Cardiovascular diseases in women: a differentiated view and risk stratification.

Cardiovascular diseases are the main cause of mortality in men and women worldwide, surpassing mortality from all associated neoplasms. In women, its prevalence and mortality increase at menopause, but complications of reproductive age, such as preeclampsia and eclampsia, lead to increased cardiovascular risk throughout their lives. Coronary ischemic disease is is the leading cause of death in Brazil and worldwide, with atherosclerotic disease being the principal pathophysiological mechanism. However, in women, other mechanisms are associated with myocardial ischemia, such as microcirculation disease and/or vasospasm, due to the anatomical and hormonal characteristics of women in different stages of their lives. Knowledge of the most prevalent cardiovascular diseases in women, as well as the specific risk factors, the traditional ones with the greatest impact, and the under-recognized ones, is of fundamental importance in their risk stratification, diagnosis, and management, fundamentally aiming at reducing mortality.

Cardiovascular diseases in women: a differentiated view and risk stratification

SUMMARY Cardiovascular diseases are the main cause of mortality in men and women worldwide, surpassing mortality from all associated neoplasms. In women, its prevalence and mortality increase at menopause, but complications of reproductive age, such as preeclampsia and eclampsia, lead to increased cardiovascular risk throughout their lives. Coronary ischemic disease is is the leading cause of death in Brazil and worldwide, with atherosclerotic disease being the principal pathophysiological mechanism. However, in women, other mechanisms are associated with myocardial ischemia, such as microcirculation disease and/or vasospasm, due to the anatomical and hormonal characteristics of women in different stages of their lives. Knowledge of the most prevalent cardiovascular diseases in women, as well as the specific risk factors, the traditional ones with the greatest impact, and the under-recognized ones, is of fundamental importance in their risk stratification, diagnosis, and management, fundamentally aiming at reducing mortality.

Heterozygosity for a mutation in the growth hormone-releasing hormone receptor gene does not influence adult stature, but affects body composition.

CONTEXT: Biallelic mutations in the GHRH receptor (GHRHR) gene (GHRHR) are a frequent cause of isolated GH deficiency (IGHD). Although heterozygous carriers of these mutations appear normal, we hypothesized that heterozygosity for a GHRHR mutation might be associated with a subclinical phenotype. METHODS: We studied members of a large Brazilian kindred with IGHD (Itabaianinha cohort) caused by a homozygous null GHRHR mutation. We compared 76 adult subjects (age, 25-75 yr) heterozygous for the mutation (WT/MT) with 77 sex-matched controls from the same population who are homozygous for the wild-type GHRHR allele (WT/WT). RESULTS: We found no difference in adult height and sd score for serum IGF-I between the two groups. Body weight, body mass index, skin folds, waist and hip circumferences, and lean mass were all reduced in WT/MT subjects. Percentage fat mass and waist/hip ratio were similar in the two groups. Fasting insulin and homeostasis model assessment of insulin resistance were lower in WT/MT. The other biochemical parameters [total and fractionated cholesterol, triglycerides, lipoprotein (a), and C-reactive protein] were not different between the two groups. CONCLUSIONS: Heterozygosity for a null GHRHR mutation is not associated with reduction in adult stature or in serum IGF-I but is associated with changes in body composition and possibly an increase in insulin sensitivity. These effects do not seem to be modulated by changes in circulating IGF-I.

Congenital growth hormone (GH) deficiency and atherosclerosis: effects of GH replacement in GH-naive adults.

BACKGROUND: GH deficiency (GHD) in adults is associated with increased abdominal adiposity and systolic blood pressure, total and low-density lipoprotein cholesterol, and C-reactive protein. METHODS: We have studied the effects of 6-month GH replacement therapy in 20 adult members of a large Brazilian kindred with lifelong severe and isolated GHD due to a homozygous mutation in GHRH receptor gene (46 +/- 14.5 yr; 122 +/- 7.7 cm; 36.7 +/- 5.4 kg; 10 men). Subjects were studied at baseline, after 6-month bimonthly depot GH injections (Nutropin Depot; Genentech, Inc., South San Francisco, CA) [post GH (pGH)], and after 6- and 12-month washout. RESULTS: Despite modest trough serum IGF-I increase, GH replacement therapy caused a decrease in skinfolds and in waist-hip ratio, with a rebound increase at 12 months. Total and low-density lipoprotein cholesterol were reduced pGH and returned to baseline at 6 months. High-density lipoprotein cholesterol increased pGH, but at 12 months was lower than baseline. A progressive increase in left ventricular mass index, posterior wall, and septum thickness occurred from pGH to 12 months, and of carotid intima-media thickness, from 6 to 12 months. Individuals were 6, 16, and 52 times more likely to have an atherosclerotic carotid plaque at pGH, 6 and 12 months, respectively, when compared with baseline. CONCLUSION: In patients with lifetime isolated GHD, 6-month treatment with GH has reversible beneficial effects on body composition and metabolic profile, but it causes a progressive increase in intima-media thickness and in the number of atherosclerotic carotid plaques.

Depression and Cardiovascular Disease in Women

Abstract The prevalence of depression varies from 1 to 17% in different geographic regions, and its incidence is 70% higher in women than men. Today, depression affects more than 300 million people worldwide, affecting twice as many women from adolescence to adulthood. In addition to this earlier onset, depression in women tends to be more severe. Cardiovascular disease and depression are chronic diseases that have a major impact on cardiovascular and all-cause morbidity and mortality, with evidence of a two-way relationship between them, in which depression is a predictor of cardiovascular disease and vice versa. In females, the degree of illness and prognosis are more severe when both diseases are present, than when diagnosed alone. In patients with acute or chronic cardiovascular disease, especially women, a systematic screening for depression should be considered as a preventive strategy of cardiovascular events, aiming to reduce the risk of future events. There are still no clinical studies designed to assess the impact of antidepressant treatment on cardiovascular outcomes in women.

Lack of evidence of premature atherosclerosis in untreated severe isolated growth hormone (GH) deficiency due to a GH-releasing hormone receptor mutation.

BACKGROUND: GH deficiency (GHD) acquired at adult age as a result of pathological processes of the pituitary gland or the hypothalamus causes changes that are associated with worsening cardiovascular risk. They include increase in abdominal obesity, total and low- density lipoprotein cholesterol, and C-reactive protein. GHD adults also have thickening of the carotid arteries. It has been postulated that GHD is the link between hypopituitarism and the increase in cardiovascular and cerebrovascular mortality observed in hypopituitarism. However, several confounding factors exist, such as associated pituitary deficits and replacement of other hormones or surgical or radiological therapies used to treat the underlying pituitary of hypothalamic pathologies. OBJECTIVE: The aim of this study was to determine the consequences of lifetime isolated GHD (IGHD) on the metabolic and cardiovascular status of adult members of a large Brazilian cohort with severe IGHD due to a homozygous mutation in the GHRH receptor gene. DESIGN: Twenty-two GH naive adult dwarfs (10 men and 12 women; aged 44 +/- 12 yr) were compared with 22 healthy volunteers (10 men and 12 women; aged 45 +/- 12 yr) living in the same area. RESULTS: GHD subjects had increased abdominal obesity, higher total and low-density lipoprotein cholesterol, and higher C-reactive protein than controls. They did not have an increase in carotid wall thickness, and there was no evidence of premature atherosclerosis as evaluated by exercise echocardiography. CONCLUSIONS: In this homogeneous cohort residing in a rural area of Brazil, lifetime, untreated severe IGHD is not associated with evidence of premature atherosclerosis despite unfavorable cardiovascular risk profile.

The REBECGA brazilian registry of pregnancy and heart disease: rationale and design

BACKGROUND: Maternal mortality rates in Brazil remain above the goals established by the United Nations Sustainable Development Goals. Heart disease is estimated to affect 4% of all pregnancies and remains by itself the main indirect obstetric cause of maternal death. In the last decades, a significant improvement in the prognosis of heart diseases has made pregnancy possible in women with heart disease and provided better maternal and fetal outcomes. OBJECTIVES: To establish a multicenter Brazilian Registry of pregnant women with heart disease; to study the causes of immediate and late maternal mortality; and to assess the prevalence of heart disease in the country's macro-regions. METHODS: This is an observational study, with retrospective and prospective stages, of the clinical and obstetric progression of pregnant women with heart disease. These women consecutively received care during pregnancy and will be followed up for up to a year after delivery at public and private hospitals with infrastructure for the execution of this project, a principal investigator, and approval by Ethics and Research Committees. RESULTS: Our results will be presented after data collection and statistical analysis, aiming to demonstrate immediate and late maternal mortality rates, as well as the prevalence of heart disease in the country and its cardiovascular and obstetric complications during pregnancy. CONCLUSIONS: REBECGA will be the Brazilian Registry of heart disease and pregnancy and it will contribute to planning preventive measures, raising financial resources for the improvement of high-risk prenatal care, and reducing immediate and late maternal mortality due to heart disease.

Suspicion of obstructive sleep apnea by Berlin Questionnaire predicts events in patients with acute coronary syndrome.

BACKGROUND: From a mechanistic standpoint, obstructive sleep apnea (OSA) may further disturb cardiovascular homeostasis in the setting of acute coronary syndrome (ACS). OBJECTIVE: We sought to investigate if a standardized clinical diagnosis of OSA, in acute coronary syndrome patients, predicts the risk of cardiovascular events during hospitalization. METHODS: In a prospective cohort study, a group of 200 patients diagnosed with ACS between September 2005 and November 2007 were stratified by the Berlin Questionnaire (BQ) regarding the risk for OSA (high or low risk). We tested if the subgroup of high risk for OSA was prone to a higher frequency of cardiovascular events. The primary endpoint evaluated was a composite outcome of cardiovascular death, recurrent cardiac ischemic events, acute pulmonary edema and stroke during hospitalization. RESULTS: Ninety four (47%) patients assessed by the BQ were likely to have OSA. High risk for OSA was associated with a non-significant higher mortality (4.25% vs 0.94%; p=0.189), but a significant higher incidence of composite cardiovascular events (18.08% vs 6.6%; p=0.016). In the logistic regression model, multivariate predictors of composite cardiovascular events were age (OR= 1.048; 95% CI 1.008 to 1.090; p=0.019), left ventricular ejection fraction (OR= 0.954; 95% CI 0.920 to 0.989; p=0.010), and higher risk for OSA (OR= 3.657; 95% CI 1.216 to 10.996; p=0.021). CONCLUSION: The use of a simple and validated questionnaire (BQ) to identify patients with higher risk for OSA may help in the prediction of cardiovascular outcome during hospitalization. Moreover, our data suggests that OSA is very common in patients with ACS.