Preterm birth and future maternal blood pressure, inflammation, and intimal-medial thickness: the CARDIA study.
ABSTRACT: Preterm birth (PTB, <37 weeks) may be a marker of endothelial dysfunction and a proinflammatory phenotype; both are risk factors for cardiovascular disease. We studied 916 women (46% black) with 1181 live births between enrollment in the Coronary Artery Risk Development in Young Adults study (age 18-30 years) and 20 years later. C-reactive protein was measured at years 7, 15, and 20. Interleukin-6 and carotid intima-media thickness, which incorporated the common carotid arteries, bifurcations, and internal carotid arteries, were measured at year 20. Blood pressure, lipids, anthropometrics, and pregnancy events were assessed at all visits. Change in risk factors and differences in inflammatory markers and intima-media thickness according to PTB were evaluated. Women with PTBs (n=226) had higher mean systolic blood pressures before pregnancy (106 versus 105 mm Hg, respectively; P=0.03). Systolic and diastolic blood pressure increased more rapidly over 20 years compared with women with term births (P<0.01 time interaction), even after removing women with self-reported hypertension in pregnancy. Women with PTB versus term births had similar mean intima-media thickness adjusted for age, body mass index, race, lifestyle, and cardiovascular risk factors. C-reactive protein and interleukin-6 did not differ according to PTB. Women with PTB, regardless of hypertension during pregnancy, had higher blood pressure after pregnancy compared with women with term births. In the United States, where rates of PTB are high and race disparities persist, PTB may identify women with higher blood pressure in the years after pregnancy.
Project description:OBJECTIVE:Preterm birth (PTB) is associated with excess maternal cardiovascular disease risk. We considered that women with PTB and placental evidence of maternal malperfusion would be particularly affected. DESIGN:Pregnancy cohort study. SETTING:Pittsburgh, PA, USA. POPULATION:Women with PTB (n = 115) and term births (n = 210) evaluated 4-12 years after pregnancy. METHODS:Cardiometabolic risk markers were compared in women with prior PTB versus term births; pre-eclampsia and growth restriction cases were excluded. Placental evidence of maternal vascular malperfusion (vasculopathy, infarct, advanced villous maturation, perivillous fibrin, intervillous fibrin deposition), acute infection/inflammation (chorioamnionitis, funisitis, deciduitus) and villitis of unknown aetiology (chronic inflammation) was used to classify PTBs. MAIN OUTCOME MEASURES:Carotid artery intima-media thickness (IMT), fasting lipids, blood pressure (BP) and inflammatory markers measured after delivery. RESULTS:Women with PTB and malperfusion lesions had higher total cholesterol (+13.5 mg/dl) and systolic BP (+4.0 mmHg) at follow up compared with women with term births, accounting for age, race, pre-pregnancy BMI, and smoking (P < 0.05). Women with PTB and malperfusion accompanied by inflammatory lesions had the most atherogenic profile after pregnancy (cholesterol +18.7, apolipoprotein B + 12.7 mg/dl; all P < 0.05), adjusted for pre-pregnancy features. Carotid IMT was higher in this group (+0.037 cm, P = 0.031) accounting for pre-pregnancy factors; differences were attenuated after adjusting for BP and atherogenic lipids at follow up (+0.027, P = 0.095). CONCLUSION:PTBs with placental malperfusion were associated with an excess maternal cardiometabolic risk burden in the decade after pregnancy. The placenta may offer insight into subtypes of PTB related to maternal cardiovascular disease. TWEETABLE ABSTRACT:Preterm births with placental malperfusion may mark women at higher cardiovascular disease risk.
Project description:Pregnancy and childbirth are associated with hemodynamic changes and vascular remodeling. It is not known whether parity is associated with later adverse vascular properties such as larger arterial diameter, wall thickness, and lower distensibility. We used baseline data from 3283 women free of cardiovascular disease aged 45 to 84 years enrolled in the population-based Multi-Ethnic Study of Atherosclerosis. Participants self-reported parity status. Ultrasound-derived carotid artery lumen diameters and brachial artery blood pressures were measured at peak-systole and end-diastole. Common carotid intima-media thickness was also measured. Regression models to determine the association of carotid distensibility coefficient, lumen diameter, and carotid intima-media thickness with parity were adjusted for age, race, height, weight, diabetes mellitus, current smoking, blood pressure medication use, and total and high-density lipoprotein cholesterol levels. The prevalence of nulliparity was 18%. In adjusted models, carotid distensibility coefficient was 0.09×10?5 Pa?1 lower (P=0.009) in parous versus nulliparous women. Among parous women, there was a nonlinear association with the greatest carotid distensibility coefficient seen in women with 2 live births and significantly lower distensibility seen in primiparas (P=0.04) or with higher parity >2 (P=0.005). No such pattern of association with parity was found for lumen diameter or carotid intima-media thickness. Parity is associated with lower carotid artery distensibility, suggesting arterial remodeling that lasts beyond childbirth. These long-term effects on the vasculature may explain the association of parity with cardiovascular events later in life.
Project description:Background The extent to which cardiovascular disease (CVD) risk factors across the menopause explain racial/ethnic differences in subclinical vascular disease in late midlife women is not well documented and was explored in a multi-ethnic cohort. Methods and Results Participants (n=1357; mean age 60 years) free of clinical CVD from the Study of Women's Health Across the Nation had common carotid artery intima-media thickness, interadventitial diameter, and carotid plaque presence assessed by ultrasonography on average 13.7 years after baseline visit. Early to late midlife time-averaged cumulative burden of traditional CVD risk factors calculated using serial measures from baseline to the ultrasound visit were generally less favorable in black and Hispanic women compared with white and Chinese women, including education and smoking status and time-averaged cumulative blood pressure, high-density lipoprotein cholesterol, and fasting insulin. Independent of these risk factors, BMI, and medications, common carotid artery intima-media thickness was thicker in black women, interadventitial diameter was wider in Chinese women, yet plaque presence was lower in black and Hispanic women compared with white women. CVD risk factor associations with subclinical vascular measures did not vary by race/ethnicity except for high-density lipoprotein cholesterol on common carotid artery intima-media thickness; an inverse association between high-density lipoprotein cholesterol and common carotid artery intima-media thickness was observed in Chinese and Hispanic but not in white or black women. Conclusions Race/ethnicity did not particularly moderate the association between traditional CVD risk factors measured across the menopause transition and late midlife subclinical vascular disease. Unmeasured socioeconomic, cultural, and nontraditional biological risk factors likely play a role in racial/ethnic differences in vascular health and merit further exploration.
Project description:OBJECTIVE:Determine associations of cardiorespiratory fitness, exercise systolic blood pressure (SBP) and heart rate recovery (HRR) following a maximal exercise test performed years preceding pregnancy with odds of preterm birth (PTB; <37 weeks' gestation) and small for gestational age (SGA; birthweight <10th percentile) delivery. DESIGN:Prospective, longitudinal. SETTING:Multi-site, observational cohort study initially consisting of 2787 black and white women aged 18-30 at baseline (1985-86) and followed for 25 years (Y25; 2010-2011). POPULATION:768 nulliparous women at baseline who reported ?1 live birth by the Y25 exam. METHODS:We used Poisson regression to determine associations of exposures with PTB/SGA. MAIN OUTCOME MEASURES:PTB and/or SGA births. RESULTS:Women with PTB (n = 143) and/or SGA (n = 88) were younger, had completed fewer years of education and were more likely to be black versus women without PTB/SGA (n = 546). Women with PTB/SGA had lower fitness (501 ± 9 versus 535 ± 6 seconds, P < 0.002) and higher submaximal SBP than women without PTB/SGA (144 ± 1 versus 142 ± 1 mmHg, P < 0.04). After adjustment, no exercise test variables were associated with PTB/SGA, though the association with HRR and submaximal SBP approached significance in the subset of women who completed the exercise test <5 years before the index birth. CONCLUSIONS:Neither fitness nor haemodynamic responses to exercise a median of 5 years preceding pregnancy, were associated with PTB/SGA. These findings indicate excess likelihood of PTB/SGA is not detectable by low fitness or exercise haemodynamic responses 5 years preceding pregnancy, but exercise testing, especially HRR and submaximal SBP, may be more useful when conducted closer to the onset of pregnancy. TWEETABLE ABSTRACT:Exercise testing conducted >5 years before pregnancy may not detect women likely to have PTB/SGA.
Project description:To analyze the relationship of cocoa intake to central and peripheral blood pressure, arterial stiffness, and carotid intima-media thickness in subjects with some cardiovascular risk factor.A cross-sectional study of 351 subjects (mean age 54.76 years, 62.4% males).Intake of cocoa and other foods using a food frequency questionnaire, central and peripheral (ambulatory and office) blood pressure, central and peripheral augmentation index, pulse wave velocity, ambulatory arterial stiffness index, carotid intima-media thickness, and ankle-brachial index.Higher pulse wave velocity and greater cardiovascular risk were found in non-cocoa consumers as compared to high consumers (p < 0.05). In a multivariate analysis, these differences disappeared after adjusting for age, gender, the presence of diabetes, systolic blood pressure and antihypertensive and lipid-lowering drug use. All other arterial stiffness measures (central and peripheral augmentation index, ambulatory arterial stiffness index, ankle-brachial index, and carotid intima-media thickness) showed no differences between the different consumption groups.In subjects with some cardiovascular risk factors, cocoa consumption does not imply improvement in the arterial stiffness values.Clinical Trials.gov Identifier: NCT01325064.
Project description:BACKGROUND: The effects of baseline and changes in blood pressure and low density lipoprotein (LDL) cholesterol on the carotid intima media thickness (IMT) have not been well documented. METHODS: A total of 2572 adults (mean age 53.8 years, 54.6% women) in a Taiwanese community undertook three blood pressure and LDL cholesterol examinations over 6 years. Latent growth curve modeling was used to investigate the effects of baseline and change in blood pressure and LDL cholesterol on IMT. RESULTS: Greater baseline LDL and blood pressure were associated with an increase in IMT (0.005 ± 0.002 mm per 1 mg/dL [p = 0.006] and 0.041 ± 0.004 mm mm Hg [p <0.0001], respectively. Change in blood pressure was associated with a significant increase in IMT (0.047 ± 0.016, P = 0.004), whilst the association between change in LDL and change in IMT was not statistically significant (0.008 ± 0.006, P = 0.20). CONCLUSIONS: Carotid IMT was associated with baseline blood pressure and LDL cholesterol, yet only changes of blood pressure, not LDL cholesterol, were related to carotid IMT during the 6-year observation.
Project description:Excess pressure integral (XSPI), a new index of surplus work performed by the left ventricle, can be calculated from blood pressure waveforms and may indicate circulatory dysfunction. We investigated whether XSPI predicted future cardiovascular events and target organ damage in treated hypertensive individuals. Radial blood pressure waveforms were acquired by tonometry in 2069 individuals (aged, 63±8 years) in the Conduit Artery Functional Evaluation (CAFE) substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Measurements of left ventricular mass index (n=862) and common carotid artery intima media thickness (n=923) were also performed. XSPI and the integral of reservoir pressure were lower in people treated with amlodipine±perindopril than in those treated with atenolol±bendroflumethiazide, although brachial systolic blood pressure was similar. A total of 134 cardiovascular events accrued during a median 3.4 years of follow-up; XSPI was a significant predictor of cardiovascular events after adjustment for age and sex, and this relationship was unaffected by adjustment for conventional cardiovascular risk factors or Framingham risk score. XSPI, central systolic blood pressure, central augmentation pressure, central pulse pressure, and integral of reservoir pressure were correlated with left ventricular mass index, but only XSPI, augmentation pressure, and central pulse pressure were associated positively with carotid artery intima media thickness. Associations between left ventricular mass index, XSPI, and integral of reservoir pressure and carotid artery intima media thickness and XSPI were unaffected by multivariable adjustment for other covariates. XSPI is a novel indicator of cardiovascular dysfunction and independently predicts cardiovascular events and targets organ damage in a prospective clinical trial.
Project description:BACKGROUND:In women with singleton pregnancies, maternal adaptation is considered a stress test for later life cardiovascular disease. The aim of this study was to assess maternal adaptation in women with twin pregnancies compared to women carrying singletons during and after pregnancy. METHODS:This was a population based prospective cohort study of 91 women with twin pregnancies and 8107 women carrying singletons. The association of twin pregnancy and maternal adaptation was examined using regression analyses. In pregnancy, we measured soluble fms-like tyrosine kinase-1 (sFLT-1), placental growth (PGF) factor, systolic (SBP) and diastolic blood pressure (DBP), and the occurrence of pre-eclampsia (PE). After pregnancy, measurements were obtained on SBP and DBP, cardiac function, retinal calibres, intima media thickness and distensibility of the common carotid artery. RESULTS:sFLT-1 and PGF concentrations were higher in early (13.4?weeks) and mid-pregnancy (20.4?weeks) in women with twin pregnancies compared to women with singleton pregnancies. Women with twin pregnancies had a different DBP pattern in pregnancy. Women with twin pregnancies were more likely to have PE (odds ratio 3.63; 95% CI [1.76 to 7.48]). Six and ten years after pregnancy, no differences in maternal adaptation were observed. CONCLUSIONS:Women with twin pregnancies show an altered adaptation during pregnancy compared to women with singleton pregnancies. This is associated with a substantially increased incidence of PE, but does not lead to persistent altered maternal adaptation years after pregnancy.
Project description:Background Assessing and optimizing cardiovascular health (CVH) early in life, such as in pregnancy, could lead to a longer lifetime spent in better CVH and reduce the risk of cardiovascular disease. This might especially benefit women with a hypertensive disorder of pregnancy (HDP) who are more likely to develop atherosclerosis and cardiovascular disease. We hypothesized that CVH in pregnancy is related to later life CVH and carotid intima-media thickness (CIMT), and that these associations differ between women with a normotensive pregnancy and women with an HDP. Methods and Results This study was conducted within the prospective population-based Generation R Study. CVH in pregnancy was based on 5 metrics (blood pressure, total-cholesterol, glucose, smoking, and body mass index). Postpartum CVH additionally included physical activity and diet scores, according to the American Heart Association classification. Postpartum CVH and CIMT were measured 10 years after pregnancy. Results were analyzed for women with a normotensive pregnancy and those with an HDP. Women with a normotensive pregnancy (n=1786) and women with an HDP (n=138) were evaluated from early pregnancy until 10 years postpartum. Better CVH in early pregnancy was associated with a smaller CIMT and better postpartum CVH in all women, especially in those with an HDP (CIMT: -9.82 μm [95% CI: -17.98, -1.67]). Conclusions Already in pregnancy, better CVH is associated with a smaller CIMT and better CVH 10 years postpartum, especially in women with an HDP. As pregnancy is an incentive for women to improve lifestyle, assessing CVH in pregnancy might help improve postpartum CVH and reduce cardiovascular disease risk.
Project description:In children, arterial alterations occur with increased intima-media thickness as well as vascular diameter enlargement. Both conditions correlate with higher cardiovascular risk in adults, and both the array and proportion of these alterations are important hemodynamic parameters. In terms of functional adaptation processes, they influence several arterial wall properties as for example the shear and tensile stress of the vessel. There are no reference values for the vascular diameter and intima-media thickness/diameter ratio of the carotid artery in children. Therefore, this study aimed to assess vascular diameter, intima-media thickness/diameter ratio and related tensile stress values in children and to further investigate the influence of sex, age, body mass index, and blood pressure. The parameters were measured with high-resolution semi-automated ultrasound. Sex- and age-dependent values were calculated with the LMS method for a cross-sectional sample of 642 healthy, non-obese children aged 8-17 years. The mean vascular diameter was 5.45?±?0.46 mm; the median intima-media thickness/diameter ratio was 0.085 (0.079-0.092); the median tensile stress was 105.4 (95.2-116.4) kPa. The vascular diameter and the tensile stress were higher, and the intima-media thickness/diameter ratio was lower in boys than in girls. In comparison to the normal weight study population the excludedobese children had a significantly higher diameter, a lower intima-media thickness/diameter ratio, and a higher tensile stress. In multiple regression analyses of diameter, intima-media thickness/diameter ratio, and tensile stress, all parameters were influenced by sex and body mass index. Furthermore, systolic and diastolic blood pressure significantly influenced the vascular diameter, and systolic blood pressure significantly influenced the intima-media thickness/diameter ratio. Conclusion: This study is the first to report values for the diameter, the intima-media thickness/diameter ratio of the carotid artery, and the related tensile stress allowing a more differentiated view of cardiovascular adaptations as it combines structural and functional vascular parameters. What is known: • Intima-media thickness and vascular diameter are related to a higher cardiovascular risk in adults • The intima-media thickness/diameter ratio gives information about hemodynamic and functional vessel adaptation What is new: • Values for vascular diameter, intima-media thickness/diameter ratio, and tensile stress of the carotid artery in children are presented in this study • Intima-media thickness as a surrogate marker for arterial health in children should be complemented by intima-media thickness/diameter ratio measurement.