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Cardiovascular disease is the leading cause of death in Australian women, as well as men, with clear disparities in treatment and outcomes between the sexes. Moreover, disease pathophysiology differs between the sexes, with women more likely to suffer from microvascular coronary disease, endothelial dysfunction and heart failure with preserved ejection fraction, as compared to men, who are more likely to experience macrovascular disease or heart failure with reduced ejection fraction. Evidence suggests that both traditional and novel cardiovascular risk factors are often under-recognised and under-treated in women. Certain 'traditional' risk factors, including diabetes mellitus and smoking, may also portend a greater risk of cardiovascular disease in women than men. Furthermore, a number of female-specific risk factors have been identified as increasing the risk of cardiovascular disease in women, including pre-term delivery, pre-eclampsia, gestational diabetes, and polycystic ovary syndrome. Currently, these factors are not included in primary prevention risk stratification tools, nor are they routinely considered in a cardiovascular assessment at a clinical level. This represents a missed opportunity, as early identification may allow for risk factor modification and possible amelioration of the disease burden. This review explores the role of traditional, sex-specific and novel risk factors for cardiovascular disease in women, in addition to pathophysiological differences between the sexes, and contributing societal and behavioural factors. These differences argue strongly for a 'precision medicine' approach to cardiovascular disease that includes sex as a key component.

Doxorubicin (Dox), a mainstay of adjuvant breast cancer treatment, is associated with cardiac toxicity in the form of left ventricular dysfunction (LVD), LV diastolic dysfunction, or LV systolic dysfunction. Study objectives were to evaluate the prevalence of LVD in long-term breast cancer survivors treated with Dox and determine if brain-type natriuretic peptide (BNP) may help identify patients at risk for LVD. Patients who participated in prospective clinical trials of adjuvant Dox-based chemotherapy for breast cancer with a baseline left ventricular (LV) ejection fraction evaluation from 1999 to 2006 were retrospectively identified from the St Vincent's University Hospital database. Patients were invited to undergo transthoracic echocardiography, BNP analysis, and cardiovascular (CV) risk factor assessment. LVDD was defined as left atrial volume index >34 mL/m(2) and/or lateral wall E prime <10 m/s, and LVSD as LVEF <50 %. Of 212 patients identified, 154 participated, 19 patients had died (no cardiac deaths), and 39 declined. Mean age was 60.7 [55:67] years. A majority of the patients (128, 83 %) had low CV risk (0/1 risk factors), 21 (13.6 %) had 2 RFs, and 5 (3.2 %) ≥3 RFs. BMI was 27.2 ± 4.9 kg/m(2). Median Dox dose was 240 mg/m(2) [225-298]; 92 patients (59.7 %) received ≤240 mg/m(2) and 62 (40.3 %) > 240 mg/m(2). Baseline LVEF was 68.2 ± 8 %. At follow-up of 10.8 ± 2.2 years, LVEF was 64.4 ± 6 %. Three (1.9 %) subjects had LVEF <50 % and one (0.7 %) had LVDD. Dox >240 mg/m2 was associated with any LVEF drop. BNP levels at follow-up were 20.3 pg/ml [9.9-36.5] and 21.1 pg/ml [9.8-37.7] in those without LVD and 61.5 pg/ml [50-68.4] in those with LVD (p = 0.04). Long-term prospective data describing the impact of Dox on cardiotoxicity are sparse. At over 10 years of follow-up, decreases in LVEF are common, and dose related, but LVD as defined is infrequent (2.6 %). Monitoring with BNP for subclinical LVD needs further evaluation.

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