2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2023 Statistical Update is the product of a full year's worth of effort in 2022 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. The American Heart Association strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional COVID-19 (coronavirus disease 2019) publications, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Adverse Pregnancy Outcomes and Incident Heart Failure in the Women's Health Initiative.

Importance: Some prior evidence suggests that adverse pregnancy outcomes (APOs) may be associated with heart failure (HF). Identifying unique factors associated with the risk of HF and studying HF subtypes are important next steps. Objective: To investigate the association of APOs with incident HF overall and stratified by HF subtype (preserved vs reduced ejection fraction) among postmenopausal women in the Women's Health Initiative (WHI). Design, Setting, and Participants: In 2017, an APO history survey was administered in the WHI study, a large multiethnic cohort of postmenopausal women. The associations of 5 APOs (gestational diabetes, hypertensive disorders of pregnancy [HDP], low birth weight, high birth weight, and preterm delivery) with incident adjudicated HF were analyzed. In this cohort study, the association of each APO with HF was assessed using logistic regression models and with HF subtypes using multinomial regression, adjusting for age, sociodemographic characteristics, smoking, randomization status, reproductive history, and other APOs. Data analysis was performed from January 2020 to September 2021. Exposures: APOs (gestational diabetes, HDP, low birth weight, high birth weight, and preterm delivery). Main Outcomes and Measures: All confirmed cases of women hospitalized with HF and HF subtype were adjudicated by trained physicians using standardized methods. Results: Of 10 292 women (median [IQR] age, 60 [55-64] years), 3185 (31.0%) reported 1 or more APO and 336 (3.3%) had a diagnosis of HF. Women with a history of any APO had a higher prevalence of hypertension, diabetes, coronary heart disease, or smoking. Of the APOs studied, only HDP was significantly associated with HF with a fully adjusted odds ratio (OR) of 1.75 (95% CI, 1.22-2.50), and with HF with preserved ejection fraction in fully adjusted models (OR, 2.06; 95% CI, 1.29-3.27). In mediation analyses, hypertension explained 24% (95% CI, 12%-73%), coronary heart disease 23% (95% CI, 11%-68%), and body mass index 20% (95% CI, 10%-64%) of the association between HDP and HF. Conclusions and Relevance: In this large cohort of postmenopausal women, HDP was independently associated with incident HF, particularly HF with preserved ejection fraction, and this association was mediated by subsequent hypertension, coronary heart disease, and obesity. These findings suggest that monitoring and modifying these factors early in women presenting with HDP may be associated with reduced long-term risk of HF.

Predicting Incident Heart Failure in Women With Machine Learning: The Women's Health Initiative Cohort.

BACKGROUND: Heart failure (HF) is a leading cause of cardiac morbidity among women, whose risk factors differ from those in men. We used machine-learning approaches to develop risk- prediction models for incident HF in a cohort of postmenopausal women from the Women's Health Initiative (WHI). METHODS: We used 2 machine-learning methods-Least Absolute Shrinkage and Selection Operator (LASSO) and Classification and Regression Trees (CART)-to perform variable selection on 1227 baseline WHI variables for the primary outcome of incident HF. These variables were then used to construct separate Cox proportional hazard models, and we compared these results, using receiver-operating characteristic (ROC) curve analysis, against a comparator model built using variables from the Atherosclerosis Risk in Communities (ARIC) HF prediction model. We analyzed 43,709 women who had 2222 incident HF events; median follow-up was 14.3 years. RESULTS: LASSO selected 10 predictors, and CART selected 11 predictors. The highest correlation between selected variables was 0.46. In addition to selecting well-established predictors such as age, myocardial infarction, and smoking, novel predictors included physical function, number of pregnancies, number of previous live births and age at menopause. In ROC analysis, the CART-derived model had the highest C-statistic of 0.83 (95% confidence interval [CI], 0.81-0.85), followed by LASSO 0.82 (95% CI, 0.81-0.84) and ARIC 0.73 (95% CI, 0.70-0.76). CONCLUSIONS: Machine-learning approaches can be used to develop HF risk-prediction models that can have better discrimination compared with an established HF risk model and may provide a basis for investigating novel HF predictors.

Cardiovascular Disease-Related Pregnancy Complications Are Associated with Increased Maternal Levels and Trajectories of Cardiovascular Disease Biomarkers During and After Pregnancy.

Background: Having a pregnancy complicated by hypertensive disorders of pregnancy (HDP) and/or having a small or preterm baby put a woman at risk for later cardiovascular disease (CVD). It is uncertain if higher maternal CVD risk factors (reflected by increased peripartum CVD biomarker levels) account for this risk, or if experiencing a complicated pregnancy itself increases a woman's CVD risk (reflected by an increase in biomarker trajectories from early pregnancy to postpartum). Methods: We conducted a secondary analysis of an 8-week mindful eating and stress reduction intervention in 110 pregnant women. We used mixed linear regression analysis to compare CVD biomarker levels and trajectories, between women with and without a CVD-related pregnancy complication (including HDP [gestational hypertension or preeclampsia] or having a small for gestational age [<10th percentile] or preterm [<37 weeks] baby), at three times: (1) 12-20 weeks of gestation, (2) 3 months postpartum, and (3) 9 months postpartum. CVD biomarkers studied included serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), blood pressure (BP), interleukin-6 (IL-6), tumor necrosis factor, and lipids. We adjusted for age, maternal smoking, prepregnancy BMI, BP, age × time, and BMI × time. Results: Women had a mean age of 28 years (standard deviation [SD] 6), mean prior pregnancies of 0.8 (SD 1.0), and 22 women had one or more CVD-related pregnancy complications. HOMA-IR, diastolic BP, triglyceride, high-density lipoprotein cholesterol, and IL-6 average levels, but not trajectories, differed among women with complicated versus normal pregnancy (all p values were ≤0.04). Peripartum glucose and systolic BP trajectories were statistically greater in complicated versus normal pregnancies (p values were 0.008 and 0.01, respectively). Conclusion: We conclude that the experience of a complicated pregnancy in addition to elevated CVD risk factor levels may both increase a woman's risk of future CVD. ClinicalTrials.gov Identifier: NCT01307683.

Relation of Pregnancy Loss to Risk of Cardiovascular Disease in Parous Postmenopausal Women (From the Women's Health Initiative).

Women with history of pregnancy loss (PL) have higher burden of cardiovascular disease (CVD) later in life, yet it is unclear whether this is attributable to an association with established CVD risk factors (RFs). We examined whether PL is associated with CVD RFs and biomarkers in parous postmenopausal women in the Women's Health Initiative, and whether the association between PL and CVD RFs accounted for the association between PL and incident CVD. Linear and logistic regressions were used to estimate associations between baseline history of PL and CVD RFs. Cox proportional hazards regression models were used to estimate the associations between baseline history of PL and incident CVD after adjustment for baseline RFs. Of 79,121 women, 27,272 (35%) had experienced PL. History of PL was associated with higher body mass index (p < 0.0001), hypertension (p < 0.0001), diabetes (p = 0.003), depression (p < 0.0001), and lower income (p < 0.0001), physical activity (p = 0.01), poorer diet (p < 0.0001), smoking (p < 0.0001), and alcohol use (p < 0.0001). After adjustment for CVD RFs, PL was significantly associated with incident CVD over mean follow up of 16 years (hazard ratio 1.11, 95% confidence interval 1.06 to 1.16). In conclusion, several CVD RFs are associated with PL, but they do not entirely account for the association between PL and incident CVD.

Associations between unstable housing, obstetric outcomes, and perinatal health care utilization.

BACKGROUND: While there is a growing interest in addressing social determinants of health in clinical settings, there are limited data on the relationship between unstable housing and both obstetric outcomes and health care utilization. OBJECTIVE: The objective of the study was to investigate the relationship between unstable housing, obstetric outcomes, and health care utilization after birth. STUDY DESIGN: This was a retrospective cohort study. Data were drawn from a database of liveborn neonates linked to their mothers' hospital discharge records (2007-2012) maintained by the California Office of Statewide Health Planning and Development. The analytic sample included singleton pregnancies with both maternal and infant data available, restricted to births between the gestational age of 20 and 44 weeks, who presented at a hospital that documented at least 1 woman as having unstable housing using the International Classification of Diseases, ninth edition, codes (n = 2,898,035). Infants with chromosomal abnormalities and major birth defects were excluded. Women with unstable housing (lack of housing or inadequate housing) were identified using International Classification of Diseases, ninth edition, codes from clinical records. Outcomes of interest included preterm birth (<37 weeks' gestational age), early term birth (37-38 weeks gestational age), preterm labor, preeclampsia, chorioamnionitis, small for gestational age, long birth hospitalization length of stay after delivery (vaginal birth, >2 days; cesarean delivery, >4 days), emergency department visit within 3 months and 1 year after delivery, and readmission within 3 months and 1 year after delivery. We used exact propensity score matching without replacement to select a reference population to compare with the sample of women with unstable housing using a one-to-one ratio, matching for maternal age, race/ethnicity, parity, prior preterm birth, body mass index, tobacco use during pregnancy, drug/alcohol abuse during pregnancy, hypertension, diabetes, mental health condition during pregnancy, adequacy of prenatal care, education, and type of hospital. Odds of an adverse obstetric outcome were estimated using logistic regression. RESULTS: Of 2794 women with unstable housing identified, 83.0% (n = 2318) had an exact propensity score-matched control. Women with an unstable housing code had higher odds of preterm birth (odds ratio, 1.2, 95% confidence interval, 1.0-1.4, P < .05), preterm labor (odds ratio, 1.4, 95% confidence interval, 1.2-1.6, P < .001), long length of stay (odds ratio, 1.6, 95% confidence interval, 1.4-1.8, P < .001), emergency department visits within 3 months (odds ratio, 2.4, 95% confidence interval, 2.1-2.8, P < .001) and 1 year after birth (odds ratio, 2.7, 95% confidence interval, 2.4-3.0, P < .001), and readmission within 3 months (odds ratio, 2.7, 95% confidence interval, 2.2-3.4, P < .0014) and 1 year after birth (odds ratio, 2.6, 95% confidence interval, 2.2-3.0, P < .001). CONCLUSION: Unstable housing documentation is associated with adverse obstetric outcomes and high health care utilization. Housing and supplemental income for pregnant women should be explored as a potential intervention to prevent preterm birth and prevent increased health care utilization.

HIV and coronary artery calcium score: comparison of the Hawaii Aging with HIV Cardiovascular Study and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts.

OBJECTIVES: To determine the association of HIV, immunologic, and inflammatory factors on coronary artery calcium (CAC), a marker of subclinical atherosclerosis. METHODS: Cross-sectional study comparing baseline data of males from Hawaii Aging with HIV - Cardiovascular Study (HAHCS) with the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. The cohorts were pooled to determine effects of HIV on CAC and explore immunologic and inflammatory factors that may explain development of CAC in HIV. Multivariable regression models compared CAC prevalence in HAHCS with MESA adjusting for coronary heart disease (CHD) risk profiles. RESULTS: We studied 100 men from HAHCS and 2733 men from MESA. Positive CAC was seen in 58% HAHCS participants and 57% MESA participants. Mean CAC was 260.8 in HAHCS and 306.5 in MESA. Using relative risk (RR) regression, HAHCS participants had a greater risk (RR = 1.20, P < 0.05) of having positive CAC than MESA when adjusting for age, smoking status, diabetes, antihypertensive therapy, BMI, systolic blood pressure, total cholesterol, and HDL cholesterol. Among participants with positive CAC, HIV infection was not associated with larger amounts of CAC. Among HAHCS participants, current HIV viral load, CD4, length of HIV, interleukin 6 (IL-6), fibrinogen, C-reactive protein (CRP), and D-dimer were not associated with the presence or amount of CAC. DISCUSSION: HIV was independently associated with a positive CAC in men with increased likelihood occurring between 45 and 50 years of age. Current HIV viral load, CD4 count, length of HIV, and inflammatory markers were unrelated to either presence or amount of CAC.

Lipoprotein concentration, particle number, size and cholesterol efflux capacity are associated with mitochondrial oxidative stress and function in an HIV positive cohort.

BACKGROUND: Association of lipoprotein particle size/number and HDL function with mitochondrial oxidative stress and function may underlie the excess cardiovascular (CVD) risk in HIV. METHODS AND RESULTS: Among HIV infected individuals on stable highly active antiretroviral therapy, we related standard and novel lipid measures [plasma total cholesterol, triglycerides, HDL-C, LDL-C, lipoprotein particle (-P) subclass size and number and HDL function (via cholesterol-efflux capacity)] with oxidative stress [peripheral blood mononuclear cell's mitochondrial-specific 8-oxo-deoxyguanine (8-oxo-dG)] and function markers [oxidative phosphorylation (OXPHOS) NADH dehydrogenase (Complex I) and cytochrome c oxidase (Complex IV) enzyme activities]. Multivariable-adjusted logistic and linear regression analyses were employed adjusting for age, gender, CD4 nadir, viral load, smoking, diabetes, HOMA-IR, hypertension and lipid medications. Among 150 HIV-infected persons (mean age 52 years, 12% women, median CD4 count 524 cell/mm3), low HDL-C and high total cholesterol/HDL-C ratio were related to PBMC 8-oxo-deoxyguanine (p = 0.01 and 0.02 respectively). Large HDL-P and HDL-P size were inversely related to PBMC 8-oxo-deoxyguanine (p = 0.04). Small LDL-P (p = 0.01) and total LDL-P (p = 0.01) were related to decreased OXPHOS Complex I activity. LDL-P was related to decreased OXPHOS Complex IV activity (p = 0.02). Cholesterol efflux capacity was associated with increased OXPHOS Complex IV activity. CONCLUSIONS: HDL concentration and particle size and number are related to decreased PBMC mitochondrial oxidative stress whereas HDL function is positively related to mitochondrial oxidative function. The association we find between atherogenic lipoprotein profile and increased oxidative stress and function suggests these pathways may be important in the pathogenesis of cardiometabolic disease in HIV disease.

Reduced CD14 expression on classical monocytes and vascular endothelial adhesion markers independently associate with carotid artery intima media thickness in chronically HIV-1 infected adults on virologically suppressive anti-retroviral therapy.

HIV infection causes systemic immune inflammation, and increases the risk for cardiovascular (CVD) disease even among those on virologically suppressive anti-retroviral treatment (ART). We performed a biostatistical analysis and screen of candidate cellular and plasma biomarkers for association with carotid artery intima-media thickness (CIMT), independent of traditional CVD risk factors such as age, gender, systolic blood pressure (SBP), lipid levels, smoking and diabetes. We conducted a multi-stage analysis based on a cross-sectional study of CVD risk in HIV-infected subjects age >45 years on ART for >6 months. The goal of this analysis was to identify candidate cellular and plasma biomarkers of CIMT in HIV-1 infected adults. We further sought to determine if these candidate biomarkers were independent of traditional CVD risk factors previously identified in HIV negative adults. High-resolution B-mode ultrasound images of the right common carotid common artery (CCA) were obtained. Plasma soluble inflammatory mediators, cytokines and chemokines were detected. Monocytes were defined by CD14/CD16 expression, and CD8+ T-cell activation by CD38/HLA-DR expression. Subjects were a median of 49.5 years old, 87% male, had a CIMT of 0.73 mm, FRS of 6%, a median viral load of 48 copies/mL, and CD4+ T cell count of 479 cells/µL. Soluble VCAM-1, and expansion of CD14dimCD16- monocytes each associated with higher CIMT independently of age and SBP. These factors are distinct components of a shared atherogenic process; 1) vascular endothelial molecular expression and 2) vascular monocytes that enter into the vascular endothelium and promote atherosclerotic plaque.

Feasibility and potential role of ferumoxytol-enhanced neuroimaging in HIV-associated neurocognitive disorder.

We assessed ferumoxytol-enhanced brain MRI to identify monocyte/macrophage accumulation in HIV-associated neurocognitive disorder (HAND). Four HIV-infected subjects with undetectable HIV RNA levels on antiretroviral therapy, HIV DNA level in CD14+ cells ≥10 copies/10(6) cells, and cognitive impairment underwent ferumoxytol-enhanced brain MRI. On post-ferumoxytol susceptibility-weighted images, all HIV-infected subjects demonstrated a diffuse "tram track" appearance in the perivascular regions of cortical and deep white matter vessels suggesting ferumoxytol uptake in monocytes/macrophages. This finding was not present in an HIV-seronegative control. While ferumoxytol may have potential as an imaging biomarker for monocyte/macrophage accumulation in patients with HAND, future study is needed.

IL-1Β enriched monocytes mount massive IL-6 responses to common inflammatory triggers among chronically HIV-1 infected adults on stable anti-retroviral therapy at risk for cardiovascular disease.

Chronic infection by HIV increases the risk of cardiovascular disease (CVD) despite effective antiretroviral therapy (ART). The mechanisms linking HIV to CVD have yet to be fully elucidated. High plasma levels of the pro-inflammatory cytokine IL-6, which may be triggered by IL-1ß, is a biomarker of CVD risk in HIV-negative adults, and of all-cause mortality in HIV disease. Monocytes play a pivotal role in atherosclerosis, and may be major mediators of HIV-associated inflammation. We therefore hypothesized that monocytes from HIV-infected adults would display high inflammatory responses. Employing a 10-color flow cytometry intracellular cytokine staining assay, we directly assessed cytokine and chemokine responses of monocytes from the cryopreserved peripheral blood of 33 chronically HIV-1 infected subjects. Participants were 45 years or older, on virologically suppressive ART and at risk for CVD. This group was compared to 14 HIV-negative subjects matched for age and gender, with similar CVD risk. We simultaneously detected intracellular expression of IL-1ß, IL-6, IL-8 and TNF in blood monocytes in the basal state and after stimulation by triggers commonly found in the blood of treated, chronically HIV-infected subjects: lipopolysaccharide (LPS) and oxidized low-density lipoprotein (oxLDL). In the absence of stimulation, monocytes from treated HIV-infected subjects displayed a high frequency of cells producing IL-1ß (median 19.5%), compared to low levels in HIV-uninfected persons (0.9% p<0.0001). IL-8, which is induced by IL-1ß, was also highly expressed in the HIV-infected group in the absence of stimulation, 43.7% compared to 1.9% in HIV-uninfected subjects, p<0.0001. Strikingly, high basal expression of IL-1ß by monocytes predicted high IL-6 levels in the plasma, and high monocyte IL-6 responses in HIV-infected subjects. Hyper-inflammatory IL-1ß enriched monocytes may be a major source of IL-6 production and systemic inflammation in HIV-infected adults, and may contribute to the risk for all-cause mortality and cardiovascular disease in treated HIV infection.

Albuminuria as a marker of cardiovascular risk in HIV-infected individuals receiving stable antiretroviral therapy.

UNLABELLED: Albuminuria (urinary excretion of more than 30 milligram of albumin per gram of creatinine) serves as an indicator of microvascular injury, which has been associated with atherosclerosis and cardiovascular disease in HIV-seronegative individuals. Albuminuria has been reported to be prevalent among HIV-seropositive individuals, however, the relationship between albuminuria and risk for cardiovascular disease in this population has not been well-studied. We examined the relationships between albuminuria and parameters of atherosclerosis including carotid intima-media thickness and traditional cardiovascular risk assessment among HIV-seropositive individuals receiving stable antiretroviral therapy. We utilized a cross-sectional baseline data from the Hawai'i Aging with HIV-Cardiovascular Study cohort. RESULTS: Data was available on 111 HIV-infected patients (median age of 52 (Q1,Q3: 46, 57), male 86%; diabetes 6%; hypertension 33%; dyslipidemia 50%; median CD4 count of 489 cells/mm(3) (341, 638); HIV RNA PCR < 48 copies/ml of 85%). Eighteen subjects (16.2%) had microalbuminuria, and two subjects (1.8%) had macroalbuminuria. Albuminuria was significantly associated with increased Framingham Risk Score (P=.002), insulin resistance by HOMA-IR (P=.02), diastolic blood pressure (P=.01), and carotid intima-media thickness (P =.04). The correlation between the amount of albuminuria and carotid intima-media thickness remained significant even after adjusting for age, gender, ethnicity, current smoking status, diabetes mellitus, diastolic blood pressure, fasting insulin level, CD4 count, and HIV-RNA viral load. CONCLUSION: Albuminuria is prevalent among HIV-infected patients receiving stable antiretroviral therapy. It is significantly related to previously defined markers of cardiovascular disease and metabolic syndrome among HIV-infected patients receiving stable antiretroviral therapy.

Pregnancy Complications and the Risk of Metabolic Syndrome for the Offspring.

Metabolic syndrome is a growing problem globally, and is a contributor to non-communicable diseases such as type II diabetes and cardiovascular disease. The risk of developing specific components of the metabolic syndrome such as obesity, hyperlipidemia, hypertension, and elevated fasting blood sugar has been largely attributed to environmental stressors including poor nutrition, lack of exercise, and smoking. However, large epidemiologic cohorts and experimental animal models support the "developmental origins of adult disease" hypothesis, which posits that a significant portion of the risk for adult metabolic conditions is determined by exposures occurring in the perinatal period. Maternal obesity and the rate of complications during pregnancy such as preterm birth, preeclampsia, and gestational diabetes continue to rise. As our ability to reduce perinatal morbidity and mortality improves the long-term metabolic consequences remain uncertain, pointing to the need for further research in this area.

Association of number of live births with left ventricular structure and function. The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Pregnancy is associated with marked maternal cardiovascular/hemodynamic changes. A greater number of pregnancies may be associated with long-term subclinical changes in left ventricular (LV) remodeling. METHODS: Among 2,234 white, black, Hispanic, and Chinese women (mean age 62 years) in the MESA, we used linear regression to relate live births and cardiac magnetic resonance imaging LV measures. Covariates included age, ethnicity, height, income, education, birth country, smoking, menopause, and oral contraceptive duration. Models were additionally adjusted for potential mediators: systolic blood pressure, antihypertensive use, total/high-density lipoprotein cholesterol, triglycerides, diabetes, and body mass index. We performed sensitivity analyses excluding 763 women in the lowest socioeconomic group: annual income <$25,000 and lower high school level of education. RESULTS: With each live birth, LV mass increased 1.26 g; LV end-diastolic volume, 0.74 mL; and LV end-systolic volume, 0.45 mL; LV ejection fraction decreased 0.18% (P trend <0.05). Changes were most notable for the category of women with ≥5 pregnancies. Upon adjustment for potential biologic mediators, live births remained positively associated with LV mass and end-systolic volume. Live births remained significantly associated with LV end-systolic, end-diastolic volumes, and LV mass (P trend ≤0.02) after excluding women in the lowest socioeconomic group. CONCLUSIONS: Number of live births is associated with key LV structural and functional measures in middle to older ages, even after adjustment for sociodemographic factors and cardiovascular disease risk factors. Hemodynamic changes during pregnancy may be associated with cardiac structure/function beyond childbearing years.

Subfertility and risk of later life maternal cardiovascular disease.

BACKGROUND: Subfertility shares common pathways with cardiovascular disease (CVD), including polycystic ovarian syndrome, obesity and thyroid disorders. Women with prior 0-1 pregnancies are at an increased risk of incident CVD when compared with women with two pregnancies. It is uncertain whether history of subfertility among women eventually giving birth is a risk factor for CVD. METHODS: Among Swedish women with self-reported data on subfertility in the Swedish Medical Birth Register (n = 863 324), we used Cox proportional hazards models to relate a history of subfertility to CVD risk after adjustment for age, birth year, highest income, education, birth country, hypertension, diabetes, preterm birth, small for gestational age (SGA), smoking and for BMI in separate models. In additional analyses, we excluded women with: (i) pregnancy-related or non-pregnancy-related hypertension and/or diabetes; and (ii) preterm births and/or SGA babies. RESULTS: Among nulliparous women eventually having a childbirth (between 1983 and 2005, the median follow-up time 11.9; 0-23 years and 9 906 621 person-years of follow-up), there was an increased risk of CVD among women reporting ≥ 5 years of subfertility versus 0 years (hazard ratio 1.19, 95% confidence interval 1.02-1.39). There were not significantly elevated CVD risks for women with 1-2 or 3-4 years of subfertility versus 0 years. Accounting for BMI did not change results. Excluding women with hypertension and/or diabetes attenuated associations, whereas exclusion of women with preterm and/or SGA births did not change findings. CONCLUSIONS Subfertility among women eventually having a childbirth is a risk factor for CVD even upon accounting for cardiovascular risk factors and adverse pregnancy outcomes. Future studies should explore the mechanisms underlying this association.

Birth characteristics and subsequent risks of maternal cardiovascular disease: effects of gestational age and fetal growth.

BACKGROUND: Prior studies showing an inverse relationship between low birth weight in offspring and maternal risks of cardiovascular diseases (CVD) are limited by lack of information on gestational age and/or insufficient adjustment for confounders. METHODS AND RESULTS: In a nationwide Swedish study, we included information on 923 686 women and their first singleton births between 1983 and 2005. Cox proportional hazards models were used to study associations between gestational length, fetal growth, and maternal incident hospitalization or death from CVD (coronary heart disease, cerebrovascular events, and heart failure). Multivariable adjusted models accounted for birth year, income, education, country of birth, smoking, diabetes mellitus, hypertension, and preeclampsia. The risk of maternal CVD increased with decreasing gestational age whereas the risk increase related to fetal growth appeared to be restricted to very small-for-gestational-age (SGA) infants. Compared with mothers of non-SGA infants born at term, the hazard ratio of CVD ranged from 1.39 (95% confidence interval 1.22-1.58) to 2.57 (95% confidence interval 1.97-3.34) among mothers to moderately and very preterm infants, respectively. There was a significant interaction between preterm birth and fetal growth with respect to mothers' risk of CVD (P<0.001). Among mothers to very SGA infants, the hazard ratio of CVD ranged from 1.38 (95% confidence interval 1.15-1.65) to 3.40 (95% confidence interval 2.26-5.11) in mothers to term and very preterm infants, respectively. CONCLUSIONS: Delivery of a preterm or SGA infant is associated with later life maternal hospitalization or death from CVD even after accounting for socioeconomic factors, smoking, and pregnancy-related complications.

Clinical correlates and heritability of cystatin C (from the Framingham Offspring Study).

Cystatin C (CysC) is associated with cardiovascular disease (CVD) and chronic kidney disease (CKD). We examined the clinical correlates and heritability of CysC and determined if associations between CVD risk factors and CysC differed by CKD status. Among Framingham Heart Study offspring (examined from 1998-2001, n = 3,241, mean age 61 years, 54% women), the 95(th) percentile cut-point was developed for CysC in a healthy subset (n = 779) after excluding participants with diabetes, hypertension, low high-density lipoproteins, obesity, smoking, high triglycerides, prevalent CVD, and CKD (as defined by glomerular filtration rate <60 mL/min per 1.73 m(2)). Multivariable logistic regression was used to evaluate the association between CVD risk factors and high CysC (CysC > or =95(th) percentile cut-point). In a family-based subset (n = 1,188), we estimated CysC heritability using the variance-components method. The cut-point for high CysC was 1.07 mg/L. Age, hypertension treatment, low diastolic blood pressure, body mass index, low high-density lipoprotein cholesterol, and smoking were associated with high CysC in multivariable models. These factors and estimated glomerular filtration rate (egFR) explained 39.2% of CysC variability (R(2)). Excluding CKD did not materially change associations. Multivariable-adjusted heritability for CysC was 0.35 (p <0.001). In conclusion, high CysC is associated with CVD risk factors even in the absence of CKD. The strong associations between CysC and CVD risk factors may partially explain why CysC is a strong predictor of incident CVD.

Indexes of kidney function and coronary artery and abdominal aortic calcium (from the Framingham Offspring Study).

It is uncertain whether moderate chronic kidney disease (CKD) or measures of kidney function are associated with subclinical atherosclerosis as represented by coronary artery calcium (CAC) or abdominal aortic calcium (AAC). We used logistic and linear regression analyses to relate CKD (glomerular filtration rate <60 ml/min/1.73 m(2)), cystatin C (cysC), and microalbuminuria (MA) with CAC and AAC obtained using multidetector computed tomography in Framingham Heart Study Offspring participants (mean age 59 years, 55.3% women). Increased CAC and AAC were defined as > or =90th percentile age- and gender-specific cutpoints based on a healthy referent sample. Major cardiovascular disease risk factors were accounted for in multivariable models. Of 1,179 participants, 1,174 had AAC measurements and 1,147 had CAC measurements, 6.3% had CKD, and 8.3% had MA. CKD was not associated with CAC (multivariable-adjusted odds ratio [OR] for CKD 1.18, 95% confidence interval 0.59 to 2.36, p = 0.63) or AAC (multivariable-adjusted OR for CKD 1.11, 95% confidence interval 0.61 to 2.04, p = 0.73). CysC was associated with CAC in age- and gender-adjusted but not in multivariable models (age- and gender-adjusted OR for log cysC per SD increment and CAC 1.19, 95% confidence interval 1.01 to 1.41, p = 0.04; multivariable-adjusted OR 1.14, 95% confidence interval 0.95 to 1.38, p = 0.15). MA was not associated with CAC (OR 0.81, 95% confidence interval 0.41 to 1.61, p = 0.54). Neither cysC nor MA was significantly associated with AAC in age- and gender- or multivariable-adjusted models. In conclusion, CKD, cysC, and MA are not associated with CAC or AAC when accounting for cardiovascular disease risk factors.