, high- and low-density lipoprotein (HDL and LDL) cholesterol, and triglycerides were measured. At baseline, alcohol intake, weight, and skin-fold thickness but not treadmill work capacity correlated with triglyceride or HDL cholesterol levels. After one year, no clinically important change in lipid levels was observed in either group. Using multiple regression analysis of the combined groups, changes in several independent variables, including work capacity change, were not predictive of changes in lipid levels. Thus, changes in levels of fitness and/or regular exercise did not substantially influence HDL cholesterol or other lipid levels.

In order to determine the effects on plasma lipoproteins of oral contraceptives containing progestins with varying androgenic potency, 136 healthy women were randomized into 3 groups and followed prospectively for one year while receiving either 50 mcg ethinyl estradiol and 1.0 mg ethynodiol diacetate (EED), 50 mcg ethinyl estradiol and 1.0 mg norethindrone acetate (ENA), or 50 mcg ethinyl estradiol and 0.5 mg d-1 norgestrel (ENG). Comparison was made to a self-selected group of 50 women using alternative means of contraception. Plasma cholesterol increased by 7-9% and triglycerides by 32-57% in all 3 groups (p less than 0.05). ENG use resulted in other significant lipoprotein changes including an 18% increase in low density lipoprotein cholesterol (LDL-C), a 13% fall in high density lipoprotein cholesterol (HDL-C) and a 27% decline in HDL2 cholesterol (HDL2-C) (p less than 0.05). Apoprotein A-I (Apo A-I) increased by 9% with ENA and by 11% with EED (p less than 0.05), but did not change significantly with ENG. This prospective study demonstrates that in oral contraceptive agents with identical estrogen, progestins with different androgenic potency produce major and different changes in plasma lipoproteins.