Risk Of Future Cardiovascular Disease Research Articles

Treatment drop-in in a contemporary cohort used to derive cardiovascular risk prediction equations

BackgroundNo routinely recommended cardiovascular disease (CVD) risk prediction equations have adjusted for CVD preventive medications initiated during follow-up (treatment drop-in) in their derivation cohorts. This will lead to underestimation of...

The relationship of health activation with risk of future cardiovascular disease among rural family caregivers of patients with chronic illnesses.

Family caregivers are at higher risk for developing cardiovascular disease (CVD) than non-caregivers. This risk is worse for those who live in rural compared to urban areas. Health activation, an indicator of engagement in self-care, is predictive of health outcomes and CVD risk in several populations. However, it is not known whether health activation is associated with CVD risk in rural caregivers of patients with chronic illnesses nor is it clear whether sex moderates any association. Our aims were to determine (1) whether health activation independently predicts 10-year CVD risk; and (2) whether sex interacts with health activation in the prediction of 10-year CVD risk among rural family caregivers (N=247) of patients with chronic illnesses. Health activation was measured using the Patient Activation Measure. The predicted 10-year risk of CVD was assessed using the Framingham Risk Score. Data were analyzed using nonlinear regression analysis. Higher levels of health activation were significantly associated with decreased risk of developing CVD (p<0.028). There was no interaction of sex with health activation on future CVD risk. However, male caregivers had greater risk of developing CVD in the next 10 years than female caregivers (p<0.001). We demonstrated the importance of health activation to future CVD risk in rural family caregivers of patients with chronic illnesses. We also demonstrated that despite the higher risk of future CVD among male, the degree of association between health activation and CVD risk did not differ by sex.

The Risk of Cardiovascular Disease Risk Among Adults with Vision Impairment from Low-, Middle- and High-Income Countries

ABSTRACT Purpose The limited evidence for cardiovascular disease (CVD) among adults with vision impairment (VI) has often been from developed countries using self-reported VI. This study evaluated the association of objectively-determined VI with the risk of CVD among adults from low-, middle-, and high-income countries. Methods Data were from 32,268 adults aged 30–74 years without CVD or blindness from China, Ghana, India, Mexico, Russian Federation, South Africa, and the United States during 2007–2010. VI and severe VI was defined as presenting visual acuity worse than 6/18, and 6/60, respectively. The Framingham risk algorithm was used to estimate the risk for incident CVD. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals. Results The mean age of participants was 46.4 years, with half of them being women (49.3%). The age-adjusted prevalence of VI ranged from 1.1% (United States) to 14.2% (South Africa) while severe VI ranged from 0.4% (United States) to 4.5% (Ghana). In models adjusting for country, sociodemographic factors, waist girth, healthcare use, activities of daily living and other health-related factors, VI was associated with CVD risk ≥ 10% (OR = 1.69, 95% CI: 1.22–2.36). This observed association was largely consistent across countries (p = 0.119). The observed CVD risk was similar among adults with moderate or severe VI (OR = 0.95, 95% CI: 0.50–1.83). CVD risk was higher among adults with VI who were <65 years old (OR = 1.89, 95% CI: 1.36–2.63) or were employed (OR = 2.24, 95% CI: 1.58–3.16). Conlusions This cross-national study shows that individuals with VI are at high risk for future CVD.

Are longitudinal changes in sleep patterns associated with future cardiovascular disease risk?

Are longitudinal changes in sleep patterns associated with future cardiovascular disease risk?

Left Atrial Mechanics Following Preeclamptic Pregnancy.

Preterm preeclampsia is a pregnancy complication associated with myocardial dysfunction and premature cardiovascular disease morbidity and mortality. Left atrial (LA) strain is a noninvasive index of left ventricular end diastolic pressure and an early marker of heart failure risk. This study aimed to evaluate LA strain during the postpartum period in participants with and without preterm preeclampsia and to assess whether this varied in the presence of hypertension, cardiac dysfunction or both. In this longitudinal cohort study, 321 women from 28 hospitals with preterm preeclampsia (cases) underwent cardiovascular assessment 6 months postpartum. This is a secondary analysis of the PHOEBE study (ISRCTN01879376). An uncomplicated pregnancy control group (n=30) was recruited from a single center for comparison. A full cross-sectional transthoracic echocardiogram was performed, and from these images, the myocardial strain of the left atrium, including reservoir, conduit, and contractile strain, as well as LA stiffness, were calculated. At 6 months postpartum, compared with controls, prior preeclampsia was associated with a significantly attenuated LA reservoir, conduit, and contractile strain, as well as increased LA stiffness (all P<0.001). LA strain was further reduced in preeclamptic women who had and had not developed hypertension, systolic, or diastolic dysfunction at 6 months postpartum (all P<0.05). LA mechanics were significantly attenuated at 6 months postpartum in participants with preterm preeclampsia, whether or not they remained hypertensive or had evidence of ventricular dysfunction. Further studies are needed to determine whether postnatal LA strain may identify women at greater risk for future cardiovascular disease.

The Role of Angiopoietins in Cardiovascular Outcomes of Kidney Transplant Recipients- An Ancillary Study From the FAVORIT.

Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD) mortality. We investigated vascular biomarkers, angiopoietin-1 and angiopoietin-2 (angpt-1, -2), in CVD development in KTRs. This ancillary study from the FAVORIT, evaluates the associations of baseline plasma angpt-1,-2 levels in CVD development (primary outcome) and graft failure (GF) and death (secondary outcomes) in 2000 deceased donor KTRs. We used Cox regression to analyze the association of biomarker quartiles with outcomes. We adjusted for demographic, CVD and transplant-related variables; medications; urine albumin-to-creatinine ratio and randomization status. We calculated areas under the curves (AUC) to predict CVD or death, and GF or death by incorporating biomarkers alongside clinical variables. Participants' median age was 52 IQR [45, 59] years: with 37% women and 73% identifying as white. Median time from transplantation was 3.99 IQR [1.58, 7.93] years and to CVD development was 2.54 IQR [1.11-3.80] years. Quartiles of angpt-1 were not associated with outcomes. Whereas higher levels of angpt-2 (quartile 4) were associated with about 2 times the risk of CVD, GF and death [aHR 1.85 (1.25 - 2.73), P<.01; 2.24 (1.36 - 3.70), P<.01; 2.30 (1.48 - 3.58), P<.01, respectively] as compared to quartile 1. Adding angiopoietins to pre-existing clinical variables improved prediction of CVD or death (AUC improved from 0.70 to 0.72, P=0.005) and GF or death (AUC improved from 0.68 to 0.70, P =0.005). Angpt-2 may partially explain the increased risk of future CVD in KTRs. Further research is needed to assess the utility of using angiopoietins in the clinical care of KTRs. Angpt-2 may be a useful prognostic tool for future CVD in KTRs. Combining angiopoietins with clinical markers may tailor follow-up to mitigate CVD risk.

Immune Activation Promotes Cardiac Remodeling in a Mouse Model of Takotsubo Cardiomyopathy

Takotsubo Cardiomyopathy (TCM) is an acute, life-threatening condition characterized by a drop in ejection fraction (EF) and apical ballooning of the left ventricle (LV). TCM is most frequently observed in women and is associated with an emotional or physical stressor. Importantly, with medical intervention, cardiac dysfunction is transient, and EF is often restored over weeks to months. Despite this, patients who experience TCM are at an increased risk of additional cardiovascular events and premature mortality. The precise etiology of TCM is unknown but a wave of excess circulating catecholamines is thought to be a trigger. Furthermore, the cause for increased cardiovascular risk post-TCM is unknown. The goal of this study is to understand how the immune system may contribute to TCM and the associated cardiovascular event risk. To induce TCM, mice were given a single dose of 200mg/kg isoproterenol (ISO), i.p. and cardiac function was assessed by conscious echocardiography (ECG). An initial study compared the effect of ISO between sexes (n=4-6). Though ISO induced a drop in EF in both sexes after 24 hours (p&lt;0.001 compared to vehicle (Veh)), females exhibited lower EF (46.64±3.11%) than males (68.36±2.62%, p&lt;0.0001). This mirrors the increased prevalence of clinically defined TCM in females in human populations. For this reason, female mice were used for the following experiments. A time course study demonstrated that EF begins to normalize by Day 3 (78.78±2.70 v 90.80±1.00%, p&lt;0.001) and is restored to baseline levels by Day 7 (90.65±1.17%). Flow cytometry was used to identify changes in immune cell populations in the heart on Days 0, 1, 3 and 7 (n=4-5). Neutrophils and inflammatory monocytes increased on Day 1, returning to baseline by Day 3. Dendritic cells and macrophages were elevated on Day 3 post-ISO, with a specific increase in CCR2+ TIM4- recruited inflammatory macrophages (p&lt;0.0001). Across all subsets, the number of immune cells returned to baseline levels by Day 7. Due to the robust immune response observed, we tested the specific hypothesis that transfer of immune cells from mice who have experienced TCM would induce cardiac dysfunction in naïve recipient mice. Donor mice were treated with either Veh or ISO and 1 day later splenocyte isolation and transfer was performed. Importantly, transfer of splenocytes from mice who had TCM induced a significant drop in EF the following day in the recipient mice (86.30±1.08%, p=0.001, n=10) concurrent with an increase in LV inner diameter and volume during systole. A final study tested the hypothesis that a history of TCM would increase risk for future cardiovascular disease. Veh or ISO-treated mice were allowed to recover for 10 days. Tail-cuff plethysmography showed no significant difference in baseline blood pressure and minipumps were implanted to deliver a constant infusion of Angiotensin II (Ang II, 140ng/kg/min). Mice with a history of TCM exhibited higher blood pressures compared to controls (135.11±3.32 v 116.9±6.41mmhg, n=6/9, p&lt;0.05) by week 2 of Ang II infusion. These results together demonstrated that TCM is associated with a robust immune response and points to a possible causal contribution of immune activation to the cardiac dysfunction observed in TCM. Furthermore, a history of TCM promotes a hypertensive phenotype, but additional studies are needed to test whether this is through immunological mechanisms. AHAPOST837441 DJF, 19EIA34480023-MSM, and 1R01 HL161212-MSM. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

ASSOCIATION OF BLOOD PRESSURE TRAJECTORIES SINCE YOUNG ADULTHOOD WITH CARDIOVASCULAR DISEASES IN LATER LIFE

Objective: To identify blood pressure (BP) trajectories since young adulthood and to determine their association with risk of cardiovascular diseases (CVD) in later life. Design and method: This cohort study used data of young adults aged 18 to 39 years from the Kailuan Cohort, a prospective longitudinal study of Chinese men and women. Using group-based trajectory modeling, distinct BP trajectories from 2006 to 2010 were identified for 5 BP traits (mid-BP, SBP, DBP, MAP, and PP). Main outcomes were incident CVD (coronary revascularization, myocardial infarction, heart failure, or stroke), which were collected until 31 December 2020. Cox proportional hazards regression models were used to estimate the associations between BP trajectories and the risk of incident CVD. Results: Of the 11 535 adults included in the study (mean [SD] age, 32.6 [5.1] years), 8708 (75.5%) were men. We identified 3 trajectories for all BP traits (except for PP, which was 2). Among them, the mid-BP trajectory distribution was 4566 individuals (39.6%) with low-increasing, 5996 (52.0%) with moderate-increasing, and 973 (8.4%) with high-stable. Compared with the mid-BP low-increasing trajectory group, individuals in the moderate-increasing and high-stable groups had higher risk of CVD (moderate: HR, 2.44; 95% CI, 1.47 to 4.06; high: HR, 3.82; 95% CI, 1.98 to 7.39) after adjusting for socio-demographics and cardiovascular risk factors, as well as the baseline mid-BP level. Results were consistent after additionally adjusting for cumulative mid-BP exposure during 2006 to 2010 (moderate: HR, 2.31; 95% CI, 1.41 to 3.79; high: HR, 3.18; 95% CI, 1.72 to 5.90). Besides, the increased CVD risk associated with higher trajectories were also significant for SBP, DBP, MAP, and PP, and remained robust through several sensitivity analyses, which included excluding those who ever used antihypertensive drugs during 2006 to 2010, excluding events within the first year of follow-up, and considering death as competing risk. Conclusions: Higher BP trajectories since early adulthood were associated with an increased risk of CVD in later life. Early detection of BP trajectories may assist in more accurate identification of individuals with high risk of future CVD.

Predictability of Cardiovascular Risk Scores for Carotid Atherosclerosis in Community-Dwelling Middle-Aged and Elderly Adults.

Background: The assessment of future risk of cardiovascular diseases (CVD) is strongly recommended for all asymptomatic adults without CVD history. Carotid atherosclerosis (CA) is a preclinical phenotype of CVDs. However, data on estimated future CVD risks with respect to preclinical atherosclerosis are limited. This community-based study aimed to assess the relationships between predicted CVD risks and CA. Methods: We enrolled 3908 subjects aged 40-74 years without CVD history and calculated their 10-year CVD risks using the Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE). Carotid plaque (CP) at the extracranial carotid arteries was determined by high-resolution B-mode ultrasonography and further classified into mild or advanced CA. Results: The means of FRS for CP-negative and mild and advanced CA were 9.0%, 14.4%, and 22.1%, respectively (p-value < 0.0001). The corresponding values for PCE score were 4.8%, 8.8%, and 15.0%, respectively (p-value < 0.0001). The odds ratios (ORs) of having CP per 5.0% increase in FRS and PCE score were 1.23 (95% CI, 1.19-1.28) and 1.36 (95% CI, 1.28-1.44), respectively. The corresponding values of having advanced CA were 1.24 (95% CI, 1.19-1.29) and 1.38 (95% CI, 1.30-1.48), respectively. Among the models of FRS or PCE plus other conventional CVD risk factors, the FRS + age model had the highest discrimination for the presence of CP (AUROC, 0.7533; 95% CI, 0.7375-0.7691) as well as for the presence of advanced CA (AUROC, 0.8034; 95% CI, 0.7835-0.8232). The calibration of the FRS + age models for the presences of CP and advanced CA was excellent (χ2 = 8.45 [p = 0.49] and 10.49 [p = 0.31], respectively). Conclusions: Estimated future CVD risks were significantly correlated with risks of having CA. Both FRS and PCE had good discrimination for the presences of CP and advanced CA.

Association Between Life's Essential 8 Cardiovascular Health Metrics With Cardiovascular Events in the Cardiovascular Disease Lifetime Risk Pooling Project.

The American Heart Association recently launched updated cardiovascular health metrics, termed Life's Essential 8 (LE8). Compared with Life's Simple 7 (LS7), the new approach added sleep health as an eighth metric and updated the remaining 7 health factors and behaviors. The association of the updated LE8 score with long-term cardiovascular disease (CVD) outcomes and death is unknown. We pooled individual-level data from 6 contemporary US-based cohorts from the Cardiovascular Lifetime Risk Pooling Project. Total LE8 score (0-100 points), LE8 score without sleep (0-100 points), and prior LS7 scores (0-14 points) were calculated separately. We used multivariable-adjusted Cox models to evaluate the association of LE8 with CVD, CVD subtypes, and all-cause mortality among younger, middle, and older adult participants. Net reclassification improvement analysis was used to measure the improvement in CVD risk classification with the addition of LS7 and LE8 recategorization based on score quartile rankings. Our sample consisted of 32 896 US adults (7836 [23.8%] Black; 14 941 [45.4%] men) followed for 642 000 person-years, of whom 9391 developed CVD events. Each 10-point higher overall LE8 score was associated with lower risk by 22% to 40% for CVD, 24% to 43% for congenital heart disease, 17% to 34% for stroke, 23% to 38% for heart failure, and 17% to 21% for all causes of mortality events across age strata. LE8 score provided more granular differentiation of the related CVD risk than LS7. Overall, 19.5% and 15.5% of the study participants were recategorized upward and downward based on LE8 versus LS7 categories, respectively, and the recategorization was significantly associated with CVD risk in addition to LS7 score. The addition of recategorization between LE8 and LS7 categories improved CVD risk reclassification across age groups (clinical net reclassification improvement, 0.06-0.12; P<0.01). These findings support the improved utility of the LE8 algorithm for assessing overall cardiovascular health and future CVD risk.

Reduced Alcohol Consumption and Major Adverse Cardiovascular Events Among Individuals With Previously High Alcohol Consumption

Cardiovascular benefits of mild to moderate alcohol consumption need to be validated in the context of behavioral changes. The benefits of reduced alcohol consumption among people who drink heavily across different subtypes of cardiovascular disease (CVD) are unclear. To investigate the association between reduced alcohol consumption and risk of major adverse cardiovascular events (MACEs) in individuals who drink heavily across different CVD subtypes. This cohort study analyzed data from the Korean National Health Insurance Service-Health Screening database and self-reported questionnaires. The nationally representative cohort comprised Korean citizens aged 40 to 79 years who had national health insurance coverage on December 31, 2002, and were included in the 2002 to 2003 National Health Screening Program. People who drank heavily who underwent serial health examinations over 2 consecutive periods (first period: 2005-2008; second period: 2009-2012) were included and analyzed between February and May 2023. Heavy drinking was defined as more than 4 drinks (56 g) per day or more than 14 drinks (196 g) per week for males and more than 3 drinks (42 g) per day or more than 7 drinks (98 g) per week for females. Habitual change in heavy alcohol consumption during the second health examination period. People who drank heavily at baseline were categorized into 2 groups according to changes in alcohol consumption during the second health examination period as sustained heavy drinking or reduced drinking. The primary outcome was the occurrence of MACEs, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death. Of the 21 011 participants with heavy alcohol consumption at baseline (18 963 males [90.3%]; mean [SD] age, 56.08 [6.16] years) included in the study, 14 220 (67.7%) sustained heavy drinking, whereas 6791 (32.2%) shifted to mild to moderate drinking. During the follow-up of 162 378 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACEs than the reduced drinking group (817 vs 675 per 100 000 person-years; log-rank P = .003). Reduced alcohol consumption was associated with a 23% lower risk of MACEs compared with sustained heavy drinking (propensity score matching hazard ratio [PSM HR], 0.77; 95% CI, 0.67-0.88). These benefits were mostly accounted for by a significant reduction in the incidence of angina (PSM HR, 0.70; 95% CI, 0.51-0.97) and ischemic stroke (PSM HR, 0.66; 95% CI, 0.51-0.86). The preventive attributes of reduced alcohol intake were consistently observed across various subgroups of participants. Results of this cohort study suggest that reducing alcohol consumption is associated with a decreased risk of future CVD, with the most pronounced benefits expected for angina and ischemic stroke.

Abstract 2227: Physical activity at breast cancer diagnosis and incident cardiovascular disease in the Pathways Study

Abstract Background: Breast cancer survivors are at increased risk of cardiovascular disease (CVD) compared to women without a history of breast cancer. Although cardiotoxic cancer treatments influence these risks, lifestyles that are associated with both breast cancer and CVD also contribute. With the number of breast cancer survivors expected to increase, a growing need exists to identify modifiable risk factors that protect against the development of CVD after diagnosis. Physical activity at breast cancer diagnosis is associated with lower cancer recurrence and mortality risk. However, associations between physical activity at diagnosis and incident CVD have yet to be investigated in detail. Methods: The Pathways Study is a prospective cohort study of 4,504 women who were members of Kaiser Permanente Northern California (KPNC) when diagnosed with first primary invasive breast cancer between 2005 and 2013. At enrollment, women self-reported their frequency, duration, and intensity of physical activities during the previous six months using the Arizona Activity Frequency Questionnaire. This information was used to dichotomize the women’s physical activity levels by the CDC’s Physical Activity Guidelines for Americans (≥ 150 minutes of moderate-to-vigorous physical activity per week vs less). CVD events were obtained from electronic health records as part of the Pathways Heart Study and were defined as post-diagnostic incidence of ischemic heart disease, heart failure, cardiomyopathy, and stroke. Deaths were documented through several sources, including the National Death Index. Women were followed until the first of disenrollment from the KPNC health plan, death, or December 31, 2021. Competing risk Cox regression models were used to estimate associations between meeting CDC physical activity guidelines and CVD. Results: In this cohort of breast cancer survivors, women who self-reported meeting physical activity guidelines at diagnosis experienced lower rates of post-diagnostic CVD events (8.6% vs 13.1%). After adjustment for socio-demographic factors, meeting physical activity guidelines remained associated with lower risk of CVD (HR: 0.78, 95% CI: 0.61, 0.98); this association appeared to be driven by reduced risk of heart failure (HR: 0.68, 95% CI: 0.50, 0.93) and cardiomyopathy (HR: 0.51, 95% CI: 0.28, 0.92). Approximately 15% of the CVD risk reduction in Pathways Study participants can be attributed to meeting physical activity guidelines (population attributable risk percent: 14.5%, 95% CI: 8%, 21%). Conclusions: Compared to women who did not meet CDC physical activity guidelines, women who reported meeting guidelines near the time of their breast cancer diagnosis had decreased risk of future CVD, including heart failure and cardiomyopathy. Future studies investigating changes in post-diagnostic physical activity patterns and CVD risk are warranted. Citation Format: Jacob K. Kresovich, Alicia R. Richards, Isaac J. Ergas, Cecile A. Laurent, Rikki Cannioto, Jamal S. Rana, Janise M. Roh, Catherine Thomsen, Salma Shariff-Marco, Eileen Rillamas-Sun, Richard K. Cheng, Song Yao, Christine B. Ambrosone, Lawrence H. Kushi, Heather Greenlee, Marilyn L. Kwan. Physical activity at breast cancer diagnosis and incident cardiovascular disease in the Pathways Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2227.

Abstract P111: Pre-Diagnostic Free Testosterone and Estradiol Influence Heart Failure Risk in Both Women and Men: A Prospective Cohort Study in the UK Biobank

Introduction: Heart failure (HF) is a highly fatal manifestation of many cardiovascular diseases (CVDs). Free testosterone and 17β-estradiol have been linked to future risk of CVD. However, their roles in the pathogenesis of HF in both men and women are unclear. Hypothesis: We investigated the associations between free testosterone and 17β-estradiol (unbound to sex hormone binding globulin), and future risk of HF in the UK Biobank. Methods: Multivariable Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of incident HF (first hospitalization) in relation to quartiles (Q) of free testosterone and 17β-estradiol, and potential confounders, while stratifying by sex and in women by menopausal status. Non-linear relationships were tested using cubic splines. Results: There were 180,712 men (5585 cases with free testosterone and 571 cases with 17β-estradiol), and 177,324 women (2858 cases with free testosterone and 314 with 17β-estradiol). Increased free testosterone was associated with decreased HF risk in both men (HR Q4 vs. Q1 =0.86, 95%CI: 0.79-0.94, p-trend continuous &lt;0.0001) and post-menopausal women (HR Q4 vs. Q1 =0.83, 95%CI: 0.73-0.95), with non-linear relationships. Additionally, 17β-estradiol was significantly associated with decreased HF risk among men (HR Q4 vs. Q1 =0.76, 95%CI: 0.59-0.98), but positively associated among pre-menopausal women (HR Q4 vs. Q1 =2.16, 95%CI: 1.11-4.18). Conclusions: In this large cohort free of CVD at baseline, we detected a significant protective association between free testosterone and new HF diagnosis among men. In women however, the association differed by menopausal status as increased free testosterone was associated with elevated risk of HF before menopause but not after menopause. Further, 17β-estradiol was associated to elevated HF risk among pre-menopausal women but not post-menopausal women and men. Our findings suggest that sex hormones influence the pathogenesis HF and may offer potential pathways for interventions.

Abstract MP14: Gestational Diabetes Mellitus, Circulating Metabolites, and Risk of Future Cardiovascular Disease in US Women

Introduction: Gestational diabetes mellitus (GDM) is associated with higher lifetime cardiovascular disease (CVD) risk in women, even without subsequent type 2 diabetes (T2D). Dysregulation of lipid and amino acid metabolism precedes CVD and has been associated with T2D in women with GDM history. However, the precise metabolic pathways contributing to the persistent CVD risk after GDM remain unknown. Hypothesis: A metabolomic signature of GDM history is associated with higher CVD risk. Methods: Using elastic net regression, we constructed a postpartum (24-72 hours after delivery) metabolomic signature of GDM using maternal plasma metabolomics data in the Boston Birth Cohort (BBC; 161 GDM; 1,178 non-GDM; 64% Black). The GDM signature was internally validated in the BBC using leave-one-out cross-validation and externally replicated in a subset of Nurses’ Health Study II (NHS2; 392 prior GDM; 2,326 no GDM; 98% White) with available postpartum (a median of 17.5 years after delivery) plasma metabolomics data. CVD was defined as a composite of coronary artery disease (CAD; coronary artery bypass grafting, myocardial infarction, and coronary death) and stroke. Cox proportional hazards model was used to examine associations between the GDM signature and incident CVD in both NHS2 and Nurses’ Health Study (NHS; no data on GDM history; 95% White). A genome-wide association study (GWAS) was conducted in NHS2 and NHS to identify genes implicated in the GDM signature. Results: The externally validated GDM signature consists of 44 metabolites (21 lipids, 10 amino acids, and others). Women with prior GDM had a higher signature score than those without in both BBC (p=2х10 -20 ) and NHS2 (p=0.004). In NHS2 (n=2,718), 97 CVD cases (17 cases in 392 women with prior GDM) were documented in 23 years of follow-up. The GDM signature was significantly associated with higher risk of CVD (HR = 1.31 [1.04-1.65] for per-SD increase in the signature score) and CAD (HR = 1.81 [1.30-2.52]) but not stroke (HR = 1.05 [0.76-1.45]) after adjusting for age, race, body mass index (BMI), blood pressure, baseline T2D, medication use, and lifestyle factors. The associations did not change after additionally adjusting for GDM history and incident T2D. The GDM signature mediated associations between GDM and CAD (5.7%; p=0.048) and CVD (4.4%; p=0.038). In NHS (n=4,469), 874 CVD cases were documented in 31 years of follow-up. The GDM signature was associated with incident CAD (adjusted HR = 1.18 [1.07-1.29]) but not CVD and stroke. In GWAS, we identified genetic loci harboring genes ( FADS1 , FADS2 , and SOX2-OT ) related to fatty acid metabolism, blood lipid levels, glycemic traits, BMI, and insomnia. Conclusions: We identified and validated a metabolomic signature associated with GDM history, which was associated an increased risk of future CVD, especially CAD. Ongoing work is underway to replicate these findings in other racial and ethnic groups.

Primary Prevention of Cardiovascular Disease in Women.

Cardiovascular disease (CVD) remains a leading cause of mortality in women, necessitating innovative primary prevention strategies. Contemporary guidelines on primary prevention of CVD highlight the increasing prevalence of CVD risk factors and emphasize the significance of female-specific risk enhancers that substantially augment the future risk of CVD. These risk factors occur throughout a woman's life cycle, such as hormonal contraception, hypertensive disorders of pregnancy, and menopause, all of which confer an added layer of risk in women beyond the conventional risk factors. Despite this, current methods may not fully capture the nuanced vulnerabilities in women that increase their risk of CVD. In this review, we highlight gender-specific risk enhancers and subsequent prevention as well as strategies to improve primary prevention of CVD in women.

Assessing breast arterial calcification in mammograms and its implications for atherosclerotic cardiovascular disease risk

PurposeBreast arterial calcifications (BAC) are incidentally observed on mammograms, yet their implications remain unclear. We investigated lifestyle, reproductive, and cardiovascular determinants of BAC in women undergoing mammography screening. Further, we investigated the relationship between BAC, coronary arterial calcifications (CAC) and estimated 10-year atherosclerotic cardiovascular (ASCVD) risk. MethodsIn this cross-sectional study, we obtained reproductive history and CVD risk factors from 215 women aged 18 or older who underwent mammography and cardiac computed tomographic angiography (CCTA) within a 2-year period between 2007 and 2017 at hospital. BAC was categorized as binary (present/absent) and semi-quantitatively (mild, moderate, severe). CAC was determined using the Agatston method and recorded as binary (present/absent). Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated, accounting for age as a confounding factor. ASCVD risk over a 10-year period was calculated using the Pooled Cohort Risk Equations. ResultsOlder age, systolic and diastolic blood pressures, higher parity, and younger age at first birth (≤28 years) were significantly associated with greater odds of BAC. Women with both BAC and CAC had the highest estimated 10-year risk of ASCVD (13.30 %). Those with only BAC (8.80 %), only CAC (5.80 %), and no BAC or CAC (4.40 %) had lower estimated 10-year risks of ASCVD. No association was detected between presence of BAC and CAC. ConclusionsThese findings support the hypothesis that BAC on a screening mammogram may help to identify women at potentially increased risk of future cardiovascular disease without additional cost and radiation exposure.

Fetal loss and long-term maternal morbidity and mortality: A systematic review and meta-analysis.

Evidence suggests common pathways between pregnancy losses and subsequent long-term maternal morbidity, rendering pregnancy complications an early chronic disease marker. There is a plethora of studies exploring associations between miscarriage and stillbirth with long-term adverse maternal health; however, these data are inconclusive. We systematically searched MEDLINE, EMBASE, AMED, BNI, CINAHL, and the Cochrane Library with relevant keywords and MeSH terms from inception to June 2023 (no language restrictions). We included studies exploring associations between stillbirth or miscarriage and incidence of cardiovascular, malignancy, mental health, other morbidities, and all-cause mortality in women without previous pregnancy loss. Studies reporting short-term morbidity (within a year of loss), case reports, letters, and animal studies were excluded. Study selection and data extraction were performed by 2 independent reviewers. Risk of bias was assessed using the Newcastle Ottawa Scale (NOS) and publication bias with funnel plots. Subgroup analysis explored the effect of recurrent losses on adverse outcomes. Statistical analysis was performed using an inverse variance random effects model and results are reported as risk ratios (RRs) with 95% confidence intervals (CIs) and prediction intervals (PIs) by combining the most adjusted RR, odds ratios (ORs) and hazard ratios (HRs) under the rare outcome assumption. We included 56 observational studies, including 45 in meta-analysis. There were 1,119,815 women who experienced pregnancy loss of whom 951,258 had a miscarriage and 168,557 stillbirth, compared with 11,965,574 women without previous loss. Women with a history of stillbirth had a greater risk of ischaemic heart disease (IHD) RR 1.56, 95% CI [1.30, 1.88]; p < 0.001, 95% PI [0.49 to 5.15]), cerebrovascular (RR 1.71, 95% CI [1.44, 2.03], p < 0.001, 95% PI [1.92, 2.42]), and any circulatory/cardiovascular disease (RR 1.86, 95% CI [1.01, 3.45], p = 0.05, 95% PI [0.74, 4.10]) compared with women without pregnancy loss. There was no evidence of increased risk of cardiovascular disease (IHD: RR 1.11, 95% CI [0.98, 1.27], 95% PI [0.46, 2.76] or cerebrovascular: RR 1.01, 95% CI [0.85, 1.21]) in women experiencing a miscarriage. Only women with a previous stillbirth were more likely to develop type 2 diabetes mellitus (T2DM) (RR: 1.16, 95% CI [1.07 to 2.26]; p < 0.001, 95% PI [1.05, 1.35]). Women with a stillbirth history had an increased risk of developing renal morbidities (RR 1.97, 95% CI [1.51, 2.57], p < 0.001, 95% [1.06, 4.72]) compared with controls. Women with a history of stillbirth had lower risk of breast cancer (RR: 0.80, 95% CI [0.67, 0.96], p-0.02, 95% PI [0.72, 0.93]). There was no evidence of altered risk of other malignancies in women experiencing pregnancy loss compared to controls. There was no evidence of long-term mental illness risk in women with previous pregnancy losses (stillbirth: RR 1.90, 95% CI [0.93, 3.88], 95% PI [0.34, 9.51], miscarriage: RR 1.78, 95% CI [0.88, 3.63], 95% PI [1.13, 4.16]). The main limitations include the potential for confounding due to use of aggregated data with variable degrees of adjustment. Our results suggest that women with a history of stillbirth have a greater risk of future cardiovascular disease, T2DM, and renal morbidities. Women experiencing miscarriages, single or multiple, do not seem to have an altered risk.

Carotid wave analysis in young adults with a history of adolescent anorexia nervosa: a case control study

BackgroundAnorexia nervosa (AN) is associated with abnormalities that may increase the risk of future cardiovascular disease. This study assessed the cardiovascular health of individuals who recovered from AN during adolescence by conducting wave power analysis.MethodsFormer AN patients discharged from the Royal Children’s and Monash Children’s Hospitals (N = 17) in Melbourne, Australia underwent ultrasound imaging of the right carotid artery. Wave power analysis was conducted to assess biomechanical interactions of the cardiovascular system. Patient measures were compared to healthy controls (N = 51).ResultsEighty-eight percent of the former AN patients and controls were female, aged approximately 25 years, with a healthy body mass index. Mean carotid flow and pulsatility index were not different between groups. Carotid arterial strain and distensibility were lower, and the wave speed and beta stiffness index higher in the former AN patients. Characteristic impedance was not different nor were the forward and backward wave amplitudes. However, wave reflection indices (ratios of backward-to-forward compression wave area, and wave-related effect on pressure and hydraulic power) were 12–18% lower in the former AN patients (p < 0.05).ConclusionsIncreased carotid artery stiffness and reduced wave reflection are evident in young adults who recovered from adolescent AN. This may relate to an adaptive process that helps to maintain or restore flow and characteristic impedance despite increased vessel stiffness, with this warranting future investigation.

Temporary relationship between sleep duration and depression and its impact on future risk of cardiovascular disease

BackgroundAlthough sleep duration and depression were correlated, their temporal sequence and how the sequence influence on future risk of cardiovascular disease (CVD) remained undetermined. This study aimed to explore the temporal relationship between sleep duration and depression, and its association with future CVD risk. MethodsWe included 10,629 middle-aged and elderly participants with repeated measurements of sleep duration and depressive symptoms (measured by Center for Epidemiological Studies-Depression scale [CESD]) at the first two visits from the China Health and Retirement Longitudinal Study. Cross-lagged analysis and mediation analysis were used to examine the temporal relationship between sleep duration and depression and its impact on future risk of CVD. ResultsThe adjusted cross-lagged path coefficient from baseline sleep duration to follow-up CES-D (β1 = −0.191; 95 % confidence interval [CI], −0.239 to −0.142) was significantly greatly than that from baseline CES-D to follow-up sleep duration (β2 = −0.031; 95 % CI, −0.031 to −0.024) (Pdifference < 0.0001). Similarly, the path coefficient from baseline sleep duration to annual changes in CES-D was significantly greater than that from baseline CES-D to annual changes in sleep duration (β1 = −0.093 versus β2 = −0.015, Pdifference < 0.0001). The path coefficient from baseline sleep duration to follow-up CES-D in CVD group was significantly greater than that in those without CVD (Pdifference of β1 = 0.0378). Furthermore, 27.93 % of the total association of sleep duration with CVD was mediated by depression symptoms. ConclusionsThe findings provide evidence that decrease in sleep duration probably precedes the increased in depressive symptoms, and depression partially mediated the pathway from sleep duration to incident 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