Prediction Model Based on Easily Available Markers for Aberrant Cardiac Remodeling in Women After Pregnancy.

BACKGROUND: Preeclampsia is strongly associated with left ventricular concentric remodeling (LVCR) and left ventricular hypertrophy (LVH) up to 10 years after delivery. This predisposes to heart failure later in life. Adequate detection and prediction of LVCR or LVH is expected to decrease the risk of developing clinical heart failure within this high-risk female population. Therefore, we developed and internally validated a prediction model for aberrant cardiac remodeling in formerly pregnant women. METHODS: This large cohort study included women with a history of preeclampsia or normotensive pregnancy within a postpartum interval of 6 months to 30 years. Cardiovascular assessment was performed, including echocardiography, 30-minute blood pressure measurements, and circulating biomarkers. Aberrant cardiac remodeling based on echocardiographic findings was defined as either LVCR or LVH. Discriminative performance was evaluated by the area under the receiver operating characteristic curve. RESULTS: A total of 1397 women were included, of which 139 (10%) with LVCR or LVH (mean±SD age, 43±9 years) and 1258 (90%) without LVCR or LVH (40±8 years). The final prediction model was established based on the predictors age, waist circumference, systolic blood pressure, glycated hemoglobin, antihypertensive medication use, and early onset preeclampsia (yes/no). After internal validation, the prediction model showed accurate discriminative ability with an area under the receiver operating characteristic curve of 0.702 (95% CI, 0.657-0.756). CONCLUSIONS: Based on the conventional predictors, we developed a prediction model for women who are on average 8 to 12 years postpartum. Internal validation showed accurate discriminative ability. Upon external validation, this model may aid clinicians to initiate further diagnostic testing or clinical follow-up. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02347540.

Sex Differences in the Anti-Hypertensive Effect of Calcium-Channel Blockers: A Systematic Review and Meta-Analysis.

Cardiovascular disease (CVD) is the number one cause of death worldwide, with hypertension as the leading risk factor for both sexes. As sex may affect responsiveness to antihypertensive compounds, guidelines for CVD prevention might necessitate divergence between females and males. To this end, we studied the effectiveness of calcium channel blockers (CCB) on blood pressure (BP), heart rate (HR) and cardiac function between sexes. We performed a systematic review and meta-analysis on studies on CCB from inception to May 2020. Studies had to present both baseline and follow-up measurements of the outcome variables of interest and present data in a sex-stratified manner. Mean differences were calculated using a random-effects model. In total, 38 studies with 8202 participants were used for this review. In females as compared to males, systolic BP decreased by -27.6 mmHg (95%CI -36.4; -18.8) (-17.1% (95%CI -22.5;-11.6)) versus -14.4 mmHg (95%CI -19.0; -9.9) (-9.8% (95%CI -12.9;-6.7)) (between-sex difference p < 0.01), diastolic BP decreased by -14.1 (95%CI -18.8; -9.3) (-15.2%(95%CI -20.3;-10.1)) versus -10.6 mmHg (95%CI -14.0; -7.3) (-11.2% (95%CI -14.8;-7.7)) (between-sex difference p = 0.24). HR decreased by -1.8 bpm (95%CI -2.5; -1.2) (-2.5% (95%CI -3.4; -1.6)) in females compared to no change in males (0.3 bpm (95% CI -1.2; 1.8)) (between-sex difference p = 0.01). In conclusion, CCB lowers BP in both sexes, but the observed effect is larger in females as compared to males.

The Representation of Females in Studies on Antihypertensive Medication over the Years: A Scoping Review.

BACKGROUND: The leading global risk factor for cardiovascular-disease-related morbidity and mortality is hypertension. In the past decade, attention has been paid to increase females' representation. The aim of this study is to investigate whether the representation of females and presentation of sex-stratified data in studies investigating the effect of antihypertensive drugs has increased over the past decades. METHODS: After systematically searching PubMed and Embase for studies evaluating the effect of the five major antihypertensive medication groups until May 2020, a scoping review was performed. The primary outcome was the proportion of included females. The secondary outcome was whether sex stratification was performed. RESULTS: The search resulted in 73,867 articles. After the selection progress, 2046 studies were included for further analysis. These studies included 1,348,172 adults with a mean percentage of females participating of 38.1%. Female participation in antihypertensive studies showed an increase each year by 0.2% (95% CI 0.36-0.52), p < 0.01). Only 75 (3.7%) studies performed sex stratification, and this was the highest between 2011 and 2020 (7.2%). CONCLUSION: Female participation showed a slight increase in the past decade but is still underrepresented compared to males. As data are infrequently sex-stratified, more attention is needed to possible sex-related differences in treatment effects to different antihypertensive compounds.

Exploring Sex Differences of Beta-Blockers in the Treatment of Hypertension: A Systematic Review and Meta-Analysis.

AIMS: In the prevention of cardiovascular morbidity and mortality, early recognition and adequate treatment of hypertension are of leading importance. However, the efficacy of antihypertensives may be depending on sex disparities. Our objective was to evaluate and quantify the sex-diverse effects of beta-blockers (BB) on hypertension and cardiac function. We focussed on comparing hypertensive female versus male individuals. METHODS AND RESULTS: A systematic search was performed for studies on BBs from inception to May 2020. A total of 66 studies were included that contained baseline and follow up measurements on blood pressure (BP), heart rate (HR), and cardiac function. Data also had to be stratified for sex. Mean differences were calculated using a random-effects model. In females as compared to males, BB treatment decreased systolic BP 11.1 mmHg (95% CI, -14.5; -7.8) vs. 11.1 mmHg (95% CI, -14.0; -8.2), diastolic BP 8.0 mmHg (95% CI, -10.6; -5.3) vs. 8.0 mmHg (95% CI, -10.1; -6.0), and HR 10.8 beats per minute (bpm) (95% CI, -17.4; -4.2) vs. 9.8 bpm (95% CI, -11.1; -8.4)), respectively, in both sexes' absolute and relative changes comparably. Left ventricular ejection fraction increased only in males (3.7% (95% CI, 0.6; 6.9)). Changes in left ventricular mass and cardiac output (CO) were only reported in males and changed -20.6 g (95% CI, -56.3; 15.1) and -0.1 L (95% CI, -0.5; 0.2), respectively. CONCLUSIONS: BBs comparably lowered BP and HR in both sexes. The lack of change in CO in males suggests that the reduction in BP is primarily due to a decrease in vascular resistance. Furthermore, females were underrepresented compared to males. We recommend that future research should include more females and sex-stratified data when researching the treatment effects of antihypertensives.

A Multimarker Model for Aberrant Cardiac Geometry after Preeclampsia.

One out of four women with a history of preeclampsia shows abnormal cardiac remodeling consistent with subclinical heart failure (HF) in the first decade postpartum. Since these women are susceptible for developing remote symptomatic HF, development of a model for aberrant cardiac geometry as a first screening tool after delivery, is urgently needed. In this cross-sectional study, 752 preeclamptic women were included. Cardiovascular evaluation was conducted between six months and five years postpartum including cardiac ultrasound, systolic and diastolic blood pressure (SBP and DBP), plasma volume (PV) and biomarker assessment. We developed a multimarker model using uni- and multivariable linear regression and used the regression coefficients (RC) to develop a formula and estimate the aberrant cardiac remodeling in our population. Both SBP and PV were shown to be independently correlated with relative wall thickness (RWT) and left ventricular mass index (LVMi). C-reactive protein (CRP) and uric acid were independently correlated with RWT. Fibrinogen did not relate to either LVMi or RWT. This study displays markers of abnormal cardiac remodeling in former preeclamptic women, suggesting a combination of mechanical and biochemical factors that should be involved in worrisome chamber remodeling before clinical symptoms arise.