Coutinho, Thais

Thais Coutinho, 2011 Finalist and Presenting Author

AbstractBackgroundHypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity and mortality, and their association with increased cardiovascular disease (CVD) risk represents a major public health concern. However, assessing CVD risk in women with a history of these conditions presents unique challenges, especially when studies are carried out using routinely collected data.ObjectivesTo summarise and describe key challenges related to the design and conduct of administrative studies assessing CVD risk in women with a history of HDP and provide concrete recommendations for addressing them in future research.MethodsThis is a methodological guidance paper.ResultsSeveral conceptual and methodological factors related to the data‐generating mechanism and study conceptualisation, design/data management and analysis, as well as the interpretation and reporting of study findings should be considered and addressed when designing and carrying out administrative studies on this topic. Researchers should develop an a priori conceptual framework within which the research question is articulated, important study variables are identified and their interrelationships are carefully considered.ConclusionsTo advance our understanding of CVD risk in women with a history of HDP, future studies should carefully consider and address the conceptual and methodological considerations outlined in this guidance paper. In highlighting these challenges, and providing specific recommendations for how to address them, our goal is to improve the quality of research carried out on this topic.

Background Women with preeclampsia have a higher risk of cardiovascular disease. This is partly explained by the worse arterial health after preeclampsia. Central obesity (CO) is a risk factor for both preeclampsia and cardiovascular disease. Whether CO contributes to further worsening of arterial health after preeclampsia remains unclear. Our objective was to evaluate the effect of CO and previous preeclampsia on arterial hemodynamics. Methods and Results We studied 40 women with previous preeclampsia (<6 years) and 40 age‐matched controls with previous normotensive pregnancy in the same timeframe. We estimated arterial hemodynamics with validated techniques combining applanation tonometry and echocardiography. CO was defined as a waist‐to‐hip ratio ≥0.85. Differences in arterial hemodynamics across the 3 groups (preeclampsia with CO, preeclampsia without CO, and controls) were assessed with multivariable linear regression models adjusted for potential confounders. Twenty‐six (65%) of the participants with preeclampsia had CO compared with 18 (45%) controls. Mean waist‐to‐hip ratio in patients with preeclampsia with CO, those with preeclampsia and no CO, and controls was 0.94±0.05, 0.80±0.04, and 0.83±0.07, respectively. In multivariable analyses, women with preeclampsia and CO had higher central blood pressure, arterial stiffness (carotid‐femoral pulse wave velocity), steady arterial load (systemic vascular resistance), and wave reflections (reflected pressure wave amplitude, augmentation index) compared with controls ( P <0.05 for each). Fewer hemodynamic domains were altered in the preeclampsia with no CO group, with higher central diastolic blood pressure, systemic vascular resistance, and wave reflections than controls ( P <0.05). Conclusions Women with previous preeclampsia who also experience CO have the greatest alterations in arterial health and hemodynamics. Patients with preeclampsia with CO may represent a higher‐risk subgroup who could be targeted for risk stratification and primary prevention of cardiovascular disease.

Abstract BACKGROUND Preeclampsia (PE) is associated with increased cardiovascular risk. Recent data have shown worse left ventricular remodeling and diastolic function in women with PE and persistent hypertension (HTN). We performed a comprehensive arterial hemodynamic assessment to evaluate the contribution of persistent HTN on arterial health after PE. METHODS We recruited 40 women with PE history and 40 age-matched controls (6 months to 6 years postpartum). We evaluated arterial hemodynamics with validated techniques combining applanation tonometry and transthoracic echocardiography, comparing three groups: previous PE with persistent HTN (PE-HTN), previous PE with normalized blood pressure (PE-noHTN) and controls, using multivariable linear regression adjusted for age, body surface area, heart rate, diabetes, smoking history, creatinine, and gravidity. RESULTS Eight (20%) of the post-PE women had persistent HTN. Mean age was 35.8 ± 3.9 years, median number of pregnancies was 2 (range 1–7), and time since last pregnancy 2.1 (range 0.5–5.7) years (not different between groups, P &gt; 0.05). Compared to controls and to PE-noHTN, PE-HTN had higher aortic stiffness, wave reflections, pulsatile, and steady arterial load (P &lt; 0.05 for each). Among PE-noHTN, aortic stiffness, wave reflections and steady arterial load were worse than controls (P &lt; 0.05 for each), with smaller effect sizes. CONCLUSIONS This is the most comprehensive assessment of arterial hemodynamics and first to demonstrate the contribution of persistent HTN on worse arterial health following PE. Since measures of arterial health are associated with cardiovascular events in the population, the combination of previous PE and chronic HTN may represent a higher risk subgroup who could benefit from targeted prevention strategies.

Left ventricular (LV) hypertrophy, a marker for adverse cardiovascular events, is more common in blacks than in non-Hispanic whites. Mechanisms leading to LV hypertrophy and mediating its clinical sequelae in blacks are not fully understood. We investigated the associations of 39 candidate biomarkers in distinct biological pathways with LV mass and geometry in blacks. Participants included 1193 blacks (63±9 years of age; 72% women; 78% hypertensive) belonging to hypertensive sibships. LV mass was measured by transthoracic echocardiography and indexed to height. 2.7 LV geometry was categorized as normal, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Generalized estimating equations were used to assess associations of the 39 biomarkers with LV mass index after adjustment for age, sex, and conventional risk factors. After adjustment for potential confounders, log-transformed levels of the following biomarkers were independently associated with LV mass index: N-terminal pro-brain natriuretic peptide (β±SE=0.07±0.01 pg/mL; P <0.0001), mid-regional pro-atrial natriuretic peptide (β±SE=0.08±0.02 pmol/L; P <0.0001), mid-regional pro-adrenomedullin (β±SE=0.09±0.03 nmol/L; P =0.0006), C-terminal pro-endothelin (β± SE=0.05±0.02 pmol/L; P =0.0009), and osteoprotegerin (β±SE=0.07±0.02 pg/mL; P =0.0005) (β is for 1 log increase in biomarker level). The associations of these biomarkers with LV mass index were mainly due to their association with eccentric hypertrophy. Higher circulating levels of natriuretic peptides, adrenomedullin, endothelin, and osteoprotegerin were associated with increased LV mass index, providing insights into the pathophysiology of LV hypertrophy in blacks.

Functional performance influences quality of life in individuals with peripheral artery disease (PAD) and is also a powerful prognostic marker in these patients. The pathophysiology of impaired functional performance in patients with PAD is incompletely understood. The severity of atherosclerotic burden, non-invasively assessed by the ankle—brachial index (ABI), does not reliably predict the degree of functional impairment observed in PAD patients. We review associations of measures of arterial function (arterial stiffness and endothelial dysfunction) with functional performance in PAD patients, and also review potential therapies for arterial stiffness and endothelial dysfunction that could improve functional performance in PAD. Recent studies suggest that measures of arterial function, such as arterial stiffness and endothelial function, are associated with exercise performance in the setting of PAD. These studies have provided new insights into (1) the pathophysiology of functional impairment in PAD, (2) mechanisms of strategies known to be effective such as walking programs, and (3) potential new therapeutic interventions for improving functional performance. Thus, therapies aimed at arterial ‘de-stiffening’ and improving endothelial function (such as aerobic exercise, statins and angiotensin-converting enzyme inhibitors) may improve functional performance in patients with PAD; however, further investigations are needed.