The dual peroxisome proliferator-activated receptor alpha/gamma agonist tesaglitazar further improves the lipid profile in dyslipidemic subjects treated with atorvastatin

Tesaglitazar (GALIDA; AstraZeneca, Wilmington, DE) is a dual peroxisome proliferator-activated receptor alpha/gamma agonist previously in clinical development for the treatment of glucose and lipid abnormalities associated with type 2 diabetes mellitus and insulin resistance. This study compared the efficacy of tesaglitazar with that of pioglitazone as adjunctive therapy to atorvastatin in subjects with abdominal obesity and dyslipidemia. In this open-label, 3-way crossover study, 58 subjects received atorvastatin 10 mg once daily in a 6-week run-in period, followed by tesaglitazar 3 mg, pioglitazone 45 mg, or placebo, as adjunctive therapy to atorvastatin, in a randomized sequence for 6 weeks each. Serum triglycerides and other lipids, apolipoproteins, glucose, and insulin concentrations were compared between treatments. Tesaglitazar adjunctive therapy reduced serum triglycerides significantly more from baseline (-1.07 mmol/L) than pioglitazone (-0.33 mmol/L; P = .007) or placebo (-0.09 mmol/L; P < .0001). Tesaglitazar also resulted in significantly greater improvements in free fatty acids, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, low-density lipoprotein particle size, apolipoprotein (apo) B, apo C-III, and the apo B/apo A-I ratio compared with pioglitazone or placebo. Tesaglitazar adjunctive therapy also reduced fasting plasma glucose, fasting plasma insulin, and insulin resistance (homeostasis model assessment index) significantly more than pioglitazone or placebo (P < .0001 for all comparisons). Tesaglitazar was generally well tolerated in combination with atorvastatin, but hemoglobin and absolute neutrophil count decreased and serum creatinine increased more with tesaglitazar than with pioglitazone or placebo. These effects, also shown in previous trials, led to the discontinuation of the clinical development of the drug. In conclusion, the addition of tesaglitazar to a background of atorvastatin therapy further improved the dyslipidemia associated with insulin resistance.     

Gender differences in ambulatory blood pressure monitoring profile in obese, overweight and normal subjects

The incidence of obesity has increased enormously in the past several decades, and has been described as a modern epidemic. Obesity is a major factor contributing to hypertension. To the best of our knowledge, no study of ambulatory blood pressure monitoring (ABPM) comparing men with women in relation to body mass indexes (BMI) has been performed. From December 2002 to May 2006, we performed 24-h ABPM in 5950 subjects (3102 men and 2848 women), with a wide range of BMI (range 15.9-53.2 kg/m(2)). We defined obese subjects as those with BMI> or =30.0 kg/m(2), overweight subjects as those with BMI>25.0 and <30.0 kg/m(2), and normal subjects as those with BMI< or =25.0 kg/m(2). Data on 989 subjects (501 men and 488 women) aged from > or =18 to < or =69 years without antihypertensive treatment, atrial fibrillation or diabetes were included for analysis. We consistently found that obese men had the expected increased heart rate compared to normal and overweight men, whereas women (normal, overweight and obese) had similar HRs. In addition, normal and obese women had similar diastolic blood pressures (BP), as opposed to obese men, who had raised diastolic BP. These results may indicate that different pathogenetic mechanisms may be involved in the relationship between obesity and hypertension in men and women.     

Prothrombotic markers in asymptomatic dyslipidemic subjects

The aim of this study was to evaluate the plasma levels of prothrombotic markers—von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA)—in asymptomatic subjects with dyslipidemia. Asymptomatic subjects with dyslipidemia and their relatives (n = 234) were assessed for lipids and prothrombotic markers. Individuals were divided into four dyslipidemic phenotypes (DLP) according to apolipoprotein B (apoB) and triglycerides (TG): DLP1 (n = 58, apoB < 1.2 g/l and TG < 1.5 mmol/l), DLP2 (n = 47, apoB < 1.2 g/l and TG ≥ 1.5 mmol/l), DLP3 (n = 31, apoB ≥ 1.2 g/l and TG < 1.5 mmol/l) and DLP4 (n = 98, apoB ≥ 1.2 g/l and TG ≥ 1.5 mmol/l). Associations between prothrombotic markers and risk factors for atherosclerosis, markers of insulin resistance, and the intima-media thickness of the common carotid artery (IMT) were assessed too. Significant differences in PAI-1 between normolipidemic phenotype—DLP1 (62.5 (35.9–82.9) ng/ml) and hypertriglyceridemic phenotypes—DLP2 (82.2 (61.1–122.1) ng/ml, p < 0.01) and DLP4 (91.4 (63.5–111.8) ng/ml, p < 0.001) after adjustment for age, sex and body mass index, were found. Levels of t-PA were different only between DLP1 and DLP4 (1.9 (0.9–3.3) ng/ml vs. 5.3 (2.5–8.6) ng/ml, p < 0.05). There were no significant differences of vWF between DLPs. PAI-1 and t-PA correlated with lipid parameters, markers of insulin resistance, blood pressure and obesity. VWF was independently associated with IMT, which was increased in DLP4. Individuals with hypertriglyceridemic phenotypes showed increased levels of PAI-1 in comparison with normolipidemic subjects. The elevation of t-PA was presented only in patients with simultaneously elevated TG and apoB. The significant increase of IMT confirmed in the patients with DLP4 reveals individuals with the highest risk for atherosclerosis manifestation.     

Gender differences in short-term effects of atorvastatin on lipid profile, fibrinolytic parameters, and endothelial function

Background and aimLittle is known about the impact of gender on short-term effects of atorvastatin. We investigated the gender differences in the short-term lipid-lowering and pleiotropic effects of atorvastatin therapy.Methods and resultsSeventy-two consecutive patients including 48 women with primary hypercholesterolemia, were assigned prospectively to treatment with atorvastatin (10 mg/day) for 3 months. We measured fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS) as marker of lipid peroxide, fibrinolytic parameters, and endothelial function by flow-mediated vasodilation of the brachial artery (FMD), at baseline and after 3 months of therapy. We assessed the impact of gender on temporal differences in these parameters.In men, atorvastatin decreased total, low-density lipoprotein (LDL), and small, dense LDL-cholesterol concentrations, and increased FMD after 3 months. In women, atorvastatin decreased TBARS, triglyceride, and total, LDL, small, dense LDL, and remnant-like lipoprotein particle-cholesterol concentrations, and increased FMD after 3 months. Fibrinolytic parameters did not change significantly in either men or women. With respect to the percent change in those parameters after 3 months, TBARS (−17.6 ± 12.4 vs. −0.4 ± 18.8%, p < 0.01) and small, dense LDL-cholesterol (−96.7 ± 8.3 vs. −68.6 ± 29.7%, p < 0.01) decreased to a greater degree in women, although the relative changes in other parameters were similar between men and women.ConclusionsWe found gender differences in some of the lipid altering changes, including TBARS and small, dense LDL-cholesterol concentrations, after short-term atorvastatin therapy, which were greater in women. However, short-term atorvastatin therapy may be beneficial in improving endothelial function equally in both men and women.     

Blood lipid profile in healthy subjects treated with ticlopidine

The study was carried out in order to evaluate if Ticlopidine induces lipid metabolism changes. Twenty seven healthy subjects were studied, 14 with placebo and 13 with Ticlopidine treatment (500 mg/day), for 30 days. Total cholesterol, HDL cholesterol, triglycerides, apolipoproteins A and B were evaluated before and after treatment. No significant changes of the blood lipid parameters were observed.     

Gender differences in diurnal triglyceridemia in lean and overweight subjects.

AIMS: Increased fasting and postprandial triglyceridemia is one of the cardiovascular risk factors for patients with insulin resistance. Since triglyceride (TG) metabolism largely depends on gender, we have investigated diurnal TG changes in patients with and without overweight, focusing on gender differences. METHODS: Twenty-two males and 22 females with overweight (mean body mass index (BMI) 28.0+/-2.3 kg/m2) measured capillary TG concentrations at six fixed time points on three different days. Diurnal TG profiles were calculated as area under the capillary TG curves (TGc-AUCs). The control group consisted of 24 males and 21 females who were not overweight (mean BMI 22.4+/-1.5 kg/m2). Biochemical and anthropometric parameters associated with insulin resistance were measured. RESULTS: Lean males and lean females had comparable fasting insulin levels (6.9+/-2.6 and 8.1+/-4.7 mU/l, respectively), but females had a more favorable fasting lipoprotein profile when compared to males. Diurnal TG profiles were lower in lean females than in lean males (16.9+/-4.3 vs 20.3+/-5.7 mMh, respectively, P<0.05). Overweight males and females had comparable fasting insulin levels (10.3+/-3.4 and 12.1+/-4.9 mU/l, respectively), which were higher than in lean subjects. Overweight females also had a more favorable fasting lipoprotein profile compared to overweight males. Diurnal TG profiles were similar in overweight females and overweight males (31.1+/-15.6 and 32.9+/-13.2 mMh, respectively). Stepwise multiple regression analysis showed that in both males and females, waist circumference was the strongest determinant of diurnal TG profiles when fasting TG concentrations were excluded from the model (R2=0.49 for males and R2=0.33 for females). These results suggest that overweight resulted in a 'male diurnal TG profile' in females due to abdominal fat accumulation. CONCLUSION: Insulin resistance in overweight subjects partly mitigates the gender differences of fasting and postprandial TG metabolism. The significant positive association between diurnal triglyceridemia and waist circumference supports the view that especially abdominal fat associated with insulin resistance enhances postprandial lipemia.     

Gender differences in the oxygen transport system during maximal exercise in hypertensive subjects

STUDY OBJECTIVES: To analyze gender differences in the oxygen transport system at peak exercise with particular emphasis on the difference in systemic arteriovenous oxygen extraction and in mixed venous oxygen saturation. PATIENTS AND METHODS: Cardiopulmonary graded exercise testing and hemodynamic assessment were performed on a cycle ergometer in 64 hypertensive patients (32 female and 32 male) varying in age from 23 to 64 years. Female and male patients were matched for age and BP. MEASUREMENTS AND RESULTS: Peak oxygen uptake was significantly lower in women than in men, and when expressed in absolute units (L/min: -39%) and when normalized for body mass (mL/min/kg: -33%) or statistically adjusted for height and weight (-29%). This resulted essentially from a significantly lower cardiac output in women, both when expressed in absolute units and when adjusted for body size. At the peripheral level, female patients had a lower arteriovenous oxygen content difference at peak exercise, which resulted from a lower hemoglobin concentration and the inability to decrease mixed venous oxygen saturation to the same level as in men. CONCLUSION: The lower peak oxygen uptake of women results from both central and peripheral factors. The significantly higher value for mixed venous oxygen saturation, which contributes to the lower arteriovenous oxygen difference of women, could result from their smaller muscle mass, lower capillary density, and lower oxidative potential.     

Gender differences in adhering to national guidelines in a community lipid clinic

The aggressive treatment of hypercholesterolemia improves morbidity and mortality in patients with a history of cardiovascular disease irrespective of gender. Electronically tracked data on 4324 patients enrolled in a community lipid clinic were analyzed for gender differences in lipid values and adherence to national guidelines in lipid management. Women were older, more likely to be diabetic and/or hypertensive, and have a family history of coronary heart disease. Women also had higher initial total cholesterol, low-density lipoprotein, and triglyceride levels and were more likely to be at goal at entry for high-density lipoprotein. Men were more likely to have coronary heart disease and lower high-density lipoprotein and were more likely to be at goal at entry for triglyceride level. There were no gender differences in low-density lipoprotein at goal at entry or rate of current smoking. All lipid parameters appeared better with age, irrespective of gender. More men than women reached goal for their low-density lipoprotein (61.5% vs 51.7%) and triglyceride (36.9% vs 25.1%) levels, whereas more women than men reached goal for their high-density lipoprotein (33.1% vs 22.2%). The authors conclude that there are significant gender differences in lipid values at entry to a community lipid clinic and in achieving National Cholesterol Education Program targets following the initiation of therapy. A possible gender-independent survivorship effect exists for low-density lipoprotein and high-density lipoprotein.     

Gender and age differences in the prevalence of coronary artery calcification in 953 Chinese subjects

BACKGROUND: To investigate gender and age differences in coronary artery calcium (CAC) as determined by electron beam computed tomography (EBCT) in a Chinese population. METHODS: Consecutive patients undergoing EBCT were subdivided into groups based on gender and decades of life. They were further subdivided into three groups with respect to symptoms of coronary artery disease: typical, atypical and asymptomatic. Total calcium score was calculated for each patient and means calculated for each subgroup. Groups were then compared with respect to age, gender and symptoms. RESULTS: During the study period, 953 patients (736 men and 217 female) aged 17-86 years (mean 55+/-11 years) underwent EBCT. The prevalence of CAC increased significantly with increasing age. The mean total calcium score also increased with increasing age in males and females of each symptom subgroup. The prevalence of coronary artery calcification was significantly higher in males than females until age in excess of 69 years (p<0.05). The prevalence of coronary artery calcification and mean calcium scores were significantly different between each symptom subgroup (p<0.001) with higher scores and prevalence in patients with typical symptoms of coronary disease. CONCLUSIONS: There is an increase in the prevalence of coronary artery calcification with age in Chinese subjects. Male subjects are more likely than female subjects to have detectable coronary calcification up until an age in excess of 69 years. Patients under the age of 70 years, with typical symptoms of coronary artery disease have a higher prevalence and mean calcium score than those with atypical or no symptoms.     

Role of lifestyle variables on the lipid profile of selected South Indian subjects

ObjectiveTo study the associations between diet, exercise. and the serum lipid profile.Materials and methodsHospital based cross-sectional study. The study participants were selected through purposive sampling. The study participants comprised 316 men and women above 20 years of age from a disease-free cohort and included healthy subjects visiting the lifestyle clinic of CARE Hospitals, Hyderabad, India for health check-up.ResultsAmong the participants of the study, 28.5% of the males and 42.2% of the females had hypercholesterolaemia. Body weight was significantly associated with total cholesterol and low-density lipoprotein (LDL) cholesterol. Of the subjects studied, males had a higher mean calorie and fat intake than the females. A positive association was observed between waist circumference and both total cholesterol and LDL cholesterol. Waist circumference was also positively correlated with systolic and diastolic blood pressure and triglycerides. There was a significant difference in the total cholesterol levels of subjects who exercised and those who were not involved in any physical activity. There was a significant difference between the high-density lipoprotein (HDL) cholesterol values of the subjects based on exercise levels. High-density lipoprotein cholesterol levels were significantly higher in males than in females and this is corroborated by the finding of increased exercise levels in males. Duration of exercise had a significant impact on the total cholesterol levels.ConclusionOur results confirm that diet and exercise routines significantly affect the serum lipid profile. Obesity and overweight constitute a risk factor for the development of hypercholesterolaemia and hypertriglyceridaemia.     

Gender differences in arrhythmias

Electrocardiographic and electrophysiologic differences between men and women have long been noted. Women have a higher intrinsic heart rate than men, along with a longer corrected QT interval and a shorter sinus nodal recovery time. The incidence of and risk factors for a variety of arrhythmias differ between men and women. Atrioventricular nodal reentry tachycardia has a 2:1 female-to-male predominance, while accessory pathways are twice as frequent in men. Although atrial fibrillation is more prevalent in men of all age groups, the absolute numbers of men and women with atrial fibrillation are equal, and the associated morbidity and mortality experienced by women with atrial fibrillation appear to be worse. Women have a lower incidence of sudden cardiac death, and female survivors of sudden cardiac death have a lower frequency of spontaneous or inducible ventricular tachycardia. On the other hand, drug-induced torsade de pointes and symptomatic long QT syndrome have a female predominance. Therefore, greater caution should be used when prescribing QT-prolonging drugs in women. The incidence of arrhythmias is increased during pregnancy, and management of pregnant patients poses a significant challenge. The mechanisms of these gender differences are unclear but may be related to hormonal effects and the shorter QT interval in adult males. Pharmacologic and nonpharmacologic therapies are usually equally efficacious, but the risks of pharmacologic therapy are different in men and women. Atrial fibrillation may be more difficult to treat in women.     

Gender differences in gastroenterology

Balancing professional and personal life can be particularly challenging for young women at the prime of their reproductive years. Young female gastroenterologists were found to work for larger groups, take fewer calls, and receive less compensation than their male counterparts. Getting more women into gastroenterology will be an achievable goal if the needs of female trainees are understood and met.     

Gender differences in psychopharmacology

At least half of all patients with psychiatric disorders are female. Depressive disorders occur twice as often in women than in men. Despite the need for a gender-specific approach in treating psychiatric disorders, little is known about gender issues in psychopharmacology. It has been recognized that women respond better than men to serotonin-modulating substances but that this effect is reversed after menopause. Furthermore, women develop gynecological complications under medication with certain psychopharmacological agents which calls the use of these drugs into question. Side effects such as weight gain, hyperglycemia, cardiac arrhythmias, and sexual dysfunction also occur more frequently in women than in men. Pregnancy is a particularly sensitive aspect. The risk that a mother with a psychiatric disorder could relapse if the drug is discontinued has to be weighed against the risk of the child being born with an anomaly or developing prenatal complications.