Prevention of anthracycline and trastuzumab-induced decline in left ventricular ejection fraction with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker: a narrative systematic review of randomised controlled trials.

Cancer therapy-related cardiac dysfunction (CTRCD) is a complication of selected cancer therapy agents associated with decline in left ventricular ejection fraction (LVEF). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have established benefits in heart failure with reduced ejection fraction, but their efficacy for preventing CTRCD remains controversial. This narrative systematic review assessed the efficacy and safety of ACEI/ARB in the prevention of cancer therapy LVEF decline. We systematically searched PubMed, Embase and Cochrane from January 1980 to June 2022. Studies of interest were randomised controlled trials of patients with normal LVEF and active malignancy receiving cancer therapy, randomised to receive either an ACEI or ARB compared with a control group. The outcome was the change in LVEF from baseline to the end of the follow-up period. Death, clinical heart failure and adverse drug reactions were recorded. A total of 3731 search records were screened and 12 studies were included, comprising a total of 1645 participants. Nine studies assessed the prevention of anthracycline-induced LVEF decline, of which five showed a beneficial effect (1%-14% higher LVEF in treated groups), whereas four studies showed no effect. Three studies assessed the prevention of trastuzumab-induced LVEF decline, of which one showed a beneficial effect (4% higher LVEF) in a subset of participants. There are mixed data regarding the efficacy of ACEI/ARB in preventing the LVEF decline in patients undergoing anthracycline or trastuzumab therapy, with evidence suggesting no clinically meaningful benefit observed in recent studies.

Comparison of four risk scores for contemporary isolated coronary artery bypass grafting.

BACKGROUND: EuroSCORE and the Society of Thoracic Surgeons' (STS) Score have been the most widely used risk scores for cardiac surgery. The revised EuroSCORE II and the AusSCORE, based on an Australasian population, were recently developed. We compared the prognostic utility of these four scores for mortality as well as morbidity in patients undergoing isolated coronary artery bypass grafting (CABG). METHODS: The scores were retrospectively calculated for isolated CABG patients at Auckland City Hospital during July 2010-June 2012. Discrimination and calibration of outcomes were assessed. RESULTS: 818 patients were followed for 1.6+/-0.6 years. Mortality at 30 days was 1.6% and 2.9% on follow up. Median predicted 30 day mortality (Interquartile range) for EuroSCORE I were 2.8% (1.6%, 5.2%), EuroSCORE II 1.6% (1.0%, 2.8%), STS Score 2.3% (1.3%, 4.5%) and AusSCORE 0.5% (0.2%, 1.1%). C-statistics and Hosmer-Lemeshow test p-values for these scores for 30-day mortality were Euro score I 0.675 (95%CI 0.531-0.819)/0.061, EuroSCORE II 0.642 (0.503-0.780)/0.150, STS Score 0.641 (0.507-0.775)/0.243 and AusSCORE 0.661 (0.516-0.807)/0.420. Only EuroSCORE I and STS scores were significant for predicting mortality at follow-up (c=0.639 and 0.666). All scores predicted composite morbidity. C-statistics were EuroSCORE I 0.678, EuroSCORE II 0.634, STS score 0.584 and AusSCORE 0.645. CONCLUSION: EuroSCORE II, STS Score and AusSCORE had slightly improved calibration but similar discrimination for 30-day mortality compared to EuroSCORE I. Revision of risk models to fit contemporary surgical outcomes is important, but there may only be modest room for improvement in discrimination.

Stable bone density in HAART-treated individuals with HIV: a meta-analysis.

CONTEXT: Longitudinal studies of bone mineral density (BMD) in HIV have reported conflicting results. OBJECTIVE: We investigated whether temporal changes in BMD differ by highly active antiretroviral therapy (HAART) status at baseline. DATA SOURCES: Data sources included MEDLINE, EMBASE, and the Web of Science for English language studies (1966 to September 2010) and conference abstracts (1997-2010). STUDY SELECTION: Longitudinal studies reporting BMD at least 48 wk apart in adult patients with HIV with a comparable uninfected control group were eligible. Uncontrolled studies were included in secondary analyses. DATA EXTRACTION: Data were independently extracted by two researchers. DATA SYNTHESIS: Data were pooled using random-effects models. In the primary analysis of six controlled studies (follow-up 1.5-2.7 yr), there were no significant differences in the percent change from baseline in BMD at the total hip or femoral neck between HIV cohorts and controls and a decrease of 0.6% (95% confidence interval = -1.1 to -0.1) at the spine in the HIV cohorts. In the secondary analysis of 37 studies (31 uncontrolled, six controlled), cohorts treated with HAART at baseline had stable or slight increases in BMD at 1 yr, stable or slight decreases in BMD at 2 yr, and stable BMD at 2.5 yr or later. In cohorts that were HAART-naive/untreated at baseline, there was accelerated loss of BMD at all time points, and the annualized rate of BMD change was greatest at 1 yr, but thereafter decreased. CONCLUSION: BMD is stable in HIV cohorts established on HAART, whereas cohorts initiating HAART have short-term accelerated BMD loss followed by a longer period of BMD stability/increases. Routine monitoring of BMD in many HAART-treated patients may not be necessary.

Relationships between vascular calcification, calcium metabolism, bone density, and fractures.

Factors involved with calcium metabolism, such as serum calcium and phosphate and calcium intake, have been associated with vascular disease in different populations. We investigated whether this association is mediated via increased vascular calcification by assessing relationships between these factors and abdominal aortic calcification (AAC) and coronary artery calcification (CAC). A total of 1471 healthy postmenopausal women participated in a 5-year randomized, placebo-controlled trial of calcium 1 g/day, and 323 healthy middle-aged and older men participated in a 2-year randomized, placebo-controlled trial of calcium 600 or 1200 mg/day. AAC was assessed on vertebral morphometric images at baseline and follow-up. Based on computed tomography, 163 men had CAC assessed, on average, 1.5 years after study completion. In elderly women, AAC was positively related to serum calcium (p < .001), phosphate (p = .04), and the calcium-phosphate product (p = .003), but changes in AAC over time and incidence of cardiovascular events were not related to these variables. In middle-aged men, AAC and CAC were not consistently related to these variables. Neither dietary calcium intake nor calcium supplementation was associated with changes in the prevalence of AAC over time, and calcium supplementation also was not related to CAC scores in men. After adjusting for age, AAC was not associated with low bone mineral density (BMD) at baseline, changes in BMD over time, or fracture incidence. CAC also was not related to baseline BMD. In summary, serum calcium and phosphate are associated with AAC in older women, but dietary calcium intake and calcium supplementation were not associated with changes in AAC over 2 to 5 years.

Abdominal aortic calcification on vertebral morphometry images predicts incident myocardial infarction.

Abdominal aortic calcification (AAC) measured on spine X-rays is an established risk factor for cardiovascular disease. We investigated whether AAC assessed using vertebral morphometry and a recently developed scoring system (AAC-8) is reliable and associated with cardiovascular risk factors or events. A total of 1471 healthy postmenopausal women and 323 healthy middle-aged and older men participated in 5 and 2 year trials of calcium supplements, respectively. AAC-8 was assessed on vertebral morphometry images at baseline and follow-up. In addition, 163 men also had coronary artery calcification measured using computed tomography. Cardiovascular events during the trials were independently adjudicated. We found strong inter- and intrameasurer agreement for AAC-8 (kappa > 0.87). The prevalence of AAC increased with age (p < .01) in women and in men. AAC was associated with many established cardiovascular risk factors, with serum calcium in women (p = .002) and with higher coronary calcium scores in men (p = .03). Estimated 5 year cardiovascular risk increased with increasing AAC-8 score (p < .001) in women and in men. The presence of AAC independently predicted myocardial infarction (MI) in women [hazards ratio (HR) = 2.30, p = .007] and men (HR = 5.32, p = .04), even after adjustment for estimated cardiovascular risk in women. In women, AAC independently predicted cardiovascular events (MI, stroke, or sudden death) (HR = 1.74, p = .007), and changes in AAC-8 score over time were associated with MI and cardiovascular events, even after adjustment for estimated cardiovascular risk. In summary, scoring AAC on vertebral morphometric scans is a reproducible method of assessing cardiovascular risk that independently predicts incident MI and cardiovascular events, even after taking into account traditional cardiovascular risk factors.