Maternal cardiac dysfunction and remodeling in women with preeclampsia at term

Preeclampsia is a disease associated with significant cardiovascular morbidity during pregnancy and in later life. This study was designed to evaluate cardiac function and remodeling in preeclampsia occurring at term. This was a prospective case-control study of 50 term preeclampsia and 50 normal pregnancies assessed by echocardiography and tissue Doppler analysis. Global diastolic dysfunction was observed more frequently in preeclampsia versus control pregnancies (40% versus 14%, P = 0.007). Increased cardiac work and left ventricular mass indices suggest that left ventricular remodeling was an adaptive response to maintain myocardial contractility with preeclampsia at term. Approximately 20% of patients with preeclampsia at term have more evident myocardial damage. Diastolic dysfunction usually precedes systolic dysfunction in the evolution of ischemic or hypertensive cardiac diseases and is of prognostic value in the prediction of long-term cardiovascular morbidity. The study findings also have significant implications for the acute medical management of preeclampsia.     

Preeclampsia is associated with persistent postpartum cardiovascular impairment

Preeclampsia is associated with asymptomatic global left ventricular abnormal function and geometry during the acute phase of the disorder. These subclinical abnormalities in cardiac findings are known to be important in cardiovascular risk stratification for nonpregnant patients. Furthermore, epidemiological studies have also demonstrated a relationship between preeclampsia and cardiac morbidity and mortality later in life. The aim of this study was to evaluate the postpartum natural history and clinical significance of asymptomatic left ventricular impairment known to occur with acute preeclampsia. This was a prospective longitudinal case-control study of 64 subjects with preeclampsia and 78 matched controls. There were 3 time point assessments, pregnancy and 1 and 2 years postpartum. The assessments included a medical and family history, blood pressure profile, echocardiography, and 12-lead ECG. At 1 year postpartum, asymptomatic left ventricular moderate-severe dysfunction/hypertrophy was significantly higher in preterm preeclampsia (56%) compared with term preeclampsia (14%) or matched controls (8%; P values <0.001). The risk of developing essential hypertension within 2 years was significantly higher in both preterm preeclamptic women and those with persistent left ventricular moderate-severe abnormal function/geometry. The cardiovascular implications of preeclampsia do not end with the birth of the infant and placenta. The majority of preterm preeclamptic women have stage B asymptomatic heart failure postpartum, and 40% develop essential hypertension within 1 to 2 years after pregnancy. Women with a history of preterm preeclampsia may benefit from formal cardiovascular risk assessment in the 1 to 2 years after delivery to identify those who would benefit from targeted therapeutic intervention.     

Cardiovascular biomarker midregional proatrial natriuretic peptide during and after preeclamptic pregnancies

Preeclampsia is associated with increased risk of cardiovascular disease. Midregional proatrial natriuretic peptide (MR-proANP), a precursor of the atrial natriuretic peptide, is a biomarker for cardiovascular disease. We obtained plasma from 184 pregnant women in gestational weeks 24 to 42 (normotensive pregnancies: n=77, preeclampsia: n=107), from 25 of these women at 5 to 8 years after index pregnancy (normotensive pregnancies: n=11, preeclampsia: n=14), and from 49 normotensive, nonpregnant women and analyzed them by immunoassay for MR-proANP. To investigate potential sources, placental and decidual atrial natriuretic peptide mRNA expression levels were analyzed by quantitative real-time PCR in 21 normotensive and 23 preeclamptic pregnancies, as well as in human heart and kidney samples. For further confirmation, we measured circulating MR-proANP and performed expression studies in a transgenic rat model for preeclampsia. MR-proANP was significantly elevated in maternal plasma in preeclampsia compared with normotensive pregnancies (135 versus 56 pmol/L; P<0.001). However, 5 to 8 years after pregnancy, there was no difference (formerly preeclamptic women versus formerly normotensive in pregnancy: 53 versus 49 pmol/L; P=0.5). Our preeclamptic rat model confirmed the acute MR-proANP differences between preeclamptic and normotensive pregnancies (10.9±1.9 versus 4.3±0.3 pmol/L; P=0.05). Atrial natriuretic peptide expression was high in the heart but negligible in the uteroplacental unit in both normotensive humans and rats, whereas expression in maternal and fetal hearts in the preeclamptic rats was significantly increased, compared with controls. MR-proANP is a serviceable biomarker in preeclampsia, both in humans and a rat model, probably reflecting cardiovascular hemodynamic stress.     

Agonistic angiotensin II type 1 receptor autoantibodies in postpartum women with a history of preeclampsia

Activating angiotensin II type 1 autoantibodies (AT1-AAs) develop in women with preeclampsia and may contribute to the disorder. Insulin resistance and serum concentrations of the antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt-1) are also increased in women with preeclampsia compared with normal pregnancy. sFlt-1 and insulin resistance decrease substantially after delivery; however, significant group differences persist postpartum. Women who have had preeclampsia are at increased cardiovascular risk later in life. We measured AT1-AAs in groups of women with previous preeclampsia (n=29) and previous normal pregnancies (n=35) 18+/-9 months after the first completed pregnancy. These women had had sFlt-1, insulin resistance homeostasis model assessment score, and related cardiovascular risk factors measured. Activating antibodies were detected by the chronotropic response of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists (losartan and prazosin). AT1-AAs were detected in 17.2% of women with previous preeclampsia versus 2.9% of women with previous uncomplicated pregnancies (P<0.05). In contrast, there was no difference in the prevalence of autoantibodies against the alpha1-adrenoceptor (10% of previous preeclamptic versus 14% of previous normal pregnant). Women with activating autoantibodies had significantly increased sFlt-1, reduced free vascular endothelial growth factor, and higher insulin resistance homeostasis model assessment values compared with autoantibody-negative women. These data suggest that, as with sFlt-1 and insulin resistance, the AT1-AA does not regress completely after delivery and, secondarily, that correlations exist among these variables. The impact of AT1-AA after preeclampsia, especially in the context of cardiovascular risk, remains to be determined.     

Shared constitutional risks for maternal vascular-related pregnancy complications and future cardiovascular disease

Maternal predisposition to vascular and metabolic disease may underlie both vascular-related pregnancy complications, such as preeclampsia and intrauterine growth restriction, as well as future maternal cardiovascular disease. We aimed to substantiate this hypothesis with biochemical and anthropometric evidence by conducting an intergenerational case-control study in a Dutch isolated population including 106 women after preeclampsia or intrauterine growth restriction (median follow-up: 7.1 years) and their fathers (n=43) and mothers (n=64), as well as 106 control subjects after uncomplicated pregnancies with their fathers (n=51) and mothers (n=68). Cardiovascular risk profiles were assessed, including fasting glucose, lipids, anthropometrics, blood pressure, intima-media thickness, and metabolic syndrome. We found significantly higher fasting glucose levels, larger waist circumferences, and a 5-fold increased prevalence of hypertension in women with a history of preeclampsia as compared with control subjects (P<0.001). Likewise, their parents had higher glucose levels than control parents (P<0.05). Their mothers had larger waist circumferences and higher blood pressures (P<0.05). Also, women after pregnancies complicated by intrauterine growth restriction had higher glucose levels and increased prevalence of hypertension (P<0.01). Their fathers showed higher glucose levels as well (P<0.05). Mean carotid intima-media thickness was increased in a subset of women after preeclampsia diagnosed with chronic hypertension as compared with those without hypertension (P<0.01). Metabolic syndrome was more prevalent both in women with a history of preeclampsia and their mothers (P<0.05). We demonstrated intergenerational similarities in cardiovascular risk profiles between women after preeclampsia or intrauterine growth restriction and their parents. These findings suggest shared constitutional risks for vascular-related pregnancy complications and future cardiovascular disease.     

Pregnancy Complications and Later Development of Hypertension

Pregnancy complications such as preeclampsia and diabetes affect approximately 5 to 10 % of all pregnancies and compromise maternal and fetal health during gestation. Complications during pregnancy may also contribute to the development of hypertension and future cardiovascular risk in the mother. Moreover, fetal exposure to hypertension and diabetes during pregnancy can program hypertension and cardiovascular disease in the offspring. Transgenerational transmission of programmed cardiovascular risk highlights the importance of understanding the mechanisms that link complications during pregnancy with later hypertension in her offspring and subsequent generations. However, experimental studies are needed to investigate the cause and effect of increased blood pressure in the mother following a complicated pregnancy and provide insight into the development of preventative measures that may improve the long-term cardiovascular health of women and their offspring.     

Hypertension complicating diabetic pregnancies: pathophysiology, management, and controversies

Hypertensive disorders of pregnancy (HDP), including pre-existing hypertension, gestational hypertension, and preeclampsia, further complicate already high-risk pregnancies in women with diabetes mellitus (DM). Women with both pre-existing and gestational diabetes are at increased risk for HDP, leading to higher maternal and fetal morbidity. Further, particularly in diabetic women and women with a history of gestational diabetes, HDP significantly increases the risk for future cardiovascular events. For clinicians, women with hypertension and diabetes during pregnancy pose a management challenge. Specifically, preconception management should stress strict control of glycemia, blood pressure, and prevention of diabetic complications, specifically nephropathy, which specifically increases the risk for preeclampsia. During gestation, clinicians must be aware of potential maternal and fetal complications associated with various anti-hypertensive therapies, including known fetotoxicity of ACE inhibitors and ARBs when given in the 2nd or 3rd trimester, and the risks and benefits of expectant management versus delivery in cases of severe gestational hypertension or preeclampsia. Indeed, diabetic women must be followed closely prior to conception and throughout gestation to minimize the risk of HDP and its associated complications.     

Endothelial dysfunction: a link among preeclampsia, recurrent pregnancy loss, and future cardiovascular events?

We tested the hypothesis that endothelial dysfunction could cause placentation-related defects, persist after the complicated pregnancy, and probably cause cardiovascular disease later in life. Brachial arterial reactivity and factors related to endothelial dysfunction, such as circulating cholesterol, uric acid, nitrites, l-arginine, asymmetrical dimethylarginine, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptor-1, in women with previous healthy pregnancies (n=22), patients with severe preeclampsia (n=25), or patients with recurrent pregnancy loss (n=29), at day 10 of the luteal phase of an ovulatory cycle an average of 11 to 27 months after pregnancy were evaluated. Both groups with placentation defects had a significant decrease in endothelium-dependent dilatation, a higher rate of endothelial dysfunction, lower serum nitrites, and higher cholesterol as compared with control subjects; subjects with previous preeclampsia additionally had higher normal blood pressures and a greater parental prevalence of cardiovascular disease. Patients with recurrent pregnancy loss also demonstrated a significantly lower endothelium-independent vasodilatation. A trend to an inverse correlation was found between serum cholesterol serum and endothelial-mediated vasodilatation in the whole study population. Uric acid, l-arginine, asymmetrical dimethylarginine, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptor-1 were similar in all of the groups. We postulate that endothelial dysfunction may represent a link between preeclampsia and increased cardiovascular disease latter in life and propose that women with unexplained recurrent miscarriages are also at increased cardiovascular risk. The identification and correction of endothelial dysfunction detected during the reproductive stage on obstetric outcome and on cardiovascular diseases needs to be elucidated.     

Myocardial systolic and diastolic performance derived by 2-dimensional speckle tracking echocardiography in heart failure with normal left ventricular ejection fraction

Background- The aim of this study was to investigate the myocardial systolic and diastolic performance of the left ventricle (LV) in patients with heart failure with normal LV ejection fraction (HFNEF) through novel LV myocardial indices, which assess the systolic and diastolic function of the whole myocardium of the LV. Methods and Results- LV myocardial systolic and diastolic performance were assessed as the average value of peak systolic strain and peak early-diastolic strain rate, respectively, in longitudinal, circumferential, and radial directions from all LV segments using 2-dimensional speckle-tracking echocardiography. We studied patients with HFNEF and a control group consisting of asymptomatic subjects with LV diastolic dysfunction of similar age, sex, and LV ejection fraction. A total of 322 patients were included (92 with HFNEF and 230 with asymptomatic LV diastolic dysfunction). Myocardial systolic and diastolic LV performance were significantly lower in HFNEF (20.13±6.02% and 1.14±0.27 s(-1)) than in patients with asymptomatic LV diastolic dysfunction (25.33±6.06% and 1.37±0.33 s(-1), respectively; all P<0.0001). In addition, patients with HFNEF with low systolic and diastolic LV myocardial performance had significantly higher LV filling pressures (17.1±6.6 and 17.6±6.3 versus 12.0±5.1 and 11.7±4.7, respectively; all P<0.001) and lower cardiac output (4.8±1.0 L/min and 4.9±1.1 L/min versus 5.7±1.2 L/min and 5.8±1.1 L/min, respectively; all P<0.001) than patients with normal LV myocardial performance. In relation to these findings, the symptomatic status (ie, New York Heart Association functional class) was significantly altered in those patients with low systolic and diastolic LV myocardial performance. Conclusions- In patients with HFNEF, both systolic and diastolic LV myocardial performance are impaired, which is associated with increased LV filling pressures, decreased cardiac output, and worse New York Heart Association functional class. Therefore, the measurement of these myocardial parameters could be of great importance in HFNEF because these echocardiographic indices assess the multidirectional function of the whole myocardium of the LV, thereby allowing detection of an alteration of the global function of the LV which is associated with a worse symptomatic status in these patients.     

Prognostic Value of Cardiovascular Disease Risk Factors Measured in the First-Trimester on the Severity of Preeclampsia

Recent studies have suggested that preeclampsia and cardiovascular disease may share common mechanisms. The purpose of this prospective nested case-controlled study was to characterize a variety of cardiovascular disease risk factors measured during the first trimester of pregnancy in predicting subsequent outcomes and the severity of preeclampsia.We ascertained the severity of preeclampsia at the onset of the disease, and the presence of intrauterine growth restriction (IUGR). We compared first trimester maternal serum cardiovascular disease risk factors in preeclampsia subjects versus normal pregnancies, early-onset versus late-onset preeclampsia, and preeclampsia with IUGR versus without IUGR. To identify the prognostic value of independent predictors on the severity of preeclampsia, we calculated the area under the receiver operating characteristics curve (AUC) using logistic regression analysis.There were 134 cases of preeclampsia and 150 uncomplicated pregnancies, and preeclampsia cases were classified as early-onset (53 cases) or late-onset (81 cases), or as with IUGR (44 cases) or without IUGR (90 cases). Among the cardiovascular disease risk factors, maternal serum high-sensitive C-reactive protein (hsCRP) and homocysteine were predictors of both early-onset preeclampsia and preeclampsia with IUGR. For the detection of early onset preeclampsia or preeclampsia with IUGR, the AUC for the combination model (0.943 and 0.952, respectively) was significantly higher than with serum hsCRP or serum homocysteine only.Patients with preeclampsia can be subdivided into different severities according to time of onset and fetal weight. Cardiovascular risk factors distinguish a subgroup of these patients.     

Long-Term Cardiovascular Risks Associated With Adverse Pregnancy Outcomes: JACC Review Topic of the Week

Adverse pregnancy outcomes (APOs)—including pre-term birth, pre-eclampsia, and intrauterine growth restriction—are common interrelated disorders caused by placental dysfunction and maternal vascular abnormalities (endothelial activation, inflammation, and vasospasm) that occur in approximately 10% to 20% of pregnancies. Women who experience APOs are at increased risk for future cardiovascular disease (CVD). APOs are associated with increased risk of development of hypertension, left ventricular hypertrophy/dysfunction, vascular dysfunction, and renal dysfunction. The vascular abnormalities that are present during an APO also underlie common, difficult-to-treat forms of CVD in women as they age (e.g., cardiac microvascular dysfunction, heart failure with preserved ejection fraction), suggesting shared mechanistic pathways for APOs and CVD. Here, the authors synthesize the current information and knowledge gaps regarding the progression from APO to CVD. Understanding the risk factors for and pathogenesis of APO-related cardiovascular dysfunction is a critical unmet need that could inform efforts to prevent and more effectively treat CVD in women.     

Assessment of uterine placental circulation in thrombophilic women

Thrombophilia is associated with several complications of pregnancy including first and second trimester fetal loss, intrauterine fetal death, intrauterine growth restriction, preeclampsia, and placental abruption. Few studies have documented thrombotic lesions observed on the pathologic examination of the placenta in women with severe pregnancy complications. Moreover, a significantly higher rate of factor V Leiden and prothrombin G20210A gene mutations have been found in placentas with thrombotic events compared with normal placentas. In addition, clinical studies have been performed, using Doppler ultrasonography, to assess the uterine placental circulation in women with thrombophilia. Doppler studies of the umbilical artery in cases of intrauterine growth retardation have shown a high systolic to diastolic ratio (S/D) ratio, suggesting an increase in the resistance of the placental small vessels. When these placental vessels were examined after delivery, significant differences were found in comparison with placental vessels of normal pregnancies. Most of the Doppler studies of the umbilical and uterine arteries in pregnancies with thrombophilia were performed in women with antiphospholipid antibodies. The other pathologic conditions associated with thrombophilia and complications of pregnancy were published only recently. These few studies have demonstrated abnormal umbilical and uterine arteries blood flow in complicated pregnancies. Finally, few Doppler studies also suggest improved uterine placental circulation when women with thrombophilia received thromboprophylaxis.     

Short- and long-term changes in plasma inflammatory markers associated with preeclampsia

Preeclampsia is characterized by hypertension, dyslipidemia, and increased systemic inflammatory response and has been associated with an increased maternal risk of cardiovascular disease later in life. Low-grade chronic inflammation is a risk factor for cardiovascular disease. This study examined changes in inflammatory markers prospectively during pregnancy, the current inflammatory status of women who had a pregnancy complicated by preeclampsia 20 years previously against matched controls, and the association between inflammatory genes and risk of preeclampsia in a case (n=106) control (n=212) study. In control pregnancies (n=34), mean interleukin-10 (IL-10) levels increased 38% (P=0.012) and tumor necrosis factor-alpha (TNF-alpha) by 33% (P=0.024) between the first and third trimesters. The mean preeclampsia group IL-10 and TNF-alpha rose by 43% (P=0.013 and P=0.0065, respectively) from the first to the third trimester. In women with preeclampsia only, plasma IL-6 increased from the first to the third trimester (1.66 [2.04] to 2.94 [2.47] pg/mL; P=0.0004). Twenty years after the index pregnancy, women who had had preeclampsia demonstrated significantly higher IL-6 to IL-10 ratio (3.96 [6.07] versus 2.12 [1.89]; P=0.034) compared with a healthy index pregnancy 20 years previously, that persisted after adjustment for smoking and current body mass index. The IL-1beta (C-511T), IL-6 (G-174C), TNF-alpha (G-308A), E-selectin (S128R), intercellular adhesion molecule-1 (K469E), and C-reactive protein (C1059G) polymorphisms were not associated with risk of developing preeclampsia. In conclusion, preeclampsia is associated with short- and long-term changes in inflammatory status.     

Adverse perinatal outcomes and risk factors for preeclampsia in women with chronic hypertension: a prospective study

Prospective contemporaneous data on the outcome of pregnancies in women with chronic hypertension are sparse. Indices of maternal and perinatal morbidity and mortality were determined in 822 women with chronic hypertension with data prospectively collected and rigorously validated. The incidence of superimposed preeclampsia was 22% (n=180) with early-onset preeclampsia (相似文献   

Diastolic Stress Test for the Evaluation of Exertional Dyspnea

Recent studies have highlighted that dyspneic patients comprise a high-risk subgroup of patients referred for cardiac stress testing. Even after adjusting for the presence and degree of coronary artery disease the risk of cardiac and all-cause mortality is at least three- to fivefold higher in dyspneic patients compared to asymptomatic or those with chest pain. Stress echocardiography is uniquely positioned to characterize all potential cardiovascular etiologies of dyspnea from global and regional systolic dysfunction, myocardial ischemia to valvular heart disease, pulmonary hypertension and diastolic dysfunction. Various data point to diastolic dysfunction and associated heart failure as the major potential etiology for dyspnea as well as the likely cause of the heightened mortality risk. Doppler echocardiography at rest and with stress can now characterize the hemodynamics of diastolic dysfunction and close the loop on the comprehensive assessment of the patient who has exertional shortness of breath. This review discusses the role of the Doppler echocardiographic diastolic stress test in the evaluation of patients with cardiac dyspnea.     

Prediction of Preeclampsia-Bench to Bedside

Hypertensive disorders of pregnancy (HDP) constitute the most common medical condition seen during gestation, effecting 1 in 10 pregnancies in the USA. Traditionally, preeclampsia (PE) is defined as a new onset of hypertension and either proteinuria or end-organ dysfunction after 20 weeks of gestation in a previously normotensive woman. Preeclampsia is a potentially life-threatening condition with widespread underlying endothelial dysfunction, and accompanying inflammation, vasoconstriction, and platelet activation. Women with preeclampsia are at an increased risk for life-threatening complications and progression to eclampsia. Worldwide, 10 to 15 % of maternal deaths are from preeclampsia and related complications. Traditionally, diagnosis of preeclampsia is made based upon presence of risk factors and clinical criteria. Diagnosis is challenging in asymptomatic women early in pregnancy as well as in nulliparous women as they lack obstetric history; however, it is well known that women with previous preeclampsia have a 14.7 % risk of the condition in the second pregnancy. Prediction of those at risk and early diagnosis is crucial to enable close surveillance of high-risk women in order to improve maternal and fetal outcomes. There has been much advance in our understanding of the pathogenesis of PE and in the field of angiogenic markers. However, no one test meets the criteria for a good biomarker. A multiparametric approach appears to be optimal as we await newer systems biology approaches to give  us better insight into the pathogenesis of the disease.     

Mechanisms and Clinical Significance of Endothelial Dysfunction in High-Risk Pregnancies

The maternal cardiovascular system undergoes critical anatomic and functional adaptations to achieve a successful pregnancy outcome which, if disrupted, can result in complications that significantly affect maternal and fetal health. Complications that involve the maternal cardiovascular system are among the most common disorders of pregnancy, including gestational hypertension, preeclampsia, gestational diabetes, and impaired fetal growth. As a central feature, maternal endothelial dysfunction is hypothesized to play a predominant role in mediating the pathogenesis of these high-risk pregnancies, and as such, might proceed and precipitate the clinical presentation of these pregnancy disorders. Improving or normalizing maternal endothelial function in high-risk pregnancies might be an effective therapeutic strategy to ameliorate maternal and fetal clinical outcomes.     

Association of Preeclampsia With Myocardial Injury Among Patients Undergoing Noncardiac Surgery: The PREECLAMPSIA-VISION Study

BackgroundIn women, preeclampsia has a known association with increased long-term cardiovascular morbidity and mortality. However, it is unknown whether it is associated with increased postoperative cardiovascular morbidity and mortality in women. We aimed to determine if preeclampsia is an independent risk factor for myocardial injury after noncardiac surgery (MINS) and postoperative 30-day mortality.MethodsThis study was a large international multicentre cohort study of a representative sample of 40,004 patients recruited from August 2007 to November 2013. Participants were ≥ 45 years of age and underwent inpatient noncardiac surgery. Within this cohort, our study examined women with a history of pregnancy. Using multivariable models, we explored the association between a history of pregnancy affected by preeclampsia and our primary outcome of MINS and secondary outcome of postoperative mortality within 30 days. MINS was defined as prognostically relevant myocardial injury due to ischemia that occurred during or within 30 days after noncardiac surgery.ResultsAnalyses were restricted to the 13,902 participants with a history of pregnancy. Among these women, 976 (7.0%) had a history of preeclampsia. A history of preeclampsia was associated with an increased risk of MINS, with an adjusted hazard ratio of 1.26 (95% confidence interval 1.03-1.53; P = 0.02). Preeclampsia was not significantly associated with 30-day mortality.ConclusionsPreeclampsia is a risk factor for MINS and should be considered in the preoperative cardiovascular risk assessment of women.     

Long-term alteration in maternal blood pressure and renal function after pregnancy in normal and growth-restricted rats

Intrauterine growth restriction is associated with increased risk of adult cardiorenal diseases. Small birth weight females are more likely to experience complications during their own pregnancy, including pregnancy-induced hypertension, preeclampsia, and gestational diabetes. We determined whether the physiological demand of pregnancy predisposes growth-restricted females to cardiovascular and renal dysfunction later in life. Late gestation bilateral uterine vessel ligation was performed in Wistar-Kyoto rats. At 4 months, restricted and control female offspring were mated with normal males and delivered naturally (ex-pregnant). Regardless of maternal birth weight, at 13 months, ex-pregnant females developed elevated mean arterial pressure (indwelling tail-artery catheter; +6 mm Hg), reduced effective renal blood flow ((14)C-PAH clearance; -23%), and increased renal vascular resistance (+27%) compared with age-matched virgins. Glomerular filtration rate ((3)H-inulin clearance) was not different across groups. This adverse cardiorenal phenotype in ex-pregnant females was associated with elevated systemic (+57%) and altered intrarenal components of the renin-angiotensin system. After pregnancy at 13 months, coronary flow (Langendorff preparation) was halved in restricted females compared with controls, and together with reduced NO excretion, this may increase susceptibility to additional lifestyle challenges. Our results have implications for aging females who have been pregnant, suggesting long-term cardiovascular and renal alterations, with additional consequences for females who were small at birth.     

Alterations in left ventricular structure and function in young healthy obese women: assessment by echocardiography and tissue Doppler imaging

OBJECTIVES: This study was designed to determine the effects of obesity on left ventricular (LV) structure and function in young obese women. BACKGROUND: Severe prolonged obesity in older adults results in increased plasma volume, eccentric LV hypertrophy, and systolic and diastolic dysfunction. Obese women are at increased risk for the development of heart failure. However, the effects of the obesity on cardiac structure and function in young, otherwise-healthy women are controversial. METHODS: Fifty-one women were evaluated: 20 were obese (body mass index [BMI] > or =30 kg/m(2)) and 31 were non-obese (BMI <30 kg/m(2)). Left ventricular structure and systolic and diastolic function were assessed by two-dimensional echocardiography and tissue Doppler imaging, including the load-independent systolic myocardial velocity (Sm global) and early diastolic myocardial velocity (Em global), respectively. The effects of BMI on LV structure and function were assessed using multivariate regression analyses. RESULTS: Obese women had higher end-diastolic septal and posterior wall thickness, LV mass, and relative wall thickness than non-obese women; BMI values showed significant correlations with these variables (r = 0.58, p < 0.0001; r = 0.50, p < 0.0002; r = 0.52, p < 0.0001, and r = 0.40, p < 0.005, respectively). The Sm global and Em global were lower in obese women, suggesting systolic and diastolic function are decreased; both were negatively correlated with BMI (r = -0.43, p <. 002 and r = -0.61, p < 0.0001, respectively). Multivariate analysis showed BMI was the only independent predictor of relative wall thickness, Sm global, and Em global. CONCLUSIONS: Obesity in young otherwise-healthy women is associated with concentric LV remodeling and decreased systolic and diastolic function. These early abnormalities in LV structure and function may have important implications for explaining the myocardial dysfunction that is associated with increased cardiovascular morbidity and mortality caused by obesity.