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  1. Wang MC, Freaney PM, Perak AM, Greenland P, Lloyd-Jones DM, Grobman WA, et al.
    J Am Heart Assoc, 2021 09 07;10(17):e020717.
    PMID: 34431359 DOI: 10.1161/JAHA.120.020717
    Background The prevalence of obesity in the population has increased in parallel with increasing rates of adverse pregnancy outcomes (APOs). Quantifying contemporary trends in prepregnancy obesity and associations with interrelated APOs (preterm birth, low birth weight, and pregnancy-associated hypertension) together and individually can inform prevention strategies to optimize cardiometabolic health in women and offspring. Methods and Results We performed a serial, cross-sectional study using National Center for Health Statistics birth certificate data including women aged 15 to 44 years with live singleton births between 2013 and 2018, stratified by race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, and non-Hispanic Asian). We quantified the annual prevalence of prepregnancy obesity (body mass index ≥30.0 kg/m2; body mass index ≥27.5 kg/m2 if non-Hispanic Asian). We then estimated adjusted associations using multivariable logistic regression (odds ratios and population attributable fractions) for obesity-related APOs compared with normal body mass index (18.5-24.9 kg/m2; 18.5-22.9 kg/m2 if non-Hispanic Asian). Among 20 139 891 women, the prevalence of prepregnancy obesity increased between 2013 and 2018: non-Hispanic White (21.6%-24.8%), non-Hispanic Black (32.5%-36.2%), Hispanic (26.0%-30.5%), and non-Hispanic Asian (15.3%-18.6%) women (P-trend 
  2. Connolly SD, Lloyd-Jones DM, Ning H, Marino BS, Pool LR, Perak AM
    J Am Heart Assoc, 2022 Nov 15;11(22):e026797.
    PMID: 36370007 DOI: 10.1161/JAHA.122.026797
    Background Cardiovascular health (CVH) is suboptimal in US adolescents. Social determinants of health (SDOH) may affect CVH. We examined SDOH by race and ethnicity and assessed for associations between SDOH and CVH among US adolescents. Methods and Results We analyzed data from the National Health and Nutrition Examination Survey for 3590 participants aged 12 to 19 years from 1999 to 2014. SDOH variables were chosen and an SDOH score assigned (range, 0-7 points; higher=more favorable). CVH was classified according to American Heart Association criteria. We estimated population prevalence and used multivariable linear and polytomous logistic regression for associations between SDOH and CVH. SDOH varied by group, with the non-Hispanic White group (n=1155) having a higher/better mean SDOH score compared with non-Hispanic Black (n=1223) and Mexican American groups (n=1212). Associations between SDOH and CVH differed between racial and ethnic groups (interaction P<0.0001). For the non-Hispanic White group, each additional favorable SDOH variable was associated with a CVH score higher/better by 0.3 points (β, 0.3, P<0.0001), 20% higher odds for moderate (versus low) CVH (odds ratio [OR], 1.2 [95% CI, 1.1-1.4]), and 80% higher odds for high/favorable (versus low) CVH (1.8 [1.5-2.1]). Associations between SDOH and CVH were more modest among the Mexican American group (β, 0.12, P=0.001; OR 1.1 [1.0-1.2] for moderate CVH; OR, 1.3 [1.1-1.6] for high CVH) and were not significant among the non-Hispanic Black group (β, 0.07; P=0.464). Conclusions SDOH and CVH were more favorable for non-Hispanic White adolescents compared with non-Hispanic Black and Mexican American adolescents. SDOH were strongly associated with CVH among the non-Hispanic White group. Racially and culturally sensitive public policy approaches may improve CVH in US adolescents.
  3. Perak AM, Ning H, Khan SS, Van Horn LV, Grobman WA, Lloyd-Jones DM
    J Am Heart Assoc, 2020 Feb 18;9(4):e015123.
    PMID: 32063122 DOI: 10.1161/JAHA.119.015123
    Background Pregnancy is a cardiometabolic stressor and thus a critical period to address women's lifetime cardiovascular health (CVH). However, CVH among US pregnant women has not been characterized. Methods and Results We analyzed cross-sectional data from National Health and Nutrition Examination Surveys 1999 to 2014 for 1117 pregnant and 8200 nonpregnant women, aged 20 to 44 years. We assessed 7 CVH metrics using American Heart Association definitions modified for pregnancy; categorized metrics as ideal, intermediate, or poor; assigned these categories 2, 1, or 0 points, respectively; and summed across the 7 metrics for a total score of 0 to 14 points. Total scores 12 to 14 indicated high CVH; 8 to 11, moderate CVH; and 0 to 7, low CVH. We applied survey weights to generate US population-level estimates of CVH levels and compared pregnant and nonpregnant women using demographic-adjusted polytomous logistic and linear regression. Among pregnant women, the prevalences (95% CIs) of ideal levels of CVH metrics were 0.1% (0%-0.3%) for diet, 27.3% (22.2%-32.3%) for physical activity, 38.9% (33.7%-44.0%) for total cholesterol, 51.1% (46.0%-56.2%) for body mass index, 77.7% (73.3%-82.2%) for smoking, 90.4% (87.5%-93.3%) for blood pressure, and 91.6% (88.3%-94.9%) for fasting glucose. The mean total CVH score was 8.3 (95% CI, 8.0-8.7) of 14, with high CVH in 4.6% (95% CI, 0.5%-8.8%), moderate CVH in 60.6% (95% CI, 52.3%-68.9%), and low CVH in 34.8% (95% CI, 26.4%-43.2%). CVH levels were significantly lower among pregnant versus nonpregnant women; for example, 13.0% (95% CI, 11.0%-15.0%) of nonpregnant women had high CVH (adjusted, comparison P=0.01). Conclusions From 1999 to 2014, <1 in 10 US pregnant women, aged 20 to 44 years, had high CVH.
  4. Colangelo LA, Carroll AJ, Perak AM, Gidding SS, Lima JAC, Lloyd-Jones DM
    Psychosom Med, 2024 01 09;86(2):60-71.
    PMID: 38193784 DOI: 10.1097/PSY.0000000000001277
    OBJECTIVE: Depression is a risk factor for coronary heart disease and left ventricular hypertrophy (LVH) is a potent predictor of coronary heart disease events. Whether depression is associated with LVH has received limited investigation. This study assessed cross-sectional and 20-year longitudinal associations of depressive symptoms with LVH outcomes after accounting for important known confounders.

    METHODS: From 5115 participants enrolled in 1985-1986 in the Coronary Artery Risk Development in Young Adults Study, 2533 had serial measures of depressive symptoms and subsequent echocardiography to measure normal LV geometry, concentric remodeling, and LVH. The primary exposure variable was trajectories of the Center for Epidemiologic Studies Depression (CES-D) scale score from 1990-1991 to 2010-2011. Multivariable polytomous logistic regression was used to assess associations of trajectories with a composite LV geometry outcome created using echocardiogram data measured in 2010-2011 and 2015-2016. Sex-specific conflicting results led to exploratory models that examined potential importance of testosterone and sex hormone-binding globulin.

    RESULTS: Overall CES-D and Somatic subscale trajectories had significant associations with LVH for female participants only. Odds ratios for the subthreshold (mean CES-D ≈ 14) and stable (mean CES-D ≈ 19) groups were 1.49 (95% confidence interval = 1.05-2.13) and 1.88 (95% confidence interval = 1.16-3.04), respectively. For female participants, sex hormone-binding globulin was inversely associated with LVH, and for male participants, bioavailable testosterone was positively associated with concentric geometry.

    CONCLUSIONS: Findings from cross-sectional and longitudinal regression models for female participants, but not male ones, and particularly for Somatic subscale trajectories suggested a plausible link among depression, androgens, and LVH. The role of androgens to the depression-LVH relation requires additional investigation in future studies.

  5. Ning H, Perak AM, Siddique J, Wilkins JT, Lloyd-Jones DM, Allen NB
    PMID: 38639077 DOI: 10.1161/CIRCOUTCOMES.123.010568
    BACKGROUND: 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.

    METHODS: 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.

    RESULTS: 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).

    CONCLUSIONS: These findings support the improved utility of the LE8 algorithm for assessing overall cardiovascular health and future CVD risk.

  6. Wang MC, Freaney PM, Perak AM, Allen NB, Greenland P, Grobman WA, et al.
    Am J Prev Cardiol, 2021 Sep;7:100229.
    PMID: 34401862 DOI: 10.1016/j.ajpc.2021.100229
    Objective: To evaluate contemporary patterns in prepregnancy cardiovascular health (CVH) in the United States (US).

    Methods: We conducted a serial, cross-sectional study of National Center for Health Statistics Natality Data representing all live births in the US from 2011 to 2019. We assigned 1 point for each of four ideal prepregnancy metrics (nonsmoking and ideal body mass index [18.5-24.9 kg/m2] provided by maternal self-report, and absence of hypertension and diabetes ascertained by the healthcare professional at delivery) to construct a prepregnancy clinical CVH score ranging from 0 to 4. We described the distribution of prepregnancy CVH, overall and stratified by self-reported race/ethnicity, age, insurance status, and receipt of the Women, Infants, and Children program (WIC) for supplemental nutrition. We examined trends by calculating average annual percent changes (AAPCs) in optimal prepregnancy CVH (score of 4).

    Results: Of 31,643,982 live births analyzed between 2011 and 2019, 53.6% were to non-Hispanic White, 14.5% non-Hispanic Black, 23.3% Hispanic, and 6.6% non-Hispanic Asian women. The mean age (SD) was 28.5 (5.8) years. The prevalence (per 100 live births) of optimal prepregnancy CVH score of 4 declined from 42.1 to 37.7 from 2011 to 2019, with an AAPC (95% CI) of -1.4% per year (-1.3,-1.5). While the relative decline was observed across all race/ethnicity, insurance, and WIC subgroups, significant disparities persisted by race, insurance status, and receipt of WIC. In 2019, non-Hispanic Black women (28.7 per 100 live births), those on Medicaid (30.4), and those receiving WIC (29.1) had the lowest prevalence of optimal CVH.

    Conclusions: Overall, less than half of pregnant women had optimal prepregnancy CVH, and optimal prepregnancy CVH declined in each race/ethnicity, age, insurance, and WIC subgroup between 2011-2019 in the US. However, there were persistent disparities by race/ethnicity and socioeconomic status.

  7. Cameron NA, Molsberry R, Pierce JB, Perak AM, Grobman WA, Allen NB, et al.
    J Am Coll Cardiol, 2020 Dec 01;76(22):2611-2619.
    PMID: 33183896 DOI: 10.1016/j.jacc.2020.09.601
    BACKGROUND: Rates of maternal mortality are increasing in the United States with significant rural-urban disparities. Pre-pregnancy hypertension is a well-established risk factor for adverse maternal and offspring outcomes.

    OBJECTIVES: The purpose of this study was to describe trends in maternal pre-pregnancy hypertension among women in rural and urban areas in 2007 to 2018 in order to inform community-engaged prevention and policy strategies.

    METHODS: We performed a nationwide, serial cross-sectional study using maternal data from all live births in women age 15 to 44 years between 2007 and 2018 (CDC Natality Database). Rates of pre-pregnancy hypertension were calculated per 1,000 live births overall and by urbanization status. Subgroup analysis in standard 5-year age categories was performed. We quantified average annual percentage change using Joinpoint Regression and rate ratios (95% confidence intervals [CIs]) to compare yearly rates between rural and urban areas.

    RESULTS: Among 47,949,381 live births to women between 2007 and 2018, rates of pre-pregnancy hypertension per 1,000 live births increased among both rural (13.7 to 23.7) and urban women (10.5 to 20.0). Two significant inflection points were identified in 2010 and 2016, with highest annual percentage changes between 2016 and 2018 in rural and urban areas. Although absolute rates were lower in younger compared with older women in both rural and urban areas, all age groups experienced similar increases. The rate ratios of pre-pregnancy hypertension in rural compared with urban women ranged from 1.18 (95% CI: 1.04 to 1.35) for ages 15 to 19 years to 1.51 (95% CI: 1.39 to 1.64) for ages 40 to 44 years in 2018.

    CONCLUSIONS: Maternal burden of pre-pregnancy hypertension has nearly doubled in the past decade and the rural-urban gap has persisted.

  8. Perak AM, Ning H, Kit BK, de Ferranti SD, Van Horn LV, Wilkins JT, et al.
    JAMA, 2019 May 21;321(19):1895-1905.
    PMID: 31112258 DOI: 10.1001/jama.2019.4984
    IMPORTANCE: Favorable trends occurred in the lipid levels of US youths through 2010, but these trends may be altered by ongoing changes in the food supply, obesity prevalence, and other factors.

    OBJECTIVE: To analyze trends in levels of lipids and apolipoprotein B in US youths during 18 years from 1999 through 2016.

    DESIGN, SETTING, AND PARTICIPANTS: Serial cross-sectional analysis of US population-weighted data for youths aged 6 to 19 years from the National Health and Nutrition Examination Surveys for 1999 through 2016. Linear temporal trends were analyzed using multivariable regression models with regression coefficients (β) reported as change per 1 year.

    EXPOSURES: Survey year; examined periods spanned 10 to 18 years based on data availability.

    MAIN OUTCOMES AND MEASURES: Age- and race/ethnicity-adjusted mean levels of high-density lipoprotein (HDL), non-HDL, and total cholesterol. Among fasting adolescents (aged 12-19 years), mean levels of low-density lipoprotein cholesterol, geometric mean levels of triglycerides, and mean levels of apolipoprotein B. Prevalence of ideal and adverse (vs borderline) levels of lipids and apolipoprotein B per pediatric lipid guidelines.

    RESULTS: In total, 26 047 youths were included (weighted mean age, 12.4 years; female, 51%). Among all youths, the adjusted mean total cholesterol level declined from 164 mg/dL (95% CI, 161 to 167 mg/dL) in 1999-2000 to 155 mg/dL (95% CI, 154 to 157 mg/dL) in 2015-2016 (β for linear trend, -0.6 mg/dL [95% CI, -0.7 to -0.4 mg/dL] per year). Adjusted mean HDL cholesterol level increased from 52.5 mg/dL (95% CI, 51.7 to 53.3 mg/dL) in 2007-2008 to 55.0 mg/dL (95% CI, 53.8 to 56.3 mg/dL) in 2015-2016 (β, 0.2 mg/dL [95% CI, 0.1 to 0.4 mg/dL] per year) and non-HDL cholesterol decreased from 108 mg/dL (95% CI, 106 to 110 mg/dL) to 100 mg/dL (95% CI, 99 to 102 mg/dL) during the same years (β, -0.9 mg/dL [95% CI, -1.2 to -0.6 mg/dL] per year). Among fasting adolescents, geometric mean levels of triglycerides declined from 78 mg/dL (95% CI, 74 to 82 mg/dL) in 1999-2000 to 63 mg/dL (95% CI, 58 to 68 mg/dL) in 2013-2014 (log-transformed β, -0.015 [95% CI, -0.020 to -0.010] per year), mean levels of low-density lipoprotein cholesterol declined from 92 mg/dL (95% CI, 89 to 95 mg/dL) to 86 mg/dL (95% CI, 83 to 90 mg/dL) during the same years (β, -0.4 mg/dL [95% CI, -0.7 to -0.2 mg/dL] per year), and mean levels of apolipoprotein B declined from 70 mg/dL (95% CI, 68 to 72 mg/dL) in 2005-2006 to 67 mg/dL (95% CI, 65 to 70 mg/dL) in 2013-2014 (β, -0.4 mg/dL [95% CI, -0.7 to -0.04 mg/dL] per year). Favorable trends were generally also observed in the prevalence of ideal and adverse levels. By the end of the study period, 51.4% (95% CI, 48.5% to 54.2%) of all youths had ideal levels for HDL, non-HDL, and total cholesterol; among adolescents, 46.8% (95% CI, 40.9% to 52.6%) had ideal levels for all lipids and apolipoprotein B, whereas 15.2% (95% CI, 13.1% to 17.3%) of children aged 6 to 11 years and 25.2% (95% CI, 22.2% to 28.2%) of adolescents aged 12 to 19 years had at least 1 adverse level.

    CONCLUSIONS AND RELEVANCE: Between 1999 and 2016, favorable trends were observed in levels of lipids and apolipoprotein B in US youths aged 6 to 19 years.

  9. Perak AM, Khan SS, Colangelo LA, Gidding SS, Armstrong AC, Lewis CE, et al.
    J Am Soc Echocardiogr, 2021 04;34(4):388-400.
    PMID: 33212181 DOI: 10.1016/j.echo.2020.11.002
    BACKGROUND: Little is known about the timing of preclinical heart failure (HF) development, particularly among blacks. The primary aims of this study were to delineate age-related left ventricular (LV) structure and function evolution in a biracial cohort and to test the hypothesis that young-adult LV parameters within normative ranges would be associated with incident stage B-defining LV abnormalities over 25 years, independent of cumulative risk factor burden.

    METHODS: Data from the Coronary Artery Risk Development in Young Adults study were analyzed. Participants (n = 2,833) had a mean baseline age of 30.1 years; 45% were black, and 56% were women. Generalized estimating equation logistic regression was used to estimate age-related probabilities of stage B LV abnormalities (remodeling, hypertrophy, or dysfunction) and logistic regression to examine risk factor-adjusted associations between baseline LV parameters and incident abnormalities. Cox regression was used to assess whether baseline LV parameters associated with incident stage B LV abnormalities were also associated with incident clinical (stage C/D) HF events over >25 years' follow-up.

    RESULTS: Probabilities of stage B LV abnormalities at ages 25 and 60 years were 10.5% (95% CI, 9.4%-11.8%) and 45.0% (95% CI, 42.0%-48.1%), with significant race-sex disparities (e.g., at age 60, black men 52.7% [95% CI, 44.9%-60.3%], black women 59.4% [95% CI, 53.6%-65.0%], white men 39.1% [95% CI, 33.4%-45.0%], and white women 39.1% [95% CI, 33.9%-44.6%]). Over 25 years, baseline LV end-systolic dimension indexed to height was associated with incident systolic dysfunction (adjusted odds ratio per 1 SD higher, 2.56; 95% CI, 1.87-3.52), eccentric hypertrophy (1.34; 95% CI, 1.02-1.75), concentric hypertrophy (0.69; 95% CI, 0.51-0.91), and concentric remodeling (0.68; 95% CI, 0.58-0.79); baseline LV mass indexed to height2.7 was associated with incident eccentric hypertrophy (1.70; 95% CI, 1.25-2.32]), concentric hypertrophy (1.63; 95% CI, 1.19-2.24), and diastolic dysfunction (1.24; 95% CI, 1.01-1.52). Among the entire cohort with baseline echocardiographic data available (n = 4,097; 72 HF events), LV end-systolic dimension indexed to height and LV mass indexed to height2.7 were significantly associated with incident clinical HF (adjusted hazard ratios per 1 SD higher, 1.56 [95% CI, 1.26-1.93] and 1.42 [95% CI, 1.14-1.75], respectively).

    CONCLUSIONS: Stage B LV abnormalities and related racial disparities were present in young adulthood, increased with age, and were associated with baseline variation in indexed LV end-systolic dimension and mass. Baseline indexed LV end-systolic dimension and mass were also associated with incident clinical HF. Efforts to prevent the LV abnormalities underlying clinical HF should start from a young age.

  10. Perak AM, Lancki N, Kuang A, Labarthe DR, Allen NB, Shah SH, et al.
    JAMA, 2021 02 16;325(7):658-668.
    PMID: 33591345 DOI: 10.1001/jama.2021.0247
    Importance: Pregnancy may be a key window to optimize cardiovascular health (CVH) for the mother and influence lifelong CVH for her child.

    Objective: To examine associations between maternal gestational CVH and offspring CVH.

    Design, Setting, and Participants: This cohort study used data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study (examinations: July 2000-April 2006) and HAPO Follow-Up Study (examinations: February 2013-December 2016). The analyses included 2302 mother-child dyads, comprising 48% of HAPO Follow-Up Study participants, in an ancillary CVH study. Participants were from 9 field centers across the United States, Barbados, United Kingdom, China, Thailand, and Canada.

    Exposures: Maternal gestational CVH at a target of 28 weeks' gestation, based on 5 metrics: body mass index, blood pressure, total cholesterol level, glucose level, and smoking. Each metric was categorized as ideal, intermediate, or poor using pregnancy guidelines. Total CVH was categorized as follows: all ideal metrics, 1 or more intermediate (but 0 poor) metrics, 1 poor metric, or 2 or more poor metrics.

    Main Outcomes and Measures: Offspring CVH at ages 10 to 14 years, based on 4 metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Total CVH was categorized as for mothers.

    Results: Among 2302 dyads, the mean (SD) ages were 29.6 (2.7) years for pregnant mothers and 11.3 (1.1) years for children. During pregnancy, the mean (SD) maternal CVH score was 8.6 (1.4) out of 10. Among pregnant mothers, the prevalence of all ideal metrics was 32.8% (95% CI, 30.6%-35.1%), 31.7% (95% CI, 29.4%-34.0%) for 1 or more intermediate metrics, 29.5% (95% CI, 27.2%-31.7%) for 1 poor metric, and 6.0% (95% CI, 3.8%-8.3%) for 2 or more poor metrics. Among children of mothers with all ideal metrics, the prevalence of all ideal metrics was 42.2% (95% CI, 38.4%-46.2%), 36.7% (95% CI, 32.9%-40.7%) for 1 or more intermediate metrics, 18.4% (95% CI, 14.6%-22.4%) for 1 poor metric, and 2.6% (95% CI, 0%-6.6%) for 2 or more poor metrics. Among children of mothers with 2 or more poor metrics, the prevalence of all ideal metrics was 30.7% (95% CI, 22.0%-40.4%), 28.3% (95% CI, 19.7%-38.1%) for 1 or more intermediate metrics, 30.7% (95% CI, 22.0%-40.4%) for 1 poor metric, and 10.2% (95% CI, 1.6%-20.0%) for 2 or more poor metrics. The adjusted relative risks associated with 1 or more intermediate, 1 poor, and 2 or more poor (vs all ideal) metrics, respectively, in mothers during pregnancy were 1.17 (95% CI, 0.96-1.42), 1.66 (95% CI, 1.39-1.99), and 2.02 (95% CI, 1.55-2.64) for offspring to have 1 poor (vs all ideal) metrics, and the relative risks were 2.15 (95% CI, 1.23-3.75), 3.32 (95% CI,1.96-5.62), and 7.82 (95% CI, 4.12-14.85) for offspring to have 2 or more poor (vs all ideal) metrics. Additional adjustment for categorical birth factors (eg, preeclampsia) did not fully explain these significant associations (eg, relative risk for association between 2 or more poor metrics among mothers during pregnancy and 2 or more poor metrics among offspring after adjustment for an extended set of birth factors, 6.23 [95% CI, 3.03-12.82]).

    Conclusions and Relevance: In this multinational cohort, better maternal CVH at 28 weeks' gestation was significantly associated with better offspring CVH at ages 10 to 14 years.

  11. Perak AM, Lancki N, Kuang A, Labarthe DR, Allen NB, Shah SH, et al.
    Am J Obstet Gynecol, 2021 02;224(2):210.e1-210.e17.
    PMID: 32768430 DOI: 10.1016/j.ajog.2020.07.053
    BACKGROUND: The American Heart Association's formal characterization of cardiovascular health combines several metrics in a health-oriented, rather than disease-oriented, framework. Although cardiovascular health assessment during pregnancy has been recommended, its significance for pregnancy outcomes is unknown.

    OBJECTIVE: The purpose of this study was to examine the association of gestational cardiovascular health-formally characterized by a combination of 5 metrics-with adverse maternal and newborn outcomes.

    STUDY DESIGN: We analyzed data from the Hyperglycemia and Adverse Pregnancy Outcome study, including 2304 mother-newborn dyads from 6 countries. Maternal cardiovascular health was defined by the combination of the following 5 metrics measured at a mean of 28 (24-32) weeks' gestation: body mass index, blood pressure, lipids, glucose, and smoking. Levels of each metric were categorized using pregnancy guidelines, and the total cardiovascular health was scored (0-10 points, where 10 was the most favorable). Cord blood was collected at delivery, newborn anthropometrics were measured within 72 hours, and medical records were abstracted for obstetrical outcomes. Modified Poisson and multinomial logistic regression were used to test the associations of gestational cardiovascular health with pregnancy outcomes, adjusted for center and maternal and newborn characteristics.

    RESULTS: The average age of women at study exam was 29.6 years old, and they delivered at a mean gestational age of 39.8 weeks. The mean total gestational cardiovascular health score was 8.6 (of 10); 36.3% had all ideal metrics and 7.5% had 2+ poor metrics. In fully adjusted models, each 1 point higher (more favorable) cardiovascular health score was associated with lower risks for preeclampsia (relative risk, 0.67 [95% confidence interval, 0.61-0.73]), unplanned primary cesarean delivery (0.88 [0.82-0.95]), newborn birthweight >90th percentile (0.81 [0.75-0.87]), sum of skinfolds >90th percentile (0.84 [0.77-0.92]), and insulin sensitivity <10th percentile (0.83 [0.77-0.90]). Cardiovascular health categories demonstrated graded associations with outcomes; for example, relative risks (95% confidence intervals) for preeclampsia were 3.13 (1.39-7.06), 5.34 (2.44-11.70), and 9.30 (3.95-21.86) for women with ≥1 intermediate, 1 poor, or ≥2 poor (vs all ideal) metrics, respectively.

    CONCLUSION: More favorable cardiovascular health at 24 to 32 weeks' gestation was associated with lower risks for several adverse pregnancy outcomes in a multinational cohort.

  12. Lowe LP, Perak AM, Kuang A, Lloyd-Jones DM, Sacks DA, Deerochanawong C, et al.
    Diabetes Res Clin Pract, 2022 Mar;185:109790.
    PMID: 35192911 DOI: 10.1016/j.diabres.2022.109790
    AIMS: To examine associations of pregnancy glycemia with future dyslipidemia.

    METHODS: We analyzed data from Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study participants. We examined associations of gestational diabetes (GDM), sum of fasting, 1-hour, and 2-hour glucose z-scores after 75-g load, insulin sensitivity, and lipid levels at 24-32 weeks' gestation with dyslipidemia 10-14 years postpartum.

    RESULTS: Among 4,693 women, 14.3% had GDM. At follow-up, mean (SD) age was 41.7 (5.7) years, 32.3% had total cholesterol (TC) ≥ 5.17, 27.2% had HDL cholesterol 

  13. Lloyd-Jones DM, Ning H, Labarthe D, Brewer L, Sharma G, Rosamond W, et al.
    Circulation, 2022 Sep 13;146(11):822-835.
    PMID: 35766033 DOI: 10.1161/CIRCULATIONAHA.122.060911
    BACKGROUND: The American Heart Association recently published an updated algorithm for quantifying cardiovascular health (CVH)-the Life's Essential 8 score. We quantified US levels of CVH using the new score.

    METHODS: We included individuals ages 2 through 79 years (not pregnant or institutionalized) who were free of cardiovascular disease from the National Health and Nutrition Examination Surveys in 2013 through 2018. For all participants, we calculated the overall CVH score (range, 0 [lowest] to 100 [highest]), as well as the score for each component of diet, physical activity, nicotine exposure, sleep duration, body mass index, blood lipids, blood glucose, and blood pressure, using published American Heart Association definitions. Sample weights and design were incorporated in calculating prevalence estimates and standard errors using standard survey procedures. CVH scores were assessed across strata of age, sex, race and ethnicity, family income, and depression.

    RESULTS: There were 23 409 participants, representing 201 728 000 adults and 74 435 000 children. The overall mean CVH score was 64.7 (95% CI, 63.9-65.6) among adults using all 8 metrics and 65.5 (95% CI, 64.4-66.6) for the 3 metrics available (diet, physical activity, and body mass index) among children and adolescents ages 2 through 19 years. For adults, there were significant differences in mean overall CVH scores by sex (women, 67.0; men, 62.5), age (range of mean values, 62.2-68.7), and racial and ethnic group (range, 59.7-68.5). Mean scores were lowest for diet, physical activity, and body mass index metrics. There were large differences in mean scores across demographic groups for diet (range, 23.8-47.7), nicotine exposure (range, 63.1-85.0), blood glucose (range, 65.7-88.1), and blood pressure (range, 49.5-84.0). In children, diet scores were low (mean 40.6) and were progressively lower in higher age groups (from 61.1 at ages 2 through 5 to 28.5 at ages 12 through 19); large differences were also noted in mean physical activity (range, 63.1-88.3) and body mass index (range, 74.4-89.4) scores by sociodemographic group.

    CONCLUSIONS: The new Life's Essential 8 score helps identify large group and individual differences in CVH. Overall CVH in the US population remains well below optimal levels and there are both broad and targeted opportunities to monitor, preserve, and improve CVH across the life course in individuals and the population.

  14. Lloyd-Jones DM, Allen NB, Anderson CAM, Black T, Brewer LC, Foraker RE, et al.
    Circulation, 2022 Aug 02;146(5):e18-e43.
    PMID: 35766027 DOI: 10.1161/CIR.0000000000001078
    In 2010, the American Heart Association defined a novel construct of cardiovascular health to promote a paradigm shift from a focus solely on disease treatment to one inclusive of positive health promotion and preservation across the life course in populations and individuals. Extensive subsequent evidence has provided insights into strengths and limitations of the original approach to defining and quantifying cardiovascular health. In response, the American Heart Association convened a writing group to recommend enhancements and updates. The definition and quantification of each of the original metrics (Life's Simple 7) were evaluated for responsiveness to interindividual variation and intraindividual change. New metrics were considered, and the age spectrum was expanded to include the entire life course. The foundational contexts of social determinants of health and psychological health were addressed as crucial factors in optimizing and preserving cardiovascular health. This presidential advisory introduces an enhanced approach to assessing cardiovascular health: Life's Essential 8. The components of Life's Essential 8 include diet (updated), physical activity, nicotine exposure (updated), sleep health (new), body mass index, blood lipids (updated), blood glucose (updated), and blood pressure. Each metric has a new scoring algorithm ranging from 0 to 100 points, allowing generation of a new composite cardiovascular health score (the unweighted average of all components) that also varies from 0 to 100 points. Methods for implementing cardiovascular health assessment and longitudinal monitoring are discussed, as are potential data sources and tools to promote widespread adoption in policy, public health, clinical, institutional, and community settings.
  15. Kim K, Yaffe K, Rehkopf DH, Zheng Y, Nannini DR, Perak AM, et al.
    JAMA Netw Open, 2023 Jun 01;6(6):e2317987.
    PMID: 37306997 DOI: 10.1001/jamanetworkopen.2023.17987
    IMPORTANCE: Adverse childhood experiences (ACEs) are associated with the risk of poorer health, and identifying molecular mechanisms may lay the foundation for health promotion in people with ACEs.

    OBJECTIVE: To investigate the associations of ACEs with changes in epigenetic age acceleration (EAA), a biomarker associated with various health outcomes in middle-aged adults, in a population with balanced race and sex demographics.

    DESIGN, SETTING, AND PARTICIPANTS: Data for this cohort study were from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants in CARDIA underwent 8 follow-up exams from baseline (year 0 [Y0]; 1985-1986) to Y30 (2015-2016), and participant blood DNA methylation information was obtained at Y15 (2000-2001) and Y20 (2005-2006). Individuals from Y15 and Y20 with available DNA methylation data and complete variables for ACEs and covariates were included. Data were analyzed from September 2021 to August 2022.

    EXPOSURES: Participant ACEs (general negligence, emotional negligence, physical violence, physical negligence, household substance abuse, verbal and emotional abuse, and household dysfunction) were obtained at Y15.

    MAIN OUTCOMES AND MEASURES: The primary outcome consisted of results from 5 DNA methylation-based EAA measurements known to be associated with biological aging and long-term health: intrinsic EAA (IEAA), extrinsic EAA (EEAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), and Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE), measured at Y15 and Y20. Linear regression and generalized estimating equations were used to assess associations of the burden of ACEs (≥4 vs <4 ACEs) with EAA adjusting for demographics, health-related behaviors, and early life and adult socioeconomic status.

    RESULTS: A total of 895 participants for Y15 (mean [SD] age, 40.4 [3.5] years; 450 males [50.3%] and 445 females [49.7%]; 319 Black [35.6%] and 576 White [64.4%]) and 867 participants for Y20 (mean [SD] age, 45.4 [3.5] years; 432 males [49.8%] and 435 females [50.2%]; 306 Black [35.3%] and 561 White [64.7%]) were included after excluding participants with missing data. There were 185 participants with (20.7%) vs 710 participants without (79.3%) 4 or more ACEs at Y15 and 179 participants with (20.6%) vs 688 participants without (79.4%) 4 or more ACEs at Y20. Having 4 or more ACEs was positively associated with EAA in years at Y15 (EEAA: β = 0.60 years; 95% CI, 0.18-1.02 years; PhenoAA: β = 0.62 years; 95% CI = 0.13-1.11 years; GrimAA: β = 0.71 years; 95% CI, 0.42-1.00 years; DunedinPACE: β = 0.01; 95% CI, 0.01-0.02) and Y20 (IEAA: β = 0.41 years; 95% CI, 0.05-0.77 years; EEAA: β = 1.05 years; 95% CI, 0.66-1.44 years; PhenoAA: β = 0.57 years; 95% CI, 0.08-1.05 years; GrimAA: β = 0.57 years; 95% CI, 0.28-0.87 years; DunedinPACE: β = 0.01; 95% CI, 0.01-0.02) after adjusting for demographics, health-related behaviors, and socioeconomic status.

    CONCLUSIONS AND RELEVANCE: In this cohort study, ACEs were associated with EAA among middle-aged adults after controlling for demographics, behavior, and socioeconomic status. These findings of the associations between early life experience and the biological aging process in midlife may contribute to health promotion in a life course perspective.

  16. Freaney PM, Harrington K, Molsberry R, Perak AM, Wang MC, Grobman W, et al.
    J Am Heart Assoc, 2022 Jun 07;11(11):e025050.
    PMID: 35583146 DOI: 10.1161/JAHA.121.025050
    Background Adverse pregnancy outcomes (APOs) (hypertensive disorders of pregnancy [HDP], preterm delivery [PTD], or low birth weight [LBW]) are associated adverse maternal and offspring cardiovascular outcomes. Therefore, we sought to describe nationwide temporal trends in the burden of each APO (HDP, PTD, LBW) from 2007 to 2019 to inform strategies to optimize maternal and offspring health outcomes. Methods and Results We performed a serial cross-sectional analysis of APO subtypes (HDP, PTD, LBW) from 2007 to 2019. We included maternal data from all live births that occurred in the United States using the National Center for Health Statistics Natality Files. We quantified age-standardized and age-specific rates of APOs per 1000 live births and their respective mean annual percentage change. All analyses were stratified by self-report of maternal race and ethnicity. Among 51 685 525 live births included, 15% were to non-Hispanic Black individuals, 24% Hispanic individuals, and 6% Asian individuals. Between 2007 and 2019, age standardized HDP rates approximately doubled, from 38.4 (38.2-38.6) to 77.8 (77.5-78.1) per 1000 live births. A significant inflection point was observed in 2014, with an acceleration in the rate of increase of HDP from 2007 to 2014 (+4.1% per year [3.6-4.7]) to 2014 to 2019 (+9.1% per year [8.1-10.1]). Rates of PTD and LBW increased significantly when co-occurring in the same pregnancy with HDP. Absolute rates of APOs were higher in non-Hispanic Black individuals and in older age groups. However, similar relative increases were seen across all age,racial and ethnic groups. Conclusions In aggregate, APOs now complicate nearly 1 in 5 live births. Incidence of HDP has increased significantly between 2007 and 2019 and contributed to the reversal of favorable trends in PTD and LBW. Similar patterns were observed in all age groups, suggesting that increasing maternal age at pregnancy does not account for these trends. Black-White disparities persisted throughout the study period.
  17. Wilkins JT, Ning H, Allen NB, Zheutlin A, Shah NS, Feinstein MJ, et al.
    J Am Coll Cardiol, 2024 Sep 10;84(11):961-973.
    PMID: 39232632 DOI: 10.1016/j.jacc.2024.05.070
    BACKGROUND: The ability of a 1-time measurement of non-high-density lipoprotein cholesterol (non-HDL-C) or low-density lipoprotein cholesterol (LDL-C) to predict the cumulative exposure to these lipids during early adulthood (age 18-40 years) and the associated atherosclerotic cardiovascular disease (ASCVD) risk after age 40 years is not clear.

    OBJECTIVES: The objectives of this study were to evaluate whether a 1-time measurement of non-HDL-C or LDL-C in a young adult can predict cumulative exposure to these lipids during early adulthood, and to quantify the association between cumulative exposure to non-HDL-C or LDL-C during early adulthood and the risk of ASCVD after age 40 years.

    METHODS: We included CARDIA (Coronary Artery Risk Development in Young Adults Study) participants who were free of cardiovascular disease before age 40 years, were not taking lipid-lowering medications, and had ≥3 measurements of LDL-C and non-HDL-C before age 40 years. First, we assessed the ability of a 1-time measurement of LDL-C or non-HDL-C obtained between age 18 and 30 years to predict the quartile of cumulative lipid exposure from ages 18 to 40 years. Second, we assessed the associations between quartiles of cumulative lipid exposure from ages 18 to 40 years with ASCVD events (fatal and nonfatal myocardial infarction and stroke) after age 40 years.

    RESULTS: Of 4,104 CARDIA participants who had multiple lipid measurements before and after age 30 years, 3,995 participants met our inclusion criteria and were in the final analysis set. A 1-time measure of non-HDL-C and LDL-C had excellent discrimination for predicting membership in the top or bottom quartiles of cumulative exposure (AUC: 0.93 for the 4 models). The absolute values of non-HDL-C and LDL-C that predicted membership in the top quartiles with the highest simultaneous sensitivity and specificity (highest Youden's Index) were >135 mg/dL for non-HDL-C and >118 mg/dL for LDL-C; the values that predicted membership in the bottom quartiles were <107 mg/dL for non-HDL-C and <96 mg/dL for LDL-C. Individuals in the top quartile of non-HDL-C and LDL-C exposure had demographic-adjusted HRs of 4.6 (95% CI: 2.84-7.29) and 4.0 (95% CI: 2.50-6.33) for ASCVD events after age 40 years, respectively, when compared with each bottom quartile.

    CONCLUSIONS: Single measures of non-HDL-C and LDL-C obtained between ages 18 and 30 years are highly predictive of cumulative exposure before age 40 years, which in turn strongly predicts later-life ASCVD events.

  18. Pool LR, Petito LC, Yang X, Krefman AE, Perak AM, Davis MM, et al.
    Ann Epidemiol, 2023 Jul;83:40-46.e4.
    PMID: 37084989 DOI: 10.1016/j.annepidem.2023.04.007
    PURPOSE: Many children have non-ideal cardiovascular health (CVH), but little is known about the course of CVH in early childhood. We identified CVH trajectories in children and assess the generalizability of these trajectories in an external sample.

    METHODS: We used data spanning 2010-2018 from children aged 2-12 years within the Chicago Area Patient-Centered Outcomes Research Network-an electronic health record network. Four clinical systems comprised the derivation sample and a fifth the validation sample. Body mass index, blood pressure, cholesterol, and blood glucose were categorized as ideal, intermediate, and poor using clinical measurements, laboratory readings, and International Classification of Diseases diagnosis codes and summed for an overall CVH score. Group-based trajectory modeling was used to create CVH score trajectories which were assessed for classification accuracy in the validation sample.

    RESULTS: Using data from 122,363 children (47% female, 47% non-Hispanic White) three trajectories were identified: 59.5% maintained high levels of clinical CVH, 23.4% had high levels of CVH that declined, and 17.1% had intermediate levels of CVH that further declined with age. A similar classification emerged when the trajectories were fitted in the validation sample.

    CONCLUSIONS: Stratification of CVH was present by age 2, implicating the need for early life and preconception prevention strategies.

  19. Cameron NA, Freaney PM, Wang MC, Perak AM, Dolan BM, O'Brien MJ, et al.
    Circulation, 2022 Feb 15;145(7):549-551.
    PMID: 35157521 DOI: 10.1161/CIRCULATIONAHA.121.057107
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