Modifiable risk factors and cardiovascular outcomes

To the Editor: The results of an investigation of risk factors on the incidence of cardiovascular disease and death from any cause, as reported by Magnussen et al. on behalf of the Global Cardiovascular Risk Consortium (Oct. 5 issue), show that these risk factors accounted for a population-attributable fraction of the 10-year incidence of cardiovascular disease of 52.6% among men and 57.2% among women. The factors that were investigated are five modifiable risk factors (body-mass index, systolic blood pressure, the level of non–high-density lipoprotein [HDL] cholesterol, current smoking, and diabetes). It is disappointing that current smoking and diabetes were selected

Heart valve prostheses in pregnancy: Outcomes for women and their babies

Background: As the prognosis of women with prosthetic heart valves improves more of these individuals are contemplating and undertaking pregnancy. Accurate knowledge of perinatal outcomes is essential, assisting counselling and guiding care. The aim of this study was to assess outcomes in a contemporary population of women with heart valve prostheses undertaking pregnancy, and to compare outcomes for women with mechanical and bioprosthetic prostheses. Method and results: Longitudinally-linked population health datasets containing birth and hospital admissions data were obtained for all women giving birth in New South Wales, Australia, 2000-2011. This included information identifying presence of maternal prosthetic heart valve. Cardiovascular and birth outcomes were evaluated. Among 1 144 156 pregnancies, 136 involved women with a heart valve prosthesis (1 in 10 000). No maternal mortality was seen among these women, although the relative risk for an adverse event was higher than the general population, including severe maternal morbidity (13.9% v. 1.4%, RR=9.96, 95% CI 6.32-15.7), major maternal cardiovascular event (4.4% v. 0.1%, RR 34.6, 95% CI 14.6-81.6), preterm birth (18.3% v. 6.6%, RR=2.77, 95% CI 1.88-4.07) and small-for-gestational-age infants (19.3% v. 9.5%, RR=2.12, 95% CI 1.47-3.06). There was a trend towards increased maternal and perinatal morbidity in women with a mechanical valve compared to bioprosthetic. Conclusions: Pregnancies in women with a prosthetic heart valve demonstrate an increased risk of an adverse outcome, for both mothers and babies, compared with pregnancies in the absence of heart valve prostheses. In this contemporary population, the risk was lower than previously reported.NHMRC 1001066, NHMRC 1021025, NHMRC 1062262, ARC FT120100069, Australian Heart Foundatio

Heart valve prostheses in pregnancy: Outcomes for women and their babies

Background: As the prognosis of women with prosthetic heart valves improves more of these individuals are contemplating and undertaking pregnancy. Accurate knowledge of perinatal outcomes is essential, assisting counselling and guiding care. The aim of this study was to assess outcomes in a contemporary population of women with heart valve prostheses undertaking pregnancy, and to compare outcomes for women with mechanical and bioprosthetic prostheses. Method and results: Longitudinally-linked population health datasets containing birth and hospital admissions data were obtained for all women giving birth in New South Wales, Australia, 2000-2011. This included information identifying presence of maternal prosthetic heart valve. Cardiovascular and birth outcomes were evaluated. Among 1 144 156 pregnancies, 136 involved women with a heart valve prosthesis (1 in 10 000). No maternal mortality was seen among these women, although the relative risk for an adverse event was higher than the general population, including severe maternal morbidity (13.9% v. 1.4%, RR=9.96, 95% CI 6.32-15.7), major maternal cardiovascular event (4.4% v. 0.1%, RR 34.6, 95% CI 14.6-81.6), preterm birth (18.3% v. 6.6%, RR=2.77, 95% CI 1.88-4.07) and small-for-gestational-age infants (19.3% v. 9.5%, RR=2.12, 95% CI 1.47-3.06). There was a trend towards increased maternal and perinatal morbidity in women with a mechanical valve compared to bioprosthetic. Conclusions: Pregnancies in women with a prosthetic heart valve demonstrate an increased risk of an adverse outcome, for both mothers and babies, compared with pregnancies in the absence of heart valve prostheses. In this contemporary population, the risk was lower than previously reported.NHMRC 1001066, NHMRC 1021025, NHMRC 1062262, ARC FT120100069, Australian Heart Foundatio

Prosthetic heart valves in pregnancy, outcomes for women and their babies: A systematic review and meta-analysis

Background Historically, pregnancies among women with prosthetic heart valves have been associated with an increased incidence of adverse outcomes. While there have been advances in prosthetic heart valve design, obstetric and medical care, subsequent impact on incidence of adverse outcomes during pregnancy has not been quantified. Objectives To assess the risk of adverse pregnancy outcomes among women with a prosthetic heart valve(s) in the contemporary setting. Search Strategy Electronic literature search of Medline, The Cochrane Library, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and Embase to find recent studies. Selection Criteria Studies of pregnant women with heart valve prostheses including trials, cohort studies and unselected case series. Data Collection and Analysis Absolute risks and 95% confidence intervals for pregnancy outcomes were calculated using either a random effects model or the logit transformation of total events and participants (the latter method when multiple studies had event counts of zero). Main Results Eleven studies capturing 499 pregnancies among women with heart valve prostheses were eligible for inclusion. Pooled maternal mortality rate was 0.8/100 pregnancies (95% CI 0.3-2.1), pregnancy loss rate 32.1/100 pregnancies (95% CI 28.1-36.3) and perinatal mortality rate 4.7/100 births (95% CI 2.7-7.9). Conclusions Women with heart valve prostheses experienced higher rates of adverse outcomes then would be expected in a general obstetric population, however lower than previously reported. Multidisciplinary pre-pregnancy counselling and vigilant cardiac and obstetric surveillance throughout the perinatal period remains warranted for these women and their infantsNHMRC 1001066, NHMRC 1021025, NHMRC 1062262, ARC FT120100069 and Australian Heart Foundatio

Polygenic risk score and coronary artery disease:A meta-analysis of 979,286 participant data

BACKGROUND AND AIMS: Coronary artery disease (CAD) is a complex disease with a strong genetic basis. While previous studies have combined common single-nucleotide polymorphisms (SNPs) into a polygenic risk score (PRS) to predict CAD risk, this association is poorly characterised. We performed a meta-analysis to estimate the effect of PRS on the risk of CAD. METHODS: Online databases were searched for studies reporting PRS and CAD. PRS computation was based on log-odds (PRSLN), pruning or clumping and thresholding (PRSP/C + T), Lassosum regression (PRSLassosum), LDpred (PRSLDpred), or metaGRS (PRSmetaGRS). The reported odds ratio (OR), hazard ratio (HR), C-indexes and their corresponding 95% confidence interval (95% CI) were pooled in a random-effects meta-analysis. RESULTS: Forty-nine studies were included (979,286 individuals). There was a significant association between 1-standard deviation [SD] increment in PRS and adjusted risks of both incident and prevalent CAD (OR [95% CI]: 1.67 [1.57-1.77] for PRSmetaGRS, 1.46 [1.26-1.68] for PRSLDpred). The risk of incident CAD was highest for PRSP/C + T (HR [95% CI]: 1.49 [1.26-1.78]), PRSmetaGRS (1.37 [1.27-1.47]), and PRSLDpred (1.36 [1.31-1.42]). Analysis of model performance demonstrated that PRS predicted incident CAD with C-index of up to 0.71. Importantly, addition of PRS to clinical risk scores resulted in modest but statistically significant improvements in CAD risk prediction, with 1.5% observed for PRSP/C + T (p < 0.001) and 1.6% for PRSLDpred (p < 0.001). CONCLUSIONS: Polygenic risk score is strongly associated with increased risks of CAD. Future prospective studies should explore the usefulness of polygenic risk scores for identifying individuals at a high risk of developing CAD

Endothelial cell dysfunction: Implications for the pathogenesis of peripheral artery disease

Peripheral artery disease (PAD) is caused by occluded or narrowed arteries that reduce blood flow to the lower limbs. The treatment focuses on lifestyle changes, management of modifiable risk factors and vascular surgery. In this review we focus on how Endothelial Cell (EC) dysfunction contributes to PAD pathophysiology and describe the largely untapped potential of correcting endothelial dysfunction. Moreover, we describe current treatments and clinical trials which improve EC dysfunction and offer insights into where future research efforts could be made. Endothelial dysfunction could represent a target for PAD therapy

A hidden problem: peripheral artery disease in women

Peripheral artery disease (PAD) has a huge social and economic burden and is an important contributor to the global health burden. Sex differences in PAD are apparent, with recent data suggesting equal if not greater prevalence in women, and women having worse clinical outcomes. Why this occurs is not clear. To identify underlying reasons for gender inequalities in PAD, we executed a deeper exploration through a social constructive perspective. A scoping review was conducted using the World Health Organization model for analysis of gender-related needs in healthcare. Complex interacting factors, including biological, clinical, and societal variables, were reviewed to highlight gender-related inequities in the diagnosis, treatment, and management of PAD. Current gaps in knowledge were identified and insights into future directions aimed at improving these inequalities were discussed. Our findings highlight the multi-level complexities that need to be considered for strategies to improve gender-related needs in PAD healthcare

Sex, Endothelial Cell Functions, and Peripheral Artery Disease

Peripheral artery disease (PAD) is caused by blocked arteries due to atherosclerosis and/or thrombosis which reduce blood flow to the lower limbs. It results in major morbidity, including ischemic limb, claudication, and amputation, with patients also suffering a heightened risk of heart attack, stroke, and death. Recent studies suggest women have a higher prevalence of PAD than men, and with worse outcomes after intervention. In addition to a potential unconscious bias faced by women with PAD in the health system, with underdiagnosis, and lower rates of guideline-based therapy, fundamental biological differences between men and women may be important. In this review, we highlight sexual dimorphisms in endothelial cell functions and how they may impact PAD pathophysiology in women. Understanding sex-specific mechanisms in PAD is essential for the development of new therapies and personalized care for patients with PAD