Risk Of Future Cardiovascular Disease Research Articles

Preventing Adverse Cardiovascular Outcomes in Pregnancy Complicated by Obesity.

Obesity is a chronic disease that is becoming increasingly prevalent, and more individuals of reproductive age have obesity prior to becoming pregnant. Obesity in pregnancy is associated with short- and long-term adverse consequences for both the birthing person and their offspring which have been associated with increased long-term cardiovascular morbidity and mortality. The goal of this review is to discuss what is currently understood about the relationship between maternal obesity and adverse pregnancy outcomes (APOs), the association between APOs and future cardiovascular disease (CVD) risk, and what evidence-based interventions can be implemented to prevent adverse outcomes in this population. Maternal obesity has been associated with an increased risk of APOs such as gestational diabetes, hypertensive disorders of pregnancy, and preterm birth as well as an increased risk of future CVD, such as metabolic syndrome, chronic hypertension, coronary heart disease, and stroke. The impact of maternal obesity also extends beyond the pregnant individual to the offspring, increasing the risk of fetal, neonatal, and infant mortality, as well as of congenital malformations, prematurity, and long-term health problems such as insulin resistance and childhood obesity. Prevention guidelines are incorporating the increased risk of adverse outcomes from maternal obesity into formalized risk assessments to guide both prenatal and postpartum care. It is becoming evident that a multidisciplinary cardio-obstetrics team is an important part of providing comprehensive care for pregnant individuals with obesity and other cardiovascular risk factors, including preexisting CVD and a history of prior APOs. There remains a need for further studies to better understand the mechanisms underlying the relationship between maternal obesity and APOs, as well as the racial and ethnic disparities that have been noted in the prevalence of APOs and associated CVD risk and mortality. There is increasing awareness that obesity in pregnancy is associated with various short- and long-term adverse maternal and offspring outcomes. There are multiple screening and prevention strategies that may be implemented before, during, and after pregnancy to prevent these adverse outcomes.

Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events

The prevalence of antiphospholipid antibodies (aPL) and their association with future atherosclerotic cardiovascular disease (ASCVD) risk has yet to be thoroughly investigated. To determine the association between measurements of aPL at a single time point and ASCVD risk in a diverse population. This cohort study measured 8 aPL (anticardiolipin [aCL] IgG/IgM/IgA, anti-beta-2 glycoprotein I [aβ2GPI] IgG/IgM/IgA, and antiphosphatidylserine/prothrombin [aPS/PT] IgG/IgM) by solid-phase assays in plasma from participants of the Dallas Heart Study (DHS) phase 2, a multiethnic, population-based cohort study. Blood samples were collected between 2007 and 2009. The median follow-up was 8 years. Statistical analysis was performed from April 2022 to January 2023. Associations of aPL with future ASCVD events (defined as first nonfatal myocardial infarction, first nonfatal stroke, coronary revascularization, or death from cardiovascular cause) were assessed by Cox proportional hazards models, adjusting for known risk factors, medications, and multiple comparisons. Among the 2427 participants (mean [SD] age, 50.6 [10.3] years; 1399 [57.6%] female; 1244 [51.3%] Black, 339 [14.0%] Hispanic, and 796 [32.8%] White), the prevalence of any positive aPL tested at a single time point was 14.5% (353 of 2427), with approximately one-third of those detected at a moderate or high titer; aCL IgM had the highest prevalence (156 individuals [6.4%]), followed by aPS/PT IgM (88 [3.4%]), aβ2GPI IgM (63 [2.6%]), and aβ2GPI IgA (62 [2.5%]). The IgA of aCL (adjusted hazard ratio [HR], 4.92; 95% CI, 1.52-15.98) and aβ2GPI (HR, 2.91; 95% CI, 1.32-6.41) were independently associated with future ASCVD events. The risk further increased when applying a positivity threshold of at least 40 units (aCL IgA: HR, 9.01 [95% CI, 2.73-29.72]; aβ2GPI IgA: HR, 4.09 [95% CI, 1.45-11.54]). Levels of aβ2GPI IgA negatively correlated with cholesterol efflux capacity (r = -0.055; P = .009) and positively correlated with circulating oxidized LDL (r = 0.055; P = .007). aβ2GPI IgA-positive plasma was associated with an activated endothelial cell phenotype as evidenced by increased surface expression of surface E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. In this population-based cohort study, aPL detectable by solid-phase assays were present in a substantial proportion of adults; positive aCL IgA and aβ2GPI IgA at a single time point were independently associated with future ASCVD events. Longitudinal studies with serial aPL measurements are needed to further explore these findings.

Effects of a school-based physical activity intervention on cardiometabolic health five years after cessation.

While there have been several school-based physical activity (PA) interventions targeting improvement in cardiovascular disease (CVD) risk factors, few have assessed long-term effects. The aim of this paper was therefore to determine intervention effects on CVD risk factors five years after cessation. Two schools were assigned to intervention (n=125) or control (n=134). The intervention school offered 210 min/week more PA than the control school over two consecutive years (4th and 5th grades). Follow-up assessment was conducted five-year post intervention (10th grade) where 180-210 (73-85%) children provided valid data. Outcomes were CVD risk factors: triglyceride (TG), total-to-high-density-lipoprotein-cholesterol ratio (TC:HDL ratio), insulin resistance (HOMA), blood pressure (BP), waist circumference (WC), and cardiorespiratory fitness (VO2peak ). Variables were analyzed individually and as a composite score through linear mixed models, including random intercepts for children. Analyses revealed significant sustained five-year intervention effects for HDL (ES=.22), diastolic BP (ES=.48), VO2peak (ES=.29), and composite risk score (ES=.38). These effects were similar to the immediate results following the intervention. In contrast, while TC:HDL ratio initially decreased post intervention (ES=.27), this decrease was not maintained at five-year follow-up (ES=.09), whereas WC was initially unchanged post intervention (ES=.02), but decreased at five-year follow-up (ES=.44). The significant effects of a two-year school-based PA intervention remained for CVD risk factors five years after cessation of the intervention. As cardiometabolic health can be maintained long-term after school-based PA, this paper demonstrates the sustainability and potential of schools in the primary prevention of future CVD risk in children.

Proteomics and lipidomics in atherosclerotic cardiovascular disease risk prediction.

Given the limited accuracy of clinically used risk scores such as the Systematic COronary Risk Evaluation 2 system and the Second Manifestations of ARTerial disease 2 risk scores, novel risk algorithms determining an individual's susceptibility of future incident or recurrent atherosclerotic cardiovascular disease (ASCVD) risk are urgently needed. Due to major improvements in assay techniques, multimarker proteomic and lipidomic panels hold the promise to be reliably assessed in a high-throughput routine. Novel machine learning-based approaches have facilitated the use of this high-dimensional data resulting from these analyses for ASCVD risk prediction. More than a dozen of large-scale retrospective studies using different sets of biomarkers and different statistical methods have consistently demonstrated the additive prognostic value of these panels over traditionally used clinical risk scores. Prospective studies are needed to determine the clinical utility of a biomarker panel in clinical ASCVD risk stratification. When combined with the genetic predisposition captured with polygenic risk scores and the actual ASCVD phenotype observed with coronary artery imaging, proteomics and lipidomics can advance understanding of the complex multifactorial causes underlying an individual's ASCVD risk.

Comparison of anthropometric parameters and laboratory test results before and after the COVID-19 outbreak among Chinese children aged 3-18 years.

To compare the physiological health of Chinese children around the COVID-19 lockdown. We extracted data on children's anthropometric and laboratory parameters from May to November in both 2019 and 2020 from the Health Checkup Center, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China. Overall, 2162 children aged 3~18 years without comorbidities in 2019 and 2646 in 2020 were assessed. Mann Whitney U tests were used to compare differences between the above health indicators before and after COVID-19 outbreak. Quantile regression analyses adjusted for age, sex and body mass index (BMI) were also used in analysis. Chi-square tests and Fisher's exact tests were used for comparing differences of categorical variables. Compared with children examined in 2019 before the outbreak, children in 2020 had a higher median z score of BMI for age (-0.16 vs. -0.31), total cholesterol (TC, 4.34 vs. 4.16 mmol/L), low density lipoprotein cholesterol (LDL-C, 2.48 vs. 2.15 mmol/L), high density lipoprotein cholesterol (HDL-C, 1.45 vs. 1.43 mmol/L) and serum uric acid (290 vs. 282 μmol/L), and a lower hemoglobin (Hb, 134 vs. 133 g/L), triglycerides (TG, 0.70 vs. 0.78 mmol/L) and 25(OH)D (45.8 vs. 52.2 nmol/L), all P < 0.05. No differences were identified for waist height ratio, blood pressure and fasting glucose (both P > 0.05). However, in regression models after adjusting, BMI, TC, LDL-C, blood glucose and sUA were positively correlated with year; while Hb, TG and 25(OH)D were negatively correlated with year (all P < 0.05). Accordingly, children in 2020 had a higher prevalence of overweight/obesity (20.6 vs. 16.7%, P < 0.001), hypercholesterol (16.2%vs. 10.2%, P < 0.001), high LDL-C (10 vs. 2.9%, P < 0.001), hyperuricemia (18.9 vs.15.1%, P = 0.002), vitamin D deficiency (22.6 vs. 8.1%, P < 0.001) and a lower prevalence of high TG (4.3 vs. 2.8%, P = 0.018) compared with children in 2019. In this real-world study, we found that long-term lockdown due to COVID-19 outbreak might cause adverse impact on children's metabolic health, which might increase their future risk of cardiovascular diseases. Thus, parents, health professionals, educationists, and caregivers should pay more attention to children's dietary pattern and lifestyle, especially in this new normal against COVID-19.

Family History of Modifiable Risk Factors and Association With Future Cardiovascular Disease.

Background A parental history of cardiovascular disease (CVD) confers greater risk of future CVD among offspring. Whether the presence of parental modifiable risk factors contribute to or modify CVD risk in offspring is unclear. Methods and Results We studied 6278 parent-child trios in the multigenerational longitudinal Framingham Heart Study. We assessed parental history of CVD and modifiable risk factors (smoking, hypertension, diabetes, obesity, and hyperlipidemia). Multivariable Cox models were used to evaluate the association of parental history and future CVD among offspring. Among 6278 individuals (mean age 45±11 years), 44% had at least 1 parent with history of CVD. Over a median follow-up of 15 years, 353 major CVD events occurred among offspring. Parental history of CVD conferred 1.7-fold increased hazard of future CVD (hazard ratio[HR], 1.71 [95% CI, 1.33-2.21]). Parental obesity and smoking status were associated with higher hazard of future CVD (obesity: HR, 1.32 [95% CI, 1.06-1.64]; smoking: HR, 1.34 [95% CI, 1.07-1.68], attenuated after adjusting for offspring smoking status). By contrast, parental history of hypertension, diabetes, and hypercholesterolemia were not associated with future CVD in offspring (P>0.05 for all). Furthermore, parental risk factors did not modify the association of parental CVD history on future offspring CVD risk. Conclusions Parental history of obesity and smoking were associated with a higher hazard of future CVD in offspring. By contrast, other parental modifiable risk factors did not alter offspring CVD risk. In addition to parental CVD, the presence of parental obesity should prompt a focus on disease prevention.

Vasomotor symptoms and risk of cardiovascular disease in peri- and postmenopausal women: A systematic review and meta-analysis

IntroductionVasomotor symptoms (VMS) are the symptoms most frequently experienced by women transitioning to menopause and are a primary indication for menopausal hormone therapy. A growing body of evidence has associated the presence of VMS with future risk for cardiovascular disease (CVD) events. This study aimed to systematically evaluate, qualitatively and quantitatively, the possible association between VMS and the risk for incident CVD. MethodsThis systematic review and meta-analysis included 11 studies evaluating peri- and postmenopausal women in a prospective design. The association between VMS (hot flashes and/or night sweats) and the incidence of major adverse cardiovascular events, including coronary heart disease (CHD) and stroke, was explored. Associations are expressed as relative risks (RR) with 95 % confidence intervals (CI). ResultsThe risk for incident CVD events in women with and without VMS differed according to the age of participants. Women with VSM younger than 60 years at baseline had a higher risk of an incident CVD event than women without VSM of the same age (RR 1.12, 95 % CI 1.05–1.19, I2 0%). Conversely, the incidence of CVD events was not different between women with and without VMS in the age group >60 years (RR 0.96, 95 % CI 0.92–1.01, I2 55%). ConclusionThe association between VMS and incident CVD events differs with age. VMS increases the incidence of CVD only in women under 60 years of age at baseline. The findings of this study are limited by the high heterogeneity among studies, pertaining mainly to different population characteristics, definitions of menopausal symptoms and recall bias.

Temporal relationship between hyperuricemia and hypertension and its impact on future risk of cardiovascular disease

BackgroundAlthough hyperuricemia and hypertension are significantly correlated, their temporal relationship and whether this relationship is associated with risk of cardiovascular disease (CVD) are largely unknown. This study aimed to examine temporal relationship between hyperuricemia and hypertension, and its association with future risk of CVD. MethodsThis study included 60,285 participants from the Kailuan study. Measurement of serum uric acid (SUA), systolic and diastolic blood pressure (SBP and DBP) were obtained twice at 2006 (baseline) and 2010. Cross-lagged and mediation analysis were used to examine the temporal relationship between hyperuricemia and hypertension, and the association of this temporal relationship with CVD events risk after 2010. ResultsAfter adjusting for covariates, the cross-lagged path coefficients (β1) from baseline SUA to follow-up SBP and DBP were significantly greatly than path coefficients (β2) from baseline SBP and DBP to follow-up SUA (β1=0.041 versus β2=0.003; Pdifference<0.0001 for SBP; β1=0.040 versus β2=0.000; Pdifference<0.0001 for DBP). The path coefficients from baseline SUA to follow-up SBP and DBP in group with incident CVD were significantly greatly than that in group without incident CVD (Pdifference of β1 in the two groups was 0.0018 for SBP and 0.0340 for DBP). Furthermore, SBP and DBP partially mediated the effect of SUA on incident CVD, the mediation effect was 57.64% for SBP and 46.27% for DBP. Similar mediated results were observed for stroke and myocardial infarction. ConclusionIncreased SUA levels probably precede elevated BP, and BP partially mediates the pathway from SUA to incident CVD.

Adverse pregnancy outcomes and future risk of heart failure.

Cardiovascular disease (CVD) is the leading cause of death in women. Women with history of adverse pregnancy outcomes (APOs) have approximately two-fold risk of future CVD, but until recently the association with future heart failure (HF) was unclear. Here, we summarize evidence for associations of APOs with HF, potential underlying mechanisms, and future directions for clinical translation. Women with history of hypertensive disorders of pregnancy (HDPs) have roughly two-fold risk of future HF compared with other parous women even after accounting for interval development of coronary artery disease. The HDPs portend heightened risk of HF with both reduced and preserved ejection fraction. Gestational diabetes mellitus (GDM) and other APOs such as preterm delivery, small-for-gestational-age delivery, and placental abruption may also confer additional risk for HF development. Possible underlying mechanisms linking APOs to HF include shared upstream risk factors and genetics, accelerated development of cardiometabolic risk factors postpartum, persistent endothelial and microvascular dysfunction, and impaired natriuretic peptide signaling. History of APOs, including HDPs and GDM, confer increased risk for development of HF years after delivery. Further research is needed to define strategies to optimize prepregnancy and postpartum cardiovascular health toward HF prevention.

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 &lt;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.

Abstract P337: Determinants and Influence of Breast Arterial Calcifications on Risk of Cardiovascular Disease

Background: Breast arterial calcifications (BAC) are incidentally observed on screening mammography. BAC has been shown to be associated with the presence of coronary artery calcification (CAC) and increased risk of coronary artery disease (CAD). Given that population-based mammography is currently recommended to women, the evaluation of BAC may be important in identifying high-risk women without additional cost or radiation exposure. Aims: We sought to identify reproductive and cardiovascular risk factors associated with the presence of detectable BAC and CAC in women participated to mammography screening. Also, we aimed to determine the association between BAC and presence of CAC. Further, we investigated presence of BAC, CAC and estimated 10-year risk of atherosclerotic cardiovascular disease (ASCVD). Methods: In this cross-sectional study, reproductive history and CVD risk factors were obtained in 215 women ≥ 18 years of age that underwent mammography and cardiac computed tomographic angiography (CCTA) within 2 years of each other between January 2007 and September 2017 at Weill Cornell Medicine/ New York Presbyterian hospital (WCM/NYP). BAC was recorded in two ways: a binary scale (presence/absence) and a semi-quantitative scale (mild, moderate, severe). CAC was calculated using the Agatston method and was recorded as a binary variable (presence/absence). Information regarding reproductive history and CVD risk factors, medical history, and relevant demographics were obtained by chart review. Odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for age at study entry as a potential confounder, were estimated. The 10-year risk of atherosclerotic cardiovascular disease (ASCVD) was calculated using the Pooled Cohort Risk Equations. Results: The odds of presence of BAC increased with increasing age . Women age ≥60 had a near 6-fold higher odds of BAC (OR = 5.77; 95% CI = 2.45 to 16.00) compared with women &lt;60 years old. Other factors associated with presence of BAC after controlling for age were diastolic blood pressure ≥80 ( P = 0.0008), systolic blood pressure ≥140 ( P = 0.0009), number of children (P = 0.01). Younger age at first birth (≤28 years) was associated with 3-fold higher odds of BAC compared with women with age at first birth &gt;28 years. Except for age at study entry, the only factor associated with presence of CAC was hyperlipidemia ( P = 0.002). We found no association between presence of BAC with CAC. We observed women with presence of both BAC and CAC had the highest estimated 10-year risk of ASCVD: 18.54%, followed by presence of BAC but absence of CAC 11.65%, absence of BAC and presence of CAC 6.01%, and women with no BAC and no CAC presence had a mean 10-year risk of ASCVD of 5.25%. Conclusions: These findings support the value of BAC in identifying women at potentially increased risk of future cardiovascular disease without additional cost and radiation exposure.

Abstract P664: Proteomic Profiling of African-Ancestry Adults Identifies Potential Novel Biomarkers of Vascular Aging

During the aging process, the vasculature undergoes pathologic changes which are strongly associated with hypertension and future cardiovascular disease (CVD) risk. Previous work to identify protein biomarkers of these subclinical vascular changes, which have largely focused on single proteins, has observed many associations in different populations. However, research in African-ancestry populations, who are at high risk for hypertensive CVD, is limited and may be biased by the existing research in Whites. Therefore, we used a proteomic approach to identify biomarkers of vascular aging as assessed by pulse-wave velocity (PWV) and abdominal aortic calcification (AAC). We included 346 African-ancestry men from the Tobago Health Study, a prospective cohort study of community-dwelling men aged ≥40 years residing on the Caribbean island of Tobago. These men were aged from 53-89 years old (mean ± SD = 63.4 ± 8.1 years) and were overweight on average (mean ± SD BMI = 27.7 ± 4.3kg/m2). 79.2% of men had hypertension, 24.6% had diabetes, and 5.9% were current smokers. We quantified protein expression using the Olink® Target 96 Cardiovascular III proteomics panel which includes 92 proteins with known association to human cardiovascular processes (CVDIII; Olink®, Waltham, MA). Brachial-ankle PWV (cm/s) was measured using an automated waveform analyzer. AAC was measured in the aorta at the iliac bifurcation via CT and scored using the Agatston method. Partial Spearman correlations were calculated to assess the relationship between each protein biomarker and both vascular aging outcomes adjusting for age, Olink® assay batch, height, weight, diabetes status, hypertension status, and current smoking. There were 13 and 5 proteins correlated with PWV and AAC, respectively (at P&lt;0.05). All correlations were in the direct direction of effect. Only one protein, cystatin B, was correlated with both PWV and AAC (r= 0.17 and 0.12, P=0.002 and 0.03; respectively). After applying false discovery rate adjustment for multiple comparisons, only fatty acid binding protein 4 (FABP4) and PWV remained significant (r=0.18, P=0.046). In general, proteins categorized by Olink® as belonging to the inflammatory pathway were most likely to be correlated with PWV; whereas, those in the hormone response pathway were most frequently correlated with AAC. Our results highlight that FABP4, a protein related to atherosclerosis via inflammation, may also be an important marker of arterial stiffening in these African-ancestry men. Additionally, we identified cystatin B, a member of the cathepsin protease pathway, as a strong correlate of both PWV and AAC, which may warrant further research into it as a novel biomarker of vascular aging and CVD in this high-risk population. In conclusion, proteomics may be an effective tool for evaluating and identifying novel markers of vascular aging and CVD in underrepresented populations.

Abstract 14: Infant Gut Microbiome is Associated With Child Blood Pressure at Age 3 and 6 Years: Findings From a Danish Birth Cohort

Background: Experimental germ-free mice studies indicate that the gut microbiome affects blood pressure (BP). To our knowledge, no epidemiologic studies have investigated whether childhood BP, which portends future cardiovascular disease risk, is influenced by the infant gut microbiome—a microbiome that is less confounded by lifestyle. Understanding the link between gut microbiome and BP will shed light on gut microbiome as a modifiable way to improve child cardiovascular health. Objectives: To examine prospective associations of the gut microbiome at 1 month and 1 year with systolic BP (SBP) at 3 and 6 years, and to examine if the associations differed by breastfeeding duration over infancy. Methods: We used data from children followed up from birth to six years of age in the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort in Denmark. We measured infant gut microbiome at 1mo and 1y by 16S rRNA sequencing (V4 region). Research staff measured child BP in triplicate using standardized protocols during scheduled study visits at 3y and 6y. We analyzed microbiome features at each time point during infancy in relation to SBP at 3y and 6y, separately. We focused on Shannon index as a measure of microbiome alpha diversity, and differential abundance of microbial taxa. We assessed effect measure modification by breastfeeding duration at time of microbiome measurement. We adjusted models for maternal diet score during pregnancy, preeclampsia, gestational age, birth weight, and breastfeeding duration (when it was not a modifier). Results: Of 526 children included in the analysis, 49% were female and 78% were born vaginally. A 1-unit increment in Shannon index at 1mo was associated with -0.35 mmHg (-1.61, 0.91) lower SBP at 3y and -1.21 (-2.20, -0.23) lower SBP at 6y. Lower abundance of Bacteroides and higher abundance of Staphylococcus at 1mo was associated with higher SBP at 3y only (both FDR-P &lt;0.05); no microbial taxa at 1mo were significantly associated with SBP at 6y. As for microbiome at 1y, associations differed by breastfeeding duration ( P-interaction &lt; 0.10). In children who were breastfed beyond 1y, a 1-unit increment in Shannon index at 1y was associated with -2.94 mmHg (-5.59, -0.28) and -1.02 mmHg (-3.24, 1.19) lower SBP at 3y (n=56) and 6y (n=72), respectively. In contrast, in children who were breastfed shorter than 1y, 1-unit increment in Shannon index was associated with 0.55 (-0.75, 1.85) and 1.26 (0.28, 2.24) higher SBP at 3y (n=298) and 6y (n=382), respectively. After multivariable adjustment, no microbial taxa at 1y were significantly associated with SBP at 3y or 6y. Conclusions: Higher gut microbiome Shannon diversity and higher Bacteroides and lower Staphylococcus at 1 month was prospectively associated with higher child BP at 3 and 6 years of age. Microbiome Shannon diversity at 1 year was also associated with child BP, however, associations depended on breastfeeding.

Abstract MP60: Prediabetes and Undiagnosed Diabetes Predisposing Women to Excess Risk of Cardiovascular Disease

Objective: Women with type 2 diabetes (T2DM) have a 25-50% higher risk of cardiovascular disease (CVD) than their men counterparts. The reasons for this sex disparity are incompletely understood. We sought to examine if pre-diabetes (preDM) and undiagnosed T2DM are associated with a greater magnitude of CVD risk in women than in men. Methods: We pooled CVD-free individuals (N=18,745) from the Atherosclerosis Risk in Communities, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. CVD outcomes included incident coronary heart disease (CHD) (myocardial infarction, CHD death, or cardiac procedures including percutaneous coronary interventions, bypass surgery, or coronary revascularization), stroke (ischemic or hemorrhagic stroke), and a composite atherosclerotic CVD (ASCVD) (any CHD condition or stroke). Multivariable Cox models examined the outcomes associated with preDM (fasting glucose [FG] 100-125 mg/dL or HbA1c 5.7-6.4%) or undiagnosed T2DM (FG ≥126 mg/dL or HbA1c ≥6.5% and without a DM diagnosis or anti-diabetes medication use) adjusted for age, race/ethnicity, education, BMI, blood pressure, total cholesterols, smoking, anti-hypertensive and lipid-lowering medications, and cohort indicator. An interaction term sex x preDM or undiagnosed DM was added to models to test the sex modifying effect. We consider p-interaction&lt;0.2 as significant. Results: During a median follow-up of 17 years, the adjusted model showed that preDM was significantly associated with a higher risk of CHD (Hazard ratio 1.09, 95%CI 1.04-1.14), stroke (1.08, 1.04-1.13), and ASCVD (1.09, 1.04-1.14) in women, but not in men (1.04, 0.99-1.1 for CHD, 1.03, 0.98-1.08 for stroke, and 1.03, 0.98-1.09 for ASCVD, respectively). Undiagnosed T2DM was significantly associated with the risk of CHD (1.27, 1.16-1.4 in women and 1.17, 1.05-1.3 in men), stroke (1.32, 1.21-1.45 in women and 1.2, 1.09-1.32 in men), and ASCVD (1.27, 1.16-1.4 in women and 1.15, 1.03-1.29 in men) in both sexes but with more pronounced effect in women (P-interactions ≤0.11). In racial-stratified analysis, a higher magnitude of CVD risk associated with preDM or undiagnosed DM was also found in non-Hispanic (NH) white women and NH-black women than in their men counterparts. Conclusions: PreDM and undiagnosed DM predispose women to excess CVD risk, possibly due to women’s higher susceptibility to metabolic dysfunction at a lower glucose level and the prolonged unmanaged time for risk factors relative to men. T2DM screening and risk factor control should be enhanced in both sexes to reduce future CVD risk, particularly in women.

Risk of Target Organ Damage in Children With Primary Ambulatory Hypertension: A Systematic Review and Meta-Analysis.

Target organ damage (TOD) such as left ventricular hypertrophy (LVH), abnormal pulse wave velocity, and elevated carotid intima-media thickness are common among adults with hypertension and are associated with overt cardiovascular events. The risk of TOD among children and adolescents with hypertension confirmed by ambulatory blood pressure monitoring is poorly understood. In this systematic review, we compare the risks of TOD among children and adolescents with ambulatory hypertension to normotensive individuals. A literature search was conducted to include all relevant English-language publications from January 1974 to March 2021. Studies were included if patients underwent 24-hour ambulatory blood pressure monitoring and ≥1 TOD was reported. Ambulatory hypertension was defined by society guidelines. Primary outcome was the risk of TOD, including LVH, left ventricular mass index, pulse wave velocity, and carotid intima-media thickness among children with ambulatory hypertension compared with those with ambulatory normotension. Meta-regression calculated the effect of body mass index on TOD. Of 12 252 studies, 38 (n=3609 individuals) were included for analysis. Children with ambulatory hypertension had an increased risk of LVH (odds ratio, 4.69 [95% CI, 2.69-8.19]), elevated left ventricular mass index (pooled difference, 5.13 g/m2.7; [95% CI, 3.78-6.49]), elevated pulse wave velocity (pooled difference, 0.39 m/s [95% CI, 0.20-0.58]), and elevated carotid intima-media thickness (pooled difference, 0.04 mm [95% CI, 0.02-0.05]), compared with normotensive children. Meta-regression showed a significant positive effect of body mass index on left ventricular mass index and carotid intima-media thickness. Children with ambulatory hypertension have adverse TOD profiles, which may increase their risk for future cardiovascular disease. This review highlights the importance of optimizing blood pressure control and screening for TOD in children with ambulatory hypertension. URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42020189359.

Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease

The findings of this study provide genetic evidence supporting an association between HDPs and higher risk of coronary artery disease and stroke, which is only partially mediated by cardiometabolic factors. This supports classification of HDPs as risk factors for cardiovascular disease. A genome-wide genetic association study using mendelian randomization (MR) was performed from February 16 to March 4, 2022. Primary analysis was conducted using inverse-variance-weighted MR. Mediation analyses were performed using a multivariable MR framework. All studies included patients predominantly of European ancestry. Female-specific summary-level data from FinnGen (sixth release). Uncorrelated (r2<0.001) single-nucleotide variants (SNVs) were selected as instrumental variants from the FinnGen consortium summary statistics for exposures of any HDP, gestational hypertension, and preeclampsia or eclampsia. Hypertensive disorders in pregnancy (HDPs) are major causes of maternal and fetal morbidity and are observationally associated with future maternal risk of cardiovascular disease. However, observational results may be subject to residual confounding and bias. Genetic association estimates for outcomes were extracted from genome-wide association studies of 122 733 cases for coronary artery disease, 34 217 cases for ischemic stroke, 47 309 cases for heart failure, and 60 620 cases for atrial fibrillation. To investigate the association of HDPs with multiple cardiovascular diseases. Genetically predicted HDPs were associated with a higher risk of coronary artery disease (odds ratio [OR], 1.24; 95% CI, 1.08-1.43; P = .002); this association was evident for both gestational hypertension (OR, 1.08; 95% CI, 1.00-1.17; P = .04) and preeclampsia/eclampsia (OR, 1.06; 95% CI, 1.01-1.12; P = .03). Genetically predicted HDPs were also associated with a higher risk of ischemic stroke (OR, 1.27; 95% CI, 1.12-1.44; P = 2.87 × 10-4). Mediation analysis revealed a partial attenuation of the effect of HDPs on coronary artery disease after adjustment for systolic blood pressure (total effect OR, 1.24; direct effect OR, 1.10; 95% CI, 1.02-1.08; P = .02) and type 2 diabetes (total effect OR, 1.24; direct effect OR, 1.16; 95% CI, 1.04-1.29; P = .008). No associations were noted between genetically predicted HDPs and heart failure (OR, 0.97; 95% CI, 0.76-1.23; P = .79) or atrial fibrillation (OR, 1.11; 95% CI, 0.65-1.88; P = .71).

Arterial Stiffness as a Predictor of the Index of Atherosclerotic Cardiovascular Disease in Hypertensive Patients.

The aim of this study was to evaluate the predictive value of carotid-femoral pulse wave velocity (cfPWV) and cardiovascular disease in the hypertensive population in China and to determine the specific cfPWV cut-off value for assessing future cardiovascular disease (CVD) risk. This cross-sectional study included 630 hospital patients with primary hypertension and multiple cardiovascular risk factors or complications involving damage to clinical target organs. The study was conducted between July 2007 and October 2008. Atherosclerotic cardiovascular disease (ASCVD) risk calculations were computed according to criteria presented by the American College of Cardiology and the American Heart Association. Patients were stratified by a predefined risk threshold of 10% and divided into two groups: ASCVD ≥ 10% or ASCVD < 10%. cfPWV was used as a marker of arterial stiffness. A receiver operating characteristics (ROC) curve was applied to establish the optimal cfPWV cut-off point to differentiate between participants with and without ASCVD risk. In the study cohort of 630 patients (age 63.55.2 ± 8.6 years, 61.7% male) with primary hypertension, the pressure indices (augmented pressure, augmentation index [AIx], aortic pulse pressure, aortic systolic pressure [SBP]) and Framingham Risk Scores (FRS) were greater in females than in males (p < 0.001); ASCVD risk scores and peripheral diastolic pressure (DBP) were higher in males (p < 0.05). All hemodynamic indices showed a significant positive correlation with ASCVD risk scores and FRS; AIx was not correlated with ASCVD risk scores. In multivariate logistic analysis, cfPWV was significantly associated with ASCVD risk (OR: 1.324, 95% confidence interval: 1.119-1.565, p < 0.001) after adjusting for age, gender, smoking, body mass index, total cholesterol, fasting blood glucose, antihypertensive treatment, statin treatment, and DBP. In the ROC analysis, the area under the curve was 0.758 and 0.672 for cfPWV and aortic SBP (p < 0.001 and p < 0.001, respectively); the optimal critical value of cfPWV and aortic SBP was 12.45 m/s (sensitivity 63.2%, specificity 77.8%) and 124.5 mmHg (sensitivity 63.9%, specificity 65.3%). cfPWV is significantly correlated with the risk of ASCVD. The best cut-off value of cfPWV for assessing future CVD risk in the hypertensive population in China is 12.45 m/s.

The Prolonged Effect of Shift Work and the Impact of Reducing the Number of Nightshifts on Arterial Stiffness-A 4-Year Follow-Up Study.

To assess changes in blood pressure (BP) and arterial stiffness among 84 rotating shift and 25 dayworkers (control subjects) at two industrial plants during a 4-year follow-up, and to assess changes in outcome variables among shift workers at the two plants after a reduction in the number of night shifts during the last year of follow-up in one of the plants. We collected demographic data using a questionnaire, examined systolic and diastolic blood pressure (sBP, dBP), central systolic and diastolic aorta pressure (cSP, cDP), augmentation pressure (AP), central pulse pressure (cPP), and pulse wave velocity (PWV). We registered sleep quality. The last 4-14 months of follow-up one plant implemented a 12-week shift plan reducing the total number of night shifts and consecutive night shifts from 16.8 to 14 and from 7.2 to 4. To assess differences in change of outcomes between study groups we applied linear mixed models. The dayworkers were older, more hypertensive, reported less sleep disturbance, and smoked/snuffed less than the shift workers did. The adjusted annual increase in PWV was 0.34 m/s (95%CI, 0.22, 0.46) among shift workers and 0.09 m/s (95%CI, -0.05, 0.23) in dayworkers, yielding a significant difference of change of 0.25 m/s (95%CI, 0.06, 0.43). No significant differences were found between the two groups of shift workers in any cardiovascular disease (CVD) outcome during the last year of follow-up. Shift work in industry is associated with arterial stiffness, reflecting an increased risk of future CVD. No significant changes in arterial stiffness were identified as a consequence of a small reduction in the number of night shifts and consecutive night shifts.

Worsened Stroke Outcome in a Model of Preeclampsia is Associated With Poor Collateral Flow and Oxidative Stress.

Preeclampsia increases the incidence of maternal stroke, a devastating condition that is on the rise. We investigated stroke outcome in a model of experimental preeclampsia with and without treatment with clinically relevant doses of magnesium sulfate (experimental preeclampsia+MgSO4) compared to normal late-pregnant and nonpregnant rats. Transient middle cerebral artery occlusion was used to induce focal stroke for either 1.5 or 3 hours. Infarct volume and hemorrhagic transformation were determined as measures of stroke outcome. Changes in core middle cerebral artery and collateral flow were measured by dual laser Doppler. The relationship between middle cerebral artery perfusion deficit and infarction was used as a measure of ischemic tolerance. Oxidative stress and endothelial dysfunction were measured by 3-nitrotyrosine and 8-isoprostane, in brain and serum, respectively. Late-pregnant animals had robust collateral flow and greater ischemic tolerance of brain tissue, whereas experimental preeclampsia had greater infarction that was related to poor collateral flow, endothelial dysfunction, and oxidative stress. Importantly, pregnancy appeared preventative of hemorrhagic transformation as it occurred only in nonpregnant animals. MgSO4 did not provide benefit to experimental preeclampsia animals for infarction. Stroke outcome was worse in a model of preeclampsia. As preeclampsia increases the risk of future stroke and cardiovascular disease, it is worth understanding the influence of preeclampsia on the material brain and factors that might potentiate injury both during the index pregnancy and years postpartum.

Development and Validation of a Nomogram to Predict the Future Risk of Cardiovascular Disease.

Early identification of individuals at a high risk of cardiovascular disease (CVD) is crucial. This study aimed to construct a nomogram for CVD risk prediction in the general population. This retrospective study analyzed the data between January 2012 and September 2020 at the Physical Examination Center of the Second Affiliated Hospital of Nanjing Medical University (randomized 7:3 to the training and validation cohorts). The outcome was the occurrence of CVD events, which were defined as sudden cardiac death or any death related to myocardial infarction, acute exacerbation of heart failure, or stroke. The least absolute shrinkage and selection operator (LASSO) method and multivariate logistic regression were applied to screen the significant variables related to CVD. Among the 537 patients, 54 had CVD (10.1%). The median cardiac myosin-binding protein-C (cMyBP-C) level in the CVD group was higher than in the no-CVD group (42.25 pg/mL VS 25.00 pg/mL, p = 0.001). After LASSO selection and multivariable analysis, cMyBP-C (Odds ratio [OR] = 1.004, 95% CI [CI, confidence interval]: 1.000-1.008, p = 0.035), age (OR = 1.023, 95% CI: 0.999-1.048, p = 0.062), diastolic blood pressure (OR = 1.025, 95% CI: 0.995-1.058, p = 0.103), cigarettes per day (OR = 1.066, 95% CI: 1.021-1.113, p = 0.003), and family history of CVD (OR = 2.219, 95% CI: 1.003-4.893, p = 0.047) were associated with future CVD events (p 0.200). The model, including cMyBP-C, age, diastolic blood pressure, cigarettes per day, and family history of CVD, displayed a high predictive ability with an area under the curve (AUC) of 0.816 (95% CI: 0.714-0.918) in the training cohort (specificity and negative predictive value of 0.92 and 0.96) and 0.774 (95% CI: 0.703-0.845) in the validation cohort. A nomogram based on cMyBP-C, age, diastolic blood pressure, cigarettes per day, and family history of CVD was constructed. The model displayed a high predictive ability.