Cardiovascular Disease In Later Life Research Articles

Abstract 62: Association of Cardiovascular Health Trajectories Through Young Adulthood With Later-Life Incident Cardiovascular Disease and Mortality: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Introduction: Associations of mid-life cardiovascular health (CVH) and incident cardiovascular disease (CVD) are well-studied. Less is known about patterns of young adulthood (YA) CVH, including its changes, and associations with later-life CVD outcomes. Methods: CVH was defined by Life’s Essential 8 (LE8) score. First, we used latent class modeling (SAS Proc Traj) to determine trajectories of continuous CVH scores (0-100) for CARDIA participants with ≥3 CVH measurements in YA (from year [Y]0, mean age 25, to Y20, mean age 45). Second, we examined direction and magnitude of change in CVH status (low, moderate, or high) between 2 CVH measurements (at Y0 and Y20), comparing participants with increased, decreased, or stable CVH status. Outcomes included incident CVD (MI, heart failure, stroke, CVD death) after Y20. Cox proportional hazards regression was used to estimate HRs for associations of YA CVH patterns with incident CVD. Results: There were 4,257 participants in YA (44% female, 48% Black) included. In the trajectory analysis, we identified four distinct CVH trajectory groups ( Figure 1A ): compared to the Persistently-High CVH group, the Moderate-Low-Declining and Moderate-Declining CVH trajectory groups had substantially higher hazards for incident CVD ( Figure 1B ). In the CVH status change analysis (N=2,884; Figure 1B ), compared to Stable High CVH in YA, Stable Low CVH had a 19-fold higher risk for incident CVD, and both increasing and decreasing CVH status in YA had greater risk for incident CVD as well. Conclusions: Trajectories of declining moderate and low CVH in YA had substantially higher risk for later-life incident CVD events. Those with decreasing CVH and those who started with lower CVH and improved it through YA, were also at higher risk. These data suggest that early life CVH and maintaining high CVH through YA are both important for prevention of later-life CVD.

Abnormal Lipid Profile Level in Neonates and Possible Development of Atherosclerosis in Adulthood: Mini Review

The lipid profile during the neonatal period plays a pivotal role in determining the future risk of atherosclerosis and cardiovascular diseases in adulthood. Abnormal lipid levels in neonates have been associated with an increased propensity for the development of atherosclerosis later in life. This review aims to explore the significance of abnormal lipid profiles in neonates and their potential implications for the development of atherosclerosis in adulthood. The discussion encompasses the mechanisms underlying lipid metabolism in early life, the impact of various factors on lipid levels in neonates, and the long-term consequences of abnormal lipid profiles. Understanding the relationship between neonatal lipid profiles and the risk of atherosclerosis in adulthood is crucial for developing preventive strategies and interventions aimed at reducing the burden of cardiovascular diseases in later life. This review synthesizes idea from existing literature to provide insights into the importance of early lipid assessment and its implications for long-term cardiovascular health. Keywords: Abnormal Lipid Profile, Neonates, Atherosclerosis, Cardiovascular Risk, Lipid Metabolism, Early Life, Long-term Health, Preventive Strategies, Cardiovascular Disease

Genomic variation associated with cardiovascular disease progression following preeclampsia: a systematic review.

Women with a history of preeclampsia (PE) have been shown to have up to five times the risk of developing later-life cardiovascular disease (CVD). While PE and CVD are known to share clinical and molecular characteristics, there are limited studies investigating their shared genomics (genetics, epigenetics or transcriptomics) variation over time. Therefore, we sought to systematically review the literature to identify longitudinal studies focused on the genomic progression to CVD following PE. A literature search of primary sources through PubMed, Scopus, Web of Science and Embase via OVID was performed. Studies published from January 1, 1980, to July 28, 2023, that investigated genomics in PE and CVD were eligible for inclusion. Included studies were screened based on Cochrane systematic review guidelines in conjunction with the PRISMA 2020 checklist. Eligible articles were further assessed for quality using the Newcastle-Ottawa scale. A total of 9,231 articles were screened, with 14 studies subjected to quality assessment. Following further evaluation, six studies were included for the final review. All six of these studies were heterogeneous in regard to CVD/risk factor as outcome, gene mapping approach, and in different targeted genes. The associated genes were RGS2, LPA, and AQP3, alongside microRNAs miR-122-5p, miR-126-3p, miR-146a-5p, and miR-206. Additionally, 12 differentially methylated regions potentially linked to later-life CVD following PE were identified. The only common variable across all six studies was the use of a case-control study design. Our results provide critical insight into the heterogeneous nature of genomic studies investigating CVD following PE and highlight the urgent need for longitudinal studies to further investigate the genetic variation underlying the progression to CVD following PE.

Long-Term Impacts of Preeclampsia on the Cardiovascular System of Mother and Offspring.

Preeclampsia is a pregnancy-specific complication that is associated with an increased postpartum risk of cardiovascular disease (CVD) in both women and their offspring, although the underlying mechanisms have yet to be fully elucidated. Nevertheless, differential methylation of cytosine-phosphate-guanosine islands and alterations in the expression of microRNA, associated with an elevated risk of CVD, have been observed in women and their children following preeclampsia. Among this specific population, genetic and epigenetic factors play crucial roles in the development of CVD in later life. A series of biomolecules involved in inflammation, oxidative stress, and angiogenesis may link pregnancy vascular bed disorders in preeclampsia to the pathogenesis of future CVD and thus could be valuable for the prediction and intervention of long-term CVD in women with a history of preeclampsia and their offspring. Here, we present insights into the cardiovascular structure and functional changes of women with a history of preeclampsia and their offspring. With a focus on various underlying mechanisms, the conclusions from this review are expected to provide more potential diagnostics and treatment strategies for clinical practice.

ASSOCIATIONS OF LONG-TERM VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY WITH SUBCLINICAL KIDNEY DAMAGE AND ALBUMINURIA IN ADULTHOOD: A 30-YEAR PROSPECTIVE COHORT STUDY

Objective: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with the risk of cardiovascular disease. We therefore aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood. Design and method: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BP variability by standard deviation (SD) and average real variability (ARV) for 30 years (6 visits). Presence of SKD was defined as estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/ 1.73 m2 or elevated urinary albumin-to creatinine ratio (uACR) at least 30 mg/g. Albuminuria was defined as uACR greater than 30 mg/g. Results: During a follow-up of 30 years, of the 1771 participants, 204 SKD events occurred. After adjustment for demographic, clinical characteristics and mean BP during 30 years, higher SDSBP, ARVSBP, SDDBP, ARVDBP, SDMAP, ARVMAP and ARVPP were significantly associated with higher risk of SKD [ORs (95% CIs) were 1.14(1.06 - 1.23), 1.15(1.08 - 1.21), 1.12(1.06 - 1.17), 1.16(1.08 - 1.25), 1.12(1.07 - 1.17), 1.18(1.10 - 1.27) and 1.11(1.03 - 1.21), respectively]. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria [ORs (95% CIs) were 1.07(1.03 - 1.10) for SDSBP, 1.13(1.06 - 1.20) for ARVSBP, 1.11(1.06 - 1.17) for SDDBP, 1.14(1.06 - 1.23) for ARVDBP, 1.18(1.09 - 1.27) for ARVMAP and 1.08(1.01 - 1.17) for ARVPP]. Long-term BP variability for 30 years from childhood to middle age was associated with higher risk of SKD and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up. Conclusions: Identifying long-term BP variability from early age may assist in predicting kidney disease and cardiovascular disease in later life.

The Impact of Bisphenol A Exposure during Pregnancy on the Heart of Mother and Fetal Rats

In utero bisphenol A (BPA) exposure has been reported to increase the risk of cardiovascular disease (CVD) in adult life. Thus, this study aimed to investigate the impact of in utero BPA exposure on proteins expression related to cardiac function in heart of rat foetuses (Rattus norvegicus). In here, pregnant rats were divided into tween-80 (vehicle control), 0.05 mg/mL and 0.2 mg/mL BPA via drinking water for 19 days: from pregnancy day 2 till 21. Caesarean section was conducted on pregnancy day 21 to collect plasma and heart of both mother and foetuses. BPA-exposed pregnant rats showed significant increase in blood pressure (BP) and reduction in glycogen content (p<0.05) in comparison to control pregnant rats. Remarkably, reduced expression of cardiac troponin I (cTnI) and redistribution of alpha fetoprotein (AFP) expression were in foetus of BPA-exposed mother in comparison with foetus of control mother. Hypoxia induced factor-1 alpha (HIF-1α) expression was elevated in BPA-exposed foetal heart compared to the control. The findings in here suggest the risk of in utero BPA exposure on both foetus and mother, which may increase the risk of CVD in later life by altering the expression of protein crucial for heart development and function.

Risk factors for arterial hypertension in women with abdominal obesity and hypertensive disorders of pregnancy in the history

The article provides data from epidemiological studies on the correlation between hypertensive disorders in pregnant women and the risk of cardiovascular diseases in later life, describes possible pathophysiological determinants for the occurrence of arterial hypertension after complicated pregnancy. The most informative predictors of the development of arterial hypertension in women with abdominal obesity are described, which were indicators of waist circumference, uterine artery resistance index, N-terminal fragment of the brain natriuretic peptide and highly sensitive C-reactive protein; a mathematical model was calculated to predict the probability of developing arterial hypertension in women with abdominal obesity and hypertensive disorders of pregnancy one year after delivery.

Abstract 18: Impact of Preeclampsia on Cardiovascular Risk Factors in Mothers and Newborns

Introduction: Preeclampsia is a multifactorial disease and a cause of maternal and neonatal morbidity and mortality. Women with preeclampsia have increased risk of cardiovascular diseases in later life. The impact on the offspring is, however, still uncertain. Lipid traits in newborns are considered to reflect the child’s own production. Hypothesis: We assessed the hypothesis that preeclampsia increases risk of future cardiovascular disease in both mother and offspring. Methods: For this purpose, we used the Copenhagen General Population Study comprising 59,571 women of which 1,365 had a diagnosis of preeclampsia to investigate the association between preeclampsia and risk of cardiovascular diseases. Further, we used the Copenhagen Baby Heart Study comprising more than 13,000 umbilical cord blood samples and assessed the impact of preeclampsia on atherogenic lipid traits in cord blood. Results: Age adjusted hazard ratios for preeclampsia versus no preeclampsia (95% CI) were 1.48 (1.13-1.94) for ischemic heart disease, 1.50 (1.07-2.12) for ischemic cerebrovascular disease, and 1.53 (1.22-1.91) for composite vascular disease. Corresponding multivariable adjusted hazard ratios (95% CI) were 1.31 (1.00-1.72), 1.44 (1.02-2.02), and 1.39 (1.11-1.74). Concentrations of non-HDL cholesterol, total cholesterol, LDL cholesterol, apolipoprotein B, and triglycerides in cord blood increased stepwise from no preeclampsia (n=11,221) to mild/moderate preeclampsia (n=253) to severe preeclampsia (n=104) (p for trends <0.0001 for non-HDL cholesterol, total cholesterol and LDL cholesterol; p for trend=0.0002 for apolipoprotein B; p for trend=0.003 for triglycerides). Multivariable adjusted odds ratios (95% CI) for preeclampsia versus no preeclampsia (reference) for cord blood concentrations above the 80 th percentile were 2.09 (1.67-2.61) for non-HDL cholesterol, 1.58 (1.25-2.01) for total cholesterol, 1.72 (1.37-2.16) for LDL cholesterol, 1.38 (1.07-1.78) for apolipoprotein B, and 2.64 (2.07-3.35) for triglycerides. Conclusion: Women with preeclampsia had increased risk of future cardiovascular disease and lipid traits in umbilical cord blood of their offspring were elevated. This indicates that preeclampsia affects lipid metabolism during fetal life and potentially contributes to an increased risk of future cardiovascular disease in offspring of mothers with preeclampsia.

Preeclampsia and Obesity-The Preventive Role of Exercise.

Obesity is now recognized as a worldwide epidemic. An inadequate diet and reduced physical activity are acknowledged as the leading causes of excess body weight. Despite growing evidence that obesity is a risk factor for unsuccessful pregnancies, almost half of all women who become pregnant today are overweight or obese. Common complications of pregnancy in this group of women are preeclampsia and gestational hypertension. These conditions are also observed more frequently in women with excessive weight gain during pregnancy. Preeclampsia is one of the most serious pregnancy complications with an unpredictable course, which in its most severe forms, threatens the life and health of the mother and her baby. The early identification of the risk factors for preeclampsia development, including obesity, allows for the implementation of prophylaxis and a reduction in maternal and fetal complications risk. Additionally, preeclampsia and obesity are the recognized risk factors for developing cardiovascular disease in later life, so prophylaxis and treating obesity are paramount for their prevention. Thus, a proper diet and physical activity might play an essential role in the prophylaxis of preeclampsia in this group of women. Limiting weight gain during pregnancy and modifying the metabolic risk factors with regular physical exercise creates favorable metabolic conditions for pregnancy development and benefits the elements of the pathogenetic sequence for preeclampsia development. In addition, it is inexpensive, readily available and, in the absence of contraindications to its performance, safe for the mother and fetus. However, for this form of prevention to be effective, it should be applied early in pregnancy and, for overweight and obese women, proposed as an essential part of planning pregnancy. This paper aims to present the mechanisms of the development of hypertension in pregnancy in obese women and the importance of exercise in its prevention.

JS-HR-4: PREECLAMPSIA UP TO DATE; WHAT WE SHOULD KNOW FOR MOTHER AND CHILD.

Preeclampsia (PE) is a systemic hypertensive disorder of pregnancy thought to arise from placental maladaptation and subsequent systemic inflammatory processes. PE is associated with significant maternal and fetal mortality with hypertensive disorder of pregnancy accounting for -14% of maternal deaths globally and also with increased maternal risks for chronic diseases in later life. In 2017, the American College of Cardiology/American Heart Association hypertension treatment guidelines identified hypertension as blood pressure (BP) 130/80 mmHg. The reference BP for hypertension during pregnancy as specified in international guidelines is still > 140/90 mmHg. Also, recommended target BP level differs between these guidelines. A large number of studies have been examining the incidence of PE and fetal outcomes according to BP levels to figure out the optimal level for pregnant women. Given only termination of pregnancy has been proved to initiate the resolution of PE once it has developed, prevention of PE is a health care priority. However, the predictive value of BP and other clinical characteristics for PE is relatively low, and therefore, improved method for the prediction of PE and associated adverse outcomes is required. Past history of PE is now widely known to link with major chronic diseases such as hypertension, type 2 diabetes mellitus, dyslipidemia, cardiovascular disease in later life. Since many cardiovascular risk factors are modifiable and related to lifestyle, all women with prior PE should be followed-up by physician even after resolution of PE (eg. hypertension, proteinuria). However, no long-term follow-up strategy for former-PE patient has yet been established. The 2019 Maternal Mortality update from the WHO report indicated the major contribution of PE and eclampsia to worldwide maternal deaths. Further investigation is needed to decrease PE related maternal and fetal deaths and also to reduce maternal risks for chronic diseases in later life. Participation of physicians is necessary to offer appropriate medical care to women with prior PE.

Clusters of lifestyle behaviors associated with atherosclerosis risk factors in children and adolescents with congenital heart disease: Floripa CHild Study.

Secondary cardiovascular disease is the main cause of mortality in congenital heart disease (CHD) patients. The cardiovascular risk could be widely prevented with adherence to a healthy lifestyle, however, clusters of lifestyle behaviors related to atherosclerosis risk factors in children and adolescents with CHD remain unclear. We aimed to describe the clusters of lifestyle behaviors of children and adolescents with CHD and to evaluate their association with atherosclerosis risk factors. Cross-sectional study on 227 children and adolescents with CHD (median age: 10.02 [IQR:7.08-13.02] years). Dietary intake, physical activity (PA), and sedentary behavior (SB) were evaluated. Clusters of lifestyle behaviors were determined using two-step cluster analysis. Atherosclerosis risk factors evaluated include body fat mass, central obesity, blood pressure, lipid parameters, glucose, C-reactive protein, and carotid intima-media thickness (cIMT). Multiple logistic regressions were used. The "unhealthy:high SB+low PA" cluster was associated with elevated body fat mass, central obesity, and elevated cIMT. Furthermore, the "unhealthy:low PA+unhealthy eating habits" cluster was associated with elevated body fat mass, central obesity, and elevated glucose. The unhealthier lifestyle behavior clusters were associated with atherosclerosis risk factors in children and adolescents with CHD. Multidisciplinary strategies to promote healthy behaviors are needed to prevent cardiovascular disease in later life.

Differential affinity chromatography reveals a link between Porphyromonas gingivalis-induced changes in vascular smooth muscle cell differentiation and the type 9 secretion system.

Porphyromonas gingivalis is implicated in adverse pregnancy outcome. We previously demonstrated that intrauterine infection with various strains of P. gingivalis impairs the physiologic remodeling of the uterine spiral arteries (IRSA) during pregnancy, which underlies the major obstetrical syndromes. Women diagnosed with IRSA also have a greater risk for premature cardiovascular disease in later life. The dysregulated plasticity of vascular smooth muscle cells (VSMCs) is present in both IRSA and premature cardiovascular events. We hypothesized that VSMCs could serve as a bait to identify P. gingivalis proteins associated with dysregulated VSMC plasticity as seen in IRSA. We first confirmed that dams with P. gingivalis A7UF-induced IRSA also show perturbed aortic smooth muscle cell (AoSMC) plasticity along with the P. gingivalis colonization of the tissue. The in vitro infection of AoSMCs with IRSA-inducing strain A7UF also perturbed AoSMC plasticity that did not occur with infection by non-IRSA-inducing strain W83. Far-Western blotting with strain W83 and strain A7UF showed a differential binding pattern to the rat aorta and primary rat AoSMCs. The affinity chromatography/pull-down assay combined with mass spectrometry was used to identify P. gingivalis/AoSMC protein interactions specific to IRSA. Membrane proteins with a high binding affinity to AoSMCs were identified in the A7UF pull-down but not in the W83 pull-down, most of which were the outer membrane components of the Type 9 secretion system (T9SS) and T9SS cargo proteins. Additional T9SS cargo proteins were detected in greater abundance in the A7UF pull-down eluate compared to W83. None of the proteins enriched in the W83 eluate were T9SS components nor T9SS cargo proteins despite their presence in the prey preparations used in the pull-down assay. In summary, differential affinity chromatography established that the components of IRSA-inducing P. gingivalis T9SS as well as its cargo directly interact with AoSMCs, which may play a role in the infection-induced dysregulation of VSMC plasticity. The possibility that the T9SS is involved in the microbial manipulation of host cell events important for cell differentiation and tissue remodeling would constitute a new virulence function for this system.

Preterm birth and metabolic implications on later life: A narrative review focused on body composition.

Preterm newborn infants are characterized by low body weight and lower fat mass at birth compared with full-term newborn neonates. Conversely, at term corrected age, body fat mass is more represented in preterm newborn infants, causing a predisposition to developing metabolic syndrome and cardiovascular diseases in later life with a different risk profile in men as compared with women. Postnatal growth is a complex change in anthropometric parameters and body composition. Both quantity and quality of growth are regulated by several factors such as fetal programming, early nutrition, and gut microbiota. Weight gain alone is not an optimal indicator of nutritional status as it does not accurately describe weight quality. The analysis of body composition represents a potentially useful tool to predict later metabolic and cardiovascular risk as it detects the quality of growth by differentiating between fat and lean mass. Longitudinal follow-up of preterm newborn infants could take advantage of body composition analysis in order to identify high-risk patients who apply early preventive strategies. This narrative review aimed to examine the state-of-the-art body composition among born preterm children, with a focus on those in the pre-school age group.

Cardiometabolic Risks in Gestational Diabetes Mellitus: A Mini-Review

Diabetes is one of the most common medical problems encountered in about 3.8% - 41% of pregnancies across the various parts of India. It contributes to maternal morbidity and mortality, especially in developing countries. Insulin resistance and β – cell dysfunction are the characteristics of GDM. Women with GDM had many immediate adverse fetomaternal and neonatal outcomes. In addition to the immediate adverse outcomes, women with GDM also had long-term complications such as dyslipidemia, metabolic syndrome, hypertension, type 2 diabetes, cardiovascular disease in later life. Current evidence suggests that GDM is highly associated with cardiometabolic risks (CMR) during gestation and in post-gestational period. Though the mechanism behind the pathogenesis of CMR in GDM is multifactorial, placental hormones, inflammation, endothelial dysfunction and oxidative stress play a significant role in the pathophysiology of cardiovascular risks in pregnant women with GDM.

Chronic developmental hypoxia alters mitochondrial oxidative capacity and reactive oxygen species production in the fetal rat heart in a sex-dependent manner.

Insufficient oxygen supply (hypoxia) during fetal development leads to cardiac remodeling and a predisposition to cardiovascular disease in later life. Previous work has shown hypoxia causes oxidative stress in the fetal heart and alters the activity and expression of mitochondrial proteins in a sex‐dependent manner. However, the functional effects of these modifications on mitochondrial respiration remain unknown. Furthermore, while maternal antioxidant treatments are emerging as a promising new strategy to protect the hypoxic fetus, whether these treatments convey similar protection to cardiac mitochondria in the male or female fetus has not been investigated. Therefore, using an established rat model, we measured the sex‐dependent effects of gestational hypoxia and maternal melatonin treatment on fetal cardiac mitochondrial respiration, reactive oxygen species (ROS) production, and lipid peroxidation. Pregnant Wistar rats were subjected to normoxia or hypoxia (13% oxygen) during gestational days (GDs) 6–20 (term ~22 days) with or without melatonin treatment (5 µg/ml in maternal drinking water). On GD 20, mitochondrial aerobic respiration and H2O2 production were measured in fetal heart tissue, together with lipid peroxidation and citrate synthase (CS) activity. Gestational hypoxia reduced maternal body weight gain (p < .01) and increased placental weight (p < .05) but had no effect on fetal weight or litter size. Cardiac mitochondria from male but not female fetuses of hypoxic pregnancy had reduced respiratory capacity at Complex II (CII) (p < .05), and an increase in H2O2 production/O2 consumption (p < .05) without any changes in lipid peroxidation. CS activity was also unchanged in both sexes. Despite maternal melatonin treatment increasing maternal and fetal plasma melatonin concentration (p < .001), melatonin treatment had no effect on any of the mitochondrial parameters investigated. To conclude, we show that gestational hypoxia leads to ROS generation from the mitochondrial electron transport chain and affects fetal cardiac mitochondrial respiration in a sex‐dependent manner. We also show that maternal melatonin treatment had no effect on these relationships, which has implications for the development of future therapies for hypoxic pregnancies.

Early life exposure to the Chinese Famine of 1959-1961 is an independent risk factor of adulthood elevated homocysteine, hyperuricemia, high LDL, and hypertension.

Famine exposure in early life was associated with cardiovascular diseases in later life. Whether biochemical surrogates of cardiovascular diseases, such as homocysteine and uric acid, are also associated with famine exposure is unknown so far. Data were derived from a population-based cross-sectional study in the Hunan Province of China, which was heavily affected by the Famine in 1959-1961. A total of 1,150 adults born between 1952and1964 were selected, and 5 cohorts were defined: no exposure, fetal, early childhood, mid-childhood, and late childhood exposure. Compared with the no-famine exposure group, participants exposed to famine in their fetal period had a higher risk of high homocysteine in adulthood with OR of 2.21 (95% CI: 1.01-4.83), whereas famine exposures in early, mid, or late childhood were not significantly associated with high homocysteine in adulthood. Similarly, participants in the fetal famine exposure group had a 1.59-fold higher risk of hyperuricemia (OR = 2.59, 95% CI: 1.07-5.30) and a 2.03-fold higher risk of high low-density lipoprotein cholesterol (LDL) (OR = 0.03, 95% CI: 1.35-6.78) in adulthood compared to those without famine exposure, respectively. We furthermore conducted a meta-analysis including 16 studies regarding the association between fetal famine exposure and adulthood hypertension, including our study. The meta-analysis, including 34,804, subjects showed that fetal famine exposure is associated with a higher risk of adulthood hypertension (OR=1.22, 95% CI: 1.07-1.40). Taken together, fetal famine exposure is related to higher odds of cardio-metabolic risk factors, such as high homocysteine, hyperuricemia, and LDL as well as hypertension, suggesting that undernutrition during fetal life may affect metabolism of homocysteine, uric acid, and LDL in adulthood.

FAMINE EXPOSURE IN EARLY-LIFE AND HIGH CARDIOVASCULAR RISK IN ADULTHOOD: FINDINGS FROM THE CHINA PATIENT-CENTERED EVALUATIVE ASSESSMENT OF CARDIAC EVENTS MILLION PERSONS PROJECT

Objective: Previous studies reported that early-life exposure to undernutrition play key roles in the development of metabolic diseases, but the association with high cardiovascular disease (CVD) risk in later life remains unclear. We aimed to investigate whether exposure to famine in early life is associated with high cardiovascular disease (CVD) risk in adulthood. Design and method: This study included 85,473 participants from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project in southern China who were born around the time of the Chinese Great Famine. They were divided into four famine exposure groups according to the birth year, including nonexposed (1963–1974), fetal exposed (1959–1962), childhood exposed (1949–1958), and adolescent exposed (1941–1948). High CVD risk was defined as having previous heart disease or a predicted 10-year risk of CVD greater than 20% based on the WHO/ISH criteria. Logistic regression models were used to examine the association between famine exposure and high CVD risk. Results: Among the participants included, 4.6% (3893) participants had high risk for CVD, including 2543 (3.0%) participants had a predicted 10-year risk of CVD greater than 20%. Compared with the nonexposed group, childhood-exposed and adolescent exposed but not fetal-exposed participants had increased risk of having high CVD risk in adulthood, with odd ratios (ORs) (95% CIs) of 1.40 (1.15–1.70), 1.43 (1.07–1.90) and 1.14 (0.97–1.33), respectively, after adjusting for age and other covariates. For individuals without previous heart disease, fetal, childhood, and adolescent famine exposure were associated with higher likelihood of predicted 10-year risk of CVD greater than 20%, with multivariable-adjusted ORs (95%CI) of 1.34 (1.08–1.66), 2.17 (1.69–2.78), and 2.84 (1.98–4.07). Sensitivity analysis showed similar results by combining the relatively older and younger age group as the reference, which neutralized the age gap between the nonexposed group and the exposed groups in the main analysis. Conclusions: Early-life exposure to famine is significantly associated with higher risk of developing CVD in later life. These findings have important epidemiological and clinical implications on the understanding and prevention of CVD.

ASSOCIATIONS OF LONG-TERM VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY WITH SUBCLINICAL RENAL DAMAGE AND ALBUMINURIA IN ADULTHOOD: A 30-YEAR PROSPECTIVE COHORT STUDY

Objective: To determine the potential associations of long-term BPV from childhood to middle age with subclinical renal damage (SRD) and albuminuria in adulthood, independently of mean BP and cumulative exposure to BP. Design and method: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and young adults aged 6 to 18 years at baseline, we assessed BP variability by standard deviation (SD) and average real variability (ARV) for 30 years (6 visits). Results: During a follow-up of 30 years, of the 1115 participants, 146 SRD events occurred. After adjustment for demographic, clinical characteristics and mean BP during 30 years, higher SDSBP, ARVSBP, SDDBP, ARVDBP, SDMAP and ARVMAP were significantly associated with higher risk of SRD [ORs (95% CIs) were 1.06(1.03–1.10), 1.12(1.06–1.19), 1.17(1.11–1.23), 1.22(1.13–1.32), 1.13(1.08,1.19) and 1.21(1.12–1.31), respectively]. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria [ORs (95% CIs) were 1.06(1.12–1.10) for SDSBP, 1.12(1.06–1.19) for ARVSBP, 1.14(1.08–1.21) for SDDBP, 1.19(1.10–1.30) for ARVDBP, 1.13(1.07–1.19) for SDMAP, and 1.20(1.11–1.32) for ARVMAP] adjusting for demographic, clinical characteristics, mean BP or cumulative exposure to BP during 30 years. Conclusions: Long-term BP variability for 30 years from childhood to middle age was associated with higher risk of subclinical renal damage and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up. Identifying long-term BP variability from early age may assist in predicting renal disease and cardiovascular disease in later life.

Advanced Maternal Age and Its Association With Cardiovascular Disease in Later Life.

Fertility among women at advanced maternal age (AMA) is increasing at a rapid rate in the United States. Although much is known about the impact of older maternal age on the risk for proximate adverse pregnancy outcomes, it is unclear whether older maternal age affects subsequent health. The objective of this study was to evaluate whether AMA is associated with cardiovascular disease (CVD) later in life, adjusting for important social and health factors related to maternal age. Data were obtained from the Nurses' Health Study II, a longitudinal prospective cohort study. We investigated whether women with an AMA first or subsequent birth were at higher risk for developing CVD (myocardial infarction or stroke) after age 42 than women without births at AMA. Cox proportional hazard models were estimated to evaluate this association, adjusting for demographic, fertility, and health characteristics. A total of 5,471 women (7.7%) in the sample had a first birth at an AMA and 1,282 (1.8%) developed CVD at age 42 or older. Women with first births at AMA had a 26% lower unadjusted hazard of CVD than women not at an AMA during their first birth (hazard ratio, 0.74; 95% confidence interval, 0.57-0.95). This association was attenuated (hazard ratio, 0.80; 95% confidence interval, 0.62-1.05) and no longer significant after adjustment for covariates; the modest association remained significant for women with any AMA birth. We found no evidence that AMA births were associated with increased risk for developing CVD later in life in this sample.

Protein Restriction in the Peri-Pubertal Period Induces Autonomic Dysfunction and Cardiac and Vascular Structural Changes in Adult Rats.

Perturbations to nutrition during critical periods are associated with changes in embryonic, fetal or postnatal developmental patterns that may render the offspring more likely to develop cardiovascular disease in later life. The aim of this study was to evaluate whether autonomic nervous system imbalance underpins in the long-term hypertension induced by dietary protein restriction during peri-pubertal period. Male Wistar rats were assigned to groups fed with a low protein (4% protein, LP) or control diet (20.5% protein; NP) during peri-puberty, from post-natal day (PN) 30 until PN60, and then all were returned to a normal protein diet until evaluation of cardiovascular and autonomic function at PN120. LP rats showed long-term increased mean arterial pressure (p = 0.002) and sympathetic arousal; increased power of the low frequency (LF) band of the arterial pressure spectral (p = 0.080) compared with NP animals. The depressor response to the ganglion blocker hexamethonium was increased in LP compared with control animals (p = 0.006). Pulse interval variability showed an increase in the LF band and LF/HF ratio (p = 0.062 and p = 0.048) in LP animals. The cardiac response to atenolol and/or methylatropine and the baroreflex sensitivity were similar between groups. LP animals showed ventricular hypertrophy (p = 0.044) and increased interstitial fibrosis (p = 0.028) compared with controls. Reduced protein carbonyls (PC) (p = 0.030) and catalase activity (p = 0.001) were observed in hearts from LP animals compared with control. In the brainstem, the levels of PC (p = 0.002) and the activity of superoxide dismutase and catalase (p = 0.044 and p = 0.012) were reduced in LP animals, while the levels of GSH and total glutathione were higher (p = 0.039 and p = 0.038) compared with NP animals. Protein restriction during peri-pubertal period leads to hypertension later in life accompanied by sustained sympathetic arousal, which may be associated with a disorganization of brain and cardiac redox state and structural cardiac alteration.