Anabolic steroid abuse in athletes has been associated with a wide range of adverse conditions, including hypogonadism, testicular atrophy, impaired spermatogenesis, gynaecomastia, and psychiatric disturbance. But what effect does steroid abuse have on the cardiovascular system?

Background-Estrogen receptor ␣ (ESR1) gene variation is associated with a range of important estrogen-dependent characteristics, including responses of lipid profile and atherosclerotic severity to hormone replacement therapy, coronary heart disease risk, and migraine. The roles that reproductive steroids play in cerebrovascular pathophysiology and ischemia are an important area of investigation.

Understanding the mechanisms by which estrogens affect cardiovascular disease risk, including the role of variation in the gene for estrogen receptor ␣ (ESR1), may be key to new treatment strategies. We investigated whether the CC genotype at ESR1 c.454-397T>C is associated with increased risk among men. Study of more than 7000 whites in 5 cohorts from 4 countries provided evidence that genotype CC, present in roughly 20% of individuals, is a risk factor for nonfatal acute myocardial infarction (odds ratio‫;44.1؍‬ P<0.0001), after adjustment for established cardiovascular risk factors. After exclusion of younger subjects from 2 cohorts, because of age interaction, the odds ratio increased (to 1.63).I n the Rotterdam Study, an estrogen receptor ␣ (ESR1) haplotype, including the ESR1 c.454-397 T allele, also referred to in previous studies as the p allele of the PvuII site in intron 1 (rs2234693), was associated with significantly increased risk of myocardial infarction (MI) among postmenopausal women (for homozygous carriers, the relative risk was 2.48; the 95% confidence interval [CI] Materials and MethodsWe included only cohorts of white men not recruited on the basis of coronary heart disease risk factors (Table I in the online data supplement, available at http://circres.ahajournals.org). We studied men from the prospective population-based Second Northwick Park Heart Study (NPHSII) in the United Kingdom 4 and 2 case-control studies of MI from Poland and the United States, selected from the Global Repository at Genomics Collaborative. 5 Here we present a metaanalysis of the results of these studies and published results from the Framingham 3 and Rotterdam Studies 1 : a total of more than 7000 men with detailed covariate information, including 731 men with acute, nonfatal MI. We also carried out analyses of total MI, including 47 fatal MIs in NPHSII and the Rotterdam Study, and ischemic heart disease (IHD) in the 3 prospective studies. Unless specified, odds ratios (ORs) are from a fixed effects model, adjusted for age, body mass index, serum total cholesterol level, hypertension, diabetes, and smoking status. ResultsThe mean (SD) values for age (supplemental Table I Figure). Power was low for detection of an association with fatal MI, with 20% power to detect an effect of the size seen in the nonfatal MIs. Of 47 fatal MIs, only 4 (8.5%) had an ESR1 c.454-397CC genotype. When fatal MIs were included in the Rotterdam and NPHSII analyses, the ORs for total MI were 1.11 (95% CI, 0.72 to 1.71) and 1.23 (95% CI, 0.83 to 1.82), respectively, with the pooled OR 1.31 (95% CI, 1.07 to 1.59; Pϭ0.008). After exclusion of total MI, the combined IHD result from the 3 prospective studies was not significant, pooled ORϭ0.90 DiscussionSixty-eight percent of the weight of our model for nonfatal MI is derived from previously unstudied cohorts, making it unlikely that our results have been affected by publication bias. Our findings also show consistency across 5 white cohorts from 4 countries, providing additional evidence th...

Background and AimsAnthracyclines are highly effective chemotherapeutic agents which may cause long-term cardiac damage (chronic anthracycline cardiotoxicity) and heart failure. The pathogenesis of anthracycline cardiotoxicity remains incompletely understood and individual susceptibility difficult to predict. We sought clinical features which might contribute to improved risk assessment.MethodsSubjects were women with early breast cancer, free of pre-existing cardiac disease. Left ventricular ejection fraction was measured using cardiovascular magnetic resonance before and >12 months after anthracycline-based chemotherapy (>3 months post-Trastuzumab). Variables associated with subclinical cardiotoxicity (defined as a fall in left ventricular ejection fraction of ≥5%) were identified by logistic regression.ResultsOne hundred and sixty-five women (mean age 48.3 years at enrollment) completed the study 21.7 months [IQR 18.0–26.8] after starting chemotherapy. All received anthracyclines (98.8% epirubicin, cumulative dose 400 [300–450] mg/m2); 18% Trastuzumab. Baseline blood pressure was elevated (≥140/90mmHg, mean 147.3/86.1mmHg) in 18 subjects. Thirty-four subjects (20.7%) were identified with subclinical cardiotoxicity, independent predictors of which were the number of anthracycline cycles (odds ratio, OR 1.64 [1.17–2.30] per cycle), blood pressure ≥140/90mmHg (OR 5.36 [1.73–17.61]), body surface area (OR 2.08 [1.36–3.20] per standard deviation (0.16m2) increase), and Trastuzumab therapy (OR 3.35 [1.18–9.51]). The resultant predictive-model had an area under the receiver operating characteristics curve of 0.78 [0.70–0.86].ConclusionsWe found subclinical cardiotoxicity to be common even within this low risk cohort. Risk of cardiotoxicity was associated with modestly elevated baseline blood pressure–indicating that close attention should be paid to blood pressure in patients considered for anthracycline based chemotherapy. The association with higher body surface area suggests that indexing of anthracycline doses to surface area may not be appropriate for all, and points to the need for additional research in this area.

Background: Increasing left ventricular mass is a risk factor for cardiovascular morbidity and mortality. Objective: To examine the possible association of smoking with the left ventricular growth response in men. Methods: Left ventricular mass was measured in 309 army recruits before and after an identical 12-week physical training programme. Left ventricular mass was determined using cardiovascular magnetic resonance.Results: Left ventricular mass increased with training (mean (standard deviation (SD)) 3.83 (10.81) g, p,0.001). By univariate analysis, exercise-induced change in left ventricular mass was positively associated with cigarette smoking (mean (SD) 1.69 (11.10) g v 4.76 (10.23) g for non-smokers v ex-and current smokers, respectively; p = 0.026), whereas age, height, diastolic and systolic blood pressure (SBP), alcohol consumption or indices of physical activity were not significantly associated with change in left ventricular mass. Multivariate analysis showed body weight, smoking status and SBP to be independent predictors of left ventricular mass (incremental R 2 = 3.4%, p = 0.004; R 2 = 4.9%, p = 0.024; and R 2 = 1.7%, p = 0.041, respectively). Conclusions: Cigarette smoking and SBP are associated with exercise-induced left ventricular growth in young men. The positive association of smoking with changes in left ventricular mass is surprising, given the limited exposure of these subjects to smoking, and although these data do not prove causation, they are of great interest to those trying to uncover the drivers of left ventricular hypertrophy, as well as to those examining the possible ill-effects of smoking in the young.

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Chronic heart failure is a common disorder placing significant burdens on patients and health-care services. Noninvasive imaging plays a central role in accurate diagnosis, determination of etiology and prognosis, and in monitoring therapy. Advances in technology mean cardiovascular magnetic resonance (CMR) imaging has established itself as both a valuable clinical and research tool in this arena. Not only is CMR the new gold standard for accurate and reproducible assessment of ventricular volumes and mass, but by using gadolinium contrast, underlying pathology can often be determined. In ischemic cardiomyopathy a 'one stop' assessment can be made of function, perfusion and mass. Continuing advances such as myocardial tagging and the increasing availability of CMR mean that it will become an increasingly important and useful tool for clinicians looking after patients with cardiomyopathy and heart failure.

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