Alice Y. Chang

Higher Natriuretic Peptide Levels Associate With a Favorable Adipose Tissue Distribution Profile

OBJECTIVES The goal of this study was to investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort. BACKGROUND Natriuretic peptides stimulate lipolysis, reduce weight gain, and promote adipocyte browning in animal models, but data are lacking in humans. METHODS A total of 2,619 participants without heart failure in the Dallas Heart Study underwent measurements of 1) B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP); and 2) body fat distribution by dual energy x-ray absorptiometry and magnetic resonance imaging. Cross-sectional associations of natriuretic peptides with adiposity phenotypes were examined after adjustment for age, sex, race, comorbidities, and body mass index. RESULTS Median BNP and NT-proBNP levels in the study cohort (mean age 44 years; 56% women, 48% African Americans, 32% obese) were 3.0 and 28.1 pg/ml, respectively. Natriuretic peptide levels above the median were associated with a more favorable body fat profile and less insulin resistance, including lower visceral fat, liver fat, and homeostasis model assessment of insulin resistance index, and increased lower body fat and higher adiponectin (p < 0.05 for each). In multivariable analyses, NT-proBNP remained inversely associated with visceral fat (beta coefficient = -0.08; p < 0.0001) and liver fat (beta coefficient = -0.14; p < 0.0001) and positively associated with lower body fat (beta coefficient = 0.07; p < 0.0001) independent of age, sex, race, and obesity status; findings were similar with BNP. Adjustment for body composition, homeostasis model assessment of insulin resistance index, circulating androgens, and adipocytokines did not attenuate the associations. CONCLUSIONS Higher natriuretic peptide levels were independently associated with a favorable adiposity profile, characterized by decreased visceral and liver fat and increased lower body fat, suggesting a link between the heart and adipose tissue distribution mediated through natriuretic peptides.

Polycystic ovarian syndrome and subclinical atherosclerosis among women of reproductive age in the Dallas heart study

Objective  Polycystic ovarian syndrome (PCOS), the most common endocrinopathy of young women, is characterized by androgen excess and is frequently associated with cardiovascular risk factors. However, it is unclear whether PCOS is a risk factor for atherosclerosis. We sought to determine in a multiethnic population‐based sample whether women with PCOS have greater measures of subclinical atherosclerosis than women without PCOS.

46,XX DSD: the masculinised female

The 46,XX disorders of sex development (DSDs) cause virilisation or masculinisation of the female foetus. The final common pathway of all 46,XX DSDs is excess dihydrotestosterone (DHT) or potent foreign androgen in the genital tissue during the critical period of sexual differentiation. Whereas the foetal testis is source of androgen in the male, it is the foetal adrenal that produces the DHT precursors in the female. By understanding the principles of human steroid biosynthesis, the pathogenesis of each disorder may be logically deduced, and treatment strategies are rationally constructed. In practice, however, therapies for many of these diseases are fraught with complications and caveats, and current approaches leave much room for improvement. This review discusses these diseases, their pathogenesis and approaches to therapy. We emphasise areas where improved treatments are sorely needed.

Clinical Characteristics, Vascular Function, and Inflammation in Women With Angina in the Absence of Coronary Atherosclerosis: The Dallas Heart Study

OBJECTIVES we sought to evaluate the relationship between angina and coronary artery calcium (CAC) in women, and among women without CAC, the associations between angina and clinical, vascular, and inflammatory factors. BACKGROUND angina in women without coronary atherosclerosis is associated with significant morbidity, yet its determinants are poorly understood. METHODS women ages 30 to 65 years from the Dallas Heart Study, a multiethnic probability sample of Dallas County residents, who completed a Rose angina questionnaire and had complete data for CAC by computed tomography were selected for this analysis. Soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, high sensitivity C-reactive protein, monocyte chemoattractant protein-1 and aortic compliance by magnetic resonance imaging were measured. RESULTS among the 1,480 women in this cohort (mean age 45 years, 49% African-American), angina was present in 6.9% but was not associated with CAC (19% CAC prevalence with angina vs. 15% without, p = 0.2). Among women without CAC, angina was related to variables reflecting obesity and insulin resistance and was independently associated with African-American ethnicity, premature family history of myocardial infarction, and waist circumference (all p < 0.05). Such women with angina also had higher levels of soluble intercellular adhesion molecule-1 (668 vs. 592 ng/ml, p = 0.02) and soluble vascular cell adhesion molecule-1 (1,106 vs. 968 ng/ml, p = 0.01) and reduced aortic compliance (mean 22 vs. 26 ml/mm Hg, p = 0.007) than such women without angina. Conversely, there was no difference in C-reactive protein or monocyte chemoattractant protein-1 levels for women with and without angina (p = not significant, each). CONCLUSIONS angina among women in the general population is common and is not associated with subclinical atherosclerosis. Additionally, angina in the absence of subclinical atherosclerosis is not related to many traditional atherosclerotic risk factors but is associated with clinical, inflammatory, and vascular factors that reflect endothelial dysfunction and vascular stiffness, suggesting a distinct vascular etiology and alternative potential therapeutic targets.

Hyperthyroidism-Associated Coronary Vasospasm with Myocardial Infarction and Subsequent Euthyroid Angina

A 40-year-old African-American woman presented with atypical chest pain, an acute non-ST segment elevation myocardial infarction, and angiographic evidence for severe ostial vasospasm of the left main and right coronary arteries. Subsequently, she was diagnosed with hyperthyroidism and treated with antithyroid therapy and oral nitrates. Repeat angiography revealed resolution of the vasospasm; however, the chest pain recurred in the euthyroid state. Hyperthyroidism-associated coronary vasospasm is a rare disorder that characteristically causes angina in young Asian women and resolves with correction of hyperthyroidism. We present an atypical case of an African-American woman presenting with a myocardial infarction who developed recurrent angina while euthyroid.

Influence of race/ethnicity on cardiovascular risk factors in polycystic ovary syndrome, the Dallas Heart Study.

Polycystic ovarian syndrome (PCOS) is estimated to affect up to 20% of women. PCOS is associated with insulin resistance and cardiovascular (CV) risk factors. We aimed to evaluate the impact of race/ethnicity on the prevalence of CV risk factors and subclinical predictors of CV events.

Dehydroepiandrosterone replacement therapy--panacea, snake oil, or a bit of both?

Age-related declines in dehydroepiandrosterone sulfate concentration parallel the physical and cognitive changes of aging. This observation suggests that these events are causally related and that replacement therapy might have beneficial effects in the elderly. The authors of this Viewpoint consider the evidence for, and against, such an approach.

Endocrine Disturbances Affecting Reproduction

Abstract The reproductive axis, particularly in women, is vulnerable to disruption from environmental influences and illness. Endocrine disorders not involving the gonads strongly influence reproductive function. Diseases of the pituitary, adrenal, and thyroid can exert deleterious effects on ovulation, sex steroid production, implantation, and pregnancy outcomes. This chapter will review the presenting features, evaluation, and treatment of major endocrine disorders that affect reproduction, with emphasis on mechanisms that impair fertility.

Venus and the heart: Endocrine influences on cardiovascular health in women

The influence of gonadal steroids on the heart and vascular system represents the crossroads of reproductive science and cardiology. This field has received considerable attention as the genesis of the observed difference in cardiovascular risk born by men and women. The unexpected initial results of the Women’s Health Initiative (WHI) study rocked the field when estrogens did not appear to provide the beneficial effects on heart disease anticipated by prior epidemiologic studies. The results of this study, their interpretation, and extrapolation to other groups of women have likewise received ample attention during the years subsequent to the first WHI publication. Nevertheless, the WHI provided a wake-up call to investigators in the field to recognize the complexity of the physiologic connections between gonadal steroids and cardiovascular health. Although estrogens have for a long time drawn the most attention in the debates surrounding the influence of gonadal steroids on the heart, androgens have more recently staged a comeback, and with good reason. First of all, circulating concentrations of estradiol are generally only twoto fourfold higher in women than in men, except during ovulation and pregnancy. In contrast, androgens are an order of magnitude higher in men than in women, and free testosterone can be 50 times higher. Second, androgen excess states have been associated with increased cardiovascular risk, with polycystic ovary syndrome (PCOS) being the best example. Strangely, androgen deficiency (rather than excess) in men has also been associated with increased cardiovascular risk. Consequently, the response of the cardiovascular system in men and women to androgens and estrogens appears to Alice Y. Chang, M.D., M.S. Richard J. Auchus, M.D., Ph.D.