Risk Markers In Women Research Articles

Cardiovascular risk markers during treatment with estradiol and trimegestone or dydrogesterone

Objective To study cardiovascular risk markers in women taking estradiol/trimegestone or estradiol/dydrogesterone. Design Multicenter, randomized, prospective, double-blind study of 184 healthy post-menopausal women randomized to 6 cycles of either estradiol (2 mg) + trimegestone (0.5 mg) (T-group) or estradiol (2 mg) + dydrogesterone (10 mg) (DYDR group). Cardiovascular risk markers were measured before, after cycle 1, 3 and 6 and at 4 weeks post-treatment. Results Fibrinogen was reduced in both groups but more markedly in the DYDR group. Factor VIIc activity levels decreased in both groups with a greater change in the T-group. Factor VII antigen was increased in both groups with a greater increase in the DYDR group. Factor VIIa was increased in the DYDR group only. Plasminogen levels were also increased in both groups with a greater increase in the T-group. There were no statistically significant changes in lipid variables between the different regimens. Changes in total cholesterol and LDL cholesterol were correlated positively with changes in factor VIIc in the DYDR group and negatively with changes in factor VIIc in the T-group. Trigemestone was associated with a better bleeding pattern. Conclusions Trimegestone was associated with less procoagulant changes in factor VIIa and factor VIIc activity and larger decrease in PAI-1 activity compared with the dydrogesterone preparation. These results reflect less androgenic properties of the trimegestone preparation. The fibrinogen level and Lp(a) were more decreased during dydrogesterone treatment. Further investigation is required to clarify the relative importance of beneficial effects with respect to cardiovascular risk.

A history of preeclampsia identifies women who have underlying cardiovascular risk factors

The objective of this study was to prospectively assess physical and biochemical cardiovascular risk markers in women who had developed preeclampsia (PE) at 1 year postpartum. Following an overnight fast, previously PE (n = 70) and normotensive women (n = 70) had weight and blood pressure recorded and levels of morning blood for insulin, glucose, C-reactive protein, lipids, cholesterol, and urine for microalbumin and creatinine measured. Body mass index, homeostatic model assessment index, and incidence of metabolic syndrome were determined. At 1 year postpartum, markers of cardiovascular disease were different between the groups. There were also differences in the number of women with abnormal values. Mathematical modeling of cardiovascular event risk suggests that PE increases the risk by 2- to 3-fold; the risk was greatest for women with severe PE. The development of PE is 1 of the earliest clinically identifiable markers of a woman's heightened risk of cardiovascular disease.

Growth Hormone Deficiency by Growth Hormone Releasing Hormone-Arginine Testing Criteria Predicts Increased Cardiovascular Risk Markers in Normal Young Overweight and Obese Women

Little is known about the relationship between GH and cardiovascular risk markers in women without organic hypothalamic/pituitary disease. The objective of the study was to determine whether healthy young overweight and obese women, who would be classified as having GH deficiency (GHD) based on standard criteria used in hypopituitarism (peak GH after stimulation with GHRH and arginine < 5 ng/ml), have increased cardiovascular risk markers. This was a cross-sectional study. The study was conducted at the General Clinical Research Center. Forty-five women of reproductive age, mean age 33.1 +/- 1.2 yr and mean body mass index (BMI) 30.9 +/- 1.0 kg/m(2). There was no intervention. Measures included carotid intima-medial thickness, high-sensitivity C-reactive protein (hsCRP), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein, triglycerides, E-selectin, soluble intercellular adhesion molecule-1, TNF-alpha receptor I, TNF-alpha receptor II, fasting insulin levels, and oral glucose tolerance testing. Twenty-six percent of overweight or obese subjects and none with BMI less than 25 kg/m(2) met criteria for GHD. Subjects who met GHD criteria had a mean BMI of 37.0 +/- 1.7 kg/m(2) (range 28.6-43.6 kg/m(2)), and their mean waist circumference (110.1 +/- 3.5 cm) was higher than in overweight/obese women with GH sufficiency (P = 0.007). Mean carotid intima-media thickness, hsCRP, soluble intercellular adhesion molecule-1, TNF-alpha receptor I, and TNF-alpha receptor II levels were higher, and HDL lower, in women meeting GHD criteria than in GH sufficiency. Differences in HDL, hsCRP, and TNF-alpha receptor II remained after controlling for age plus BMI, waist circumference, or trunk fat. There were no differences in measures of insulin resistance. There may be a relative GHD syndrome in overweight and obese women without organic pituitary or hypothalamic disease that confers increased cardiovascular risk, independent of weight.

Growth Hormone Decreases Visceral Fat and Improves Cardiovascular Risk Markers in Women with Hypopituitarism: A Randomized, Placebo-Controlled Study

Data regarding gender-specific efficacy of GH on critical endpoints are lacking. There are no randomized, placebo-controlled studies of physiological GH therapy solely in women. Our objective was to determine the effects of physiological GH replacement on cardiovascular risk markers and body composition in women with GH deficiency (GHD). This was a 6-month, randomized, placebo-controlled, double-blind study. The study was conducted at the General Clinical Research Center. 43 women with GHD due to hypopituitarism were included in the study. Study participants were randomized to receive GH (goal mid-normal serum IGF-1) or placebo. Cardiovascular risk markers, including high-sensitivity C-reactive protein, tissue plasminogen activator, and body composition, including visceral adipose tissue by cross-sectional computed tomography, were measured. Mean daily GH dose was 0.67 mg. The mean IGF-1 sd score increased from -2.5 +/- 0.3 to -1.4 +/- 0.9 (GH) (P < 0.0001 vs. placebo). High-sensitivity C-reactive protein decreased by 38.2 +/- 9.6% (GH) vs.18.2 +/- 6.0% (placebo) (P = 0.03). Tissue plasminogen activator and total cholesterol decreased, and high-density lipoprotein increased. Homeostasis model assessment-insulin resistance and other markers were unchanged. Body fat decreased [-5.1 +/- 2.0 (GH) vs. 1.9 +/- 1.0% (placebo); P = 0.002] as did visceral adipose tissue [-9.0 +/- 5.9 (GH) vs. 4.3 +/- 2.7% (placebo); P = 0.03]. Change in IGF-1 level was inversely associated with percent change in visceral adipose tissue (r = -0.61; P = 0.002), total body fat (r = -0.69; P < 0.0001), and high-sensitivity C-reactive protein (r = -0.51; P = 0.003). Low-dose GH replacement in women with GHD decreased total and visceral adipose tissue and improved cardiovascular markers, with a relatively modest increase in IGF-1 levels and without worsening insulin resistance.

Growth Hormone Decreases Visceral Fat and Improves Cardiovascular Risk Markers in Women with Hypopituitarism: A Randomized, Placebo-Controlled Study

Growth Hormone Decreases Visceral Fat and Improves Cardiovascular Risk Markers in Women with Hypopituitarism: A Randomized, Placebo-Controlled Study

Growth Hormone Decreases Visceral Fat and Improves Cardiovascular Risk Markers in Women with Hypopituitarism: A Randomized, Placebo-Controlled Study

Growth Hormone Decreases Visceral Fat and Improves Cardiovascular Risk Markers in Women with Hypopituitarism: A Randomized, Placebo-Controlled Study

Lipoprotein(a), Measured With an Assay Independent of Apolipoprotein(a) Isoform Size, and Risk of Future Cardiovascular Events Among Initially Healthy Women

Controversy exists as to whether lipoprotein(a), a lipoprotein with homology to plasminogen, is a clinically meaningful cardiovascular risk marker in women. There is also poor agreement among lipoprotein(a) levels obtained by different assays. To determine the association of lipoprotein(a) levels, measured with an assay independent of apolipoprotein(a) isoform size, with the incidence of future cardiovascular events. Prospective study of 27,791 initially healthy women in the Women's Health Study, enrolled between November 1992 and July 1995 and followed up for 10 years. Lipoprotein(a) level was measured in blood samples obtained at baseline with an assay independent of apolipoprotein(a) isoform size. Hazard ratios (HRs) for first-ever major cardiovascular events (nonfatal myocardial infarction, nonfatal cerebrovascular event, coronary revascularization, or cardiovascular deaths). During follow-up, there were 899 incident cardiovascular events. After adjusting for age, smoking, blood pressure, body mass index, total cholesterol, high-density lipoprotein cholesterol, diabetes, hormone use, C-reactive protein, and randomization treatment groups, women in the highest quintile of lipoprotein(a) (> or =44.0 mg/dL) were 1.47 times more likely (95% CI, 1.21-1.79; P for trend <.001) to develop cardiovascular events than women in the lowest quintile (< or =3.4 mg/dL). This association, however, was due almost entirely to a threshold effect among those with the highest lipoprotein(a) levels. After adjusting for all of the variables listed above, the HR associated with lipoprotein(a) levels exceeding the 90th percentile (> or =65.5 mg/dL) was 1.66 (95% CI, 1.38-1.99); 95th percentile (> or =83 mg/dL), 1.87 (95% CI, 1.50-2.34); and 99th percentile (> or =130.7 mg/dL), 1.99 (95% CI, 1.32-3.00), with almost no risk gradient at lower levels. Associations were strongest among women with low-density lipoprotein cholesterol (LDL-C) above the median level. In this subgroup, the adjusted HR associated with lipoprotein(a) levels exceeding the 90th percentile was 1.81 (95% CI, 1.48-2.23); 95th percentile, 1.93 (95% CI, 1.51-2.48); and 99th percentile, 1.93 (95% CI, 1.21-3.05) (P value for interaction with LDL-C = .001). In this cohort of initially healthy women, extremely high levels of lipoprotein(a) (> or =90th percentile), measured with an assay independent of apolipoprotein(a) isoform size, were associated with increased cardiovascular risk, particularly in women with high levels of LDL-C. However, the threshold and interaction effects observed do not support routine measurement of lipoprotein(a) for cardiovascular stratification in women.

Inflammatory cardiovascular risk markers in women with hypopituitarism.

Patients with hypopituitarism have increased cardiovascular mortality. A high prevalence of conventional cardiovascular risk factors, including obesity, central fat distribution, insulin resistance, and dyslipidemia, have been described in these patients. The inflammatory markers C-reactive protein (CRP) and IL-6 are predictors of cardiovascular events, and high levels of CRP have been reported in men with hypopituitarism and GH deficiency. However, little is known about inflammatory cardiovascular risk markers in women with hypopituitarism. We therefore investigated whether inflammatory and traditional cardiovascular risk markers are elevated in women with hypopituitarism. Fifty-three women with hypopituitarism and 111 healthy control women were included in this cross-sectional study. Morning blood samples were drawn after an overnight fast. Serum was assayed for CRP, IL-6, glucose, insulin, IGF-I, triglycerides, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein (HDL) cholesterol, lipoprotein(a), E2, total testosterone (total T) and free testosterone (free T), and dehydroepiandrosterone sulfate. IL-6 and CRP levels were higher in women with hypopituitarism than in healthy controls (P < 0.0001 for comparison between groups). In a multivariate model, CRP levels depended on hypopituitarism, body mass index (BMI), and estrogen use. There was an interaction between the effect of BMI and hypopituitarism on CRP levels, such that the importance of hypopituitarism in determining CRP levels disappeared at high BMIs. In a similar multivariate model, IL-6 levels depended on hypopituitarism and BMI. Total cholesterol, the total to HDL cholesterol ratio, and triglycerides were higher in hypopituitary patients, but only triglycerides and the total to HDL cholesterol ratio depended on hypopituitarism when controlling for BMI. There was no significant difference in lipoprotein(a) levels between hypopituitary women and control subjects. However, when controlling for estrogen use, lipoprotein(a) levels showed a trend toward being lower in the hypopituitary group (P = 0.075). In patients with hypopituitarism, CRP correlated negatively with IGF-I (r = -0.35; P = 0.010), total T (r = -0.42; P = 0.0020), and free T (r = -0.30; P = 0.031). Similarly, IL-6 correlated negatively with total T (r = -0.39; P = 0.0040) and androstenedione (r = -0.27; P = 0.048) in hypopituitary patients. In conclusion, hypopituitary women have increased levels of IL-6 and CRP, both of which are inflammatory markers of atherosclerosis. GH deficiency and androgen deficiency may contribute to these findings. Chronic inflammation may contribute to the high cardiovascular risk seen in this population.

Inflammatory Cardiovascular Risk Markers in Women with Hypopituitarism

Patients with hypopituitarism have increased cardiovascular mortality. A high prevalence of conventional cardiovascular risk factors, including obesity, central fat distribution, insulin resistance, and dyslipidemia, have been described in these patients. The inflammatory markers C-reactive protein (CRP) and IL-6 are predictors of cardiovascular events, and high levels of CRP have been reported in men with hypopituitarism and GH deficiency. However, little is known about inflammatory cardiovascular risk markers in women with hypopituitarism. We therefore investigated whether inflammatory and traditional cardiovascular risk markers are elevated in women with hypopituitarism. Fifty-three women with hypopituitarism and 111 healthy control women were included in this cross-sectional study. Morning blood samples were drawn after an overnight fast. Serum was assayed for CRP, IL-6, glucose, insulin, IGF-I, triglycerides, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein (HDL) cholesterol, lipoprotein(a), E2, total testosterone (total T) and free testosterone (free T), and dehydroepiandrosterone sulfate. IL-6 and CRP levels were higher in women with hypopituitarism than in healthy controls (P < 0.0001 for comparison between groups). In a multivariate model, CRP levels depended on hypopituitarism, body mass index (BMI), and estrogen use. There was an interaction between the effect of BMI and hypopituitarism on CRP levels, such that the importance of hypopituitarism in determining CRP levels disappeared at high BMIs. In a similar multivariate model, IL-6 levels depended on hypopituitarism and BMI. Total cholesterol, the total to HDL cholesterol ratio, and triglycerides were higher in hypopituitary patients, but only triglycerides and the total to HDL cholesterol ratio depended on hypopituitarism when controlling for BMI. There was no significant difference in lipoprotein(a) levels between hypopituitary women and control subjects. However, when controlling for estrogen use, lipoprotein(a) levels showed a trend toward being lower in the hypopituitary group (P = 0.075). In patients with hypopituitarism, CRP correlated negatively with IGF-I (r =− 0.35; P = 0.010), total T (r = −0.42; P = 0.0020), and free T (r = −0.30; P = 0.031). Similarly, IL-6 correlated negatively with total T (r = −0.39; P = 0.0040) and androstenedione (r = −0.27; P = 0.048) in hypopituitary patients. In conclusion, hypopituitary women have increased levels of IL-6 and CRP, both of which are inflammatory markers of atherosclerosis. GH deficiency and androgen deficiency may contribute to these findings. Chronic inflammation may contribute to the high cardiovascular risk seen in this population.

Hormone replacement therapy, inflammation, and hemostasis in elderly women.

Lipid-lowering by postmenopausal hormone therapy (HRT) explains only partly the assumed coronary risk reduction associated with therapy. To explore other possible mechanisms, we studied associations of HRT use with inflammation and hemostasis risk markers in women >/=65 years of age. Subjects were selected from 3393 participants in the fourth year examination of the Cardiovascular Health Study, an observational study of vascular disease risk factors. After excluding women with vascular disease, we compared levels of inflammation and hemostasis variables in the 230 women using unopposed estrogen and 60 using estrogen/progestin, with those of 196 nonusers selected as controls. Compared with nonusers, unopposed estrogen use was associated with 59% higher mean C-reactive protein (P<0.001), but with modestly lower levels of other inflammation indicators, fibrinogen, and alpha-1 acid glycoprotein (P<0.001). Factor VIIc was 16% higher among estrogen users (P<0.001), but this was not associated with higher thrombin production (prothrombin fragment 1-2), or increased fibrin breakdown (D-dimer). Concentration of plasminogen activator inhibitor-1 was 50% lower in both using groups (P<0.001) compared with nonusers, and this was associated with higher plasmin-antiplasmin complex: 8% higher in estrogen and 18% higher in estrogen/progestin users (P<0. 05). Relationships between the markers and hormone use were less pronounced in estrogen/progestin users, with no association for C-reactive protein except in women in upper 2 tertiles of body mass index (P for interaction, 0.02). The direction and strength of the associations of HRT use with inflammation markers differed depending on the protein, so it is not clear whether HRT confers coronary risk reduction through an inflammation-sensitive mechanism. Associations with hemostasis markers indicated no association with evidence of procoagulation and a possible association with increased fibrinolytic activity.

Coronary arteriographic findings in black patients and risk markers for coronary artery disease

Coronary arteriographic results are reported in 1535 black patients: 751 men (mean age 57 ± 11) and 784 women (mean age 59 ± 11). Among the black men 19%, 15%, 21%, and 4% had single-, double-, and triple-vessel and left main disease, respectively. Among the black women there were 12%, 10%, 15%, and 3% with similar involvement. Logistic regression models showed that most of the recognized risk factors were positively correlated with significant (at least one artery with ≥50% stenosis) coronary disease, but a history of hypertension was not a significant independent predictor in either sex. ECG evidence of previous infarction increased the odds of detecting significant coronary disease by the greatest amount when controlling for other significant risk markers in women. In men both previous infarction and atypical pain (negative) were equally important. This study confirms but does not explain previous reports that have revealed less than expected angiographic evidence of significant coronary artery disease in black compared with white persons.