PDAY risk score predicts cardiovascular events in young adults: the CARDIA study.

AIMS: Atherosclerotic cardiovascular disease (ASCVD) risk prediction equations apply to older adults. For this study, the Pathobiologic Determinants of Atherosclerosis in Youth (PDAY) risk score, based on post-mortem measurements of atherosclerosis in 15-34-year olds dying accidentally, was used to predict ASCVD events, specifically myocardial infarction and revascularization, in middle age, from risk measured at ≤40 years of age. METHODS AND RESULTS: The Coronary Artery Risk Development in Young Adults Study (CARDIA) collected longitudinal cardiovascular risk data, coronary artery calcium (CAC) scores, and ASCVD data beginning at age 18 and 30 years with 30-year follow-up. Predictive accuracy for ASCVD of the PDAY risk score, calculated at baseline (mean age 24) and at all six CARDIA examinations up until year 15, was examined. We also examined whether the presence of CAC improved model discrimination. The cohort for this study comprised 5004 Black and White men and women, at baseline and 3558 with data at year 15. Each standard deviation increase in PDAY score, at each examination, was significantly associated with future ASCVD. Hazard ratios (per standard deviation) increased from 1.74 to 2.04 from year 0 to year 15. C-statistics ranged from 0.771 to 0.794. Coronary artery calcium measurement at age 33-45 years improved risk prediction only if the score was 0. Cumulative risk exposure over the first 15 years of the CARDIA study also had high-predictive value (c-statistic 0.798, 95% confidence interval 0.762-0.835). CONCLUSION: The PDAY risk score may be used in young adults, prior to age 40 years to predict ASCVD events.

The influence of individual and neighborhood-level characteristics on rural-urban disparities in cardiovascular disease mortality among U.S. women diagnosed with breast and gynecologic cancers.

OBJECTIVE: Rural-urban disparities exist in cancer and cardiovascular disease (CVD) mortality. Investigations of CVD mortality among breast and gynecologic cancer (BGC) survivors from rural/urban communities are limited. We evaluated the influence of individual and neighborhood-level factors on rural-urban disparities in CVD mortality among BGC survivors. METHODS: Data were from 1,139,767 women aged ≥20 years from the Surveillance, Epidemiology, and End Results program who were diagnosed with BGC from 2000 to 2016 that was merged with Area Health Resource Files for neighborhood-level factors (smoking, cancer screening, primary care provider density and socioeconomic index). Standardized mortality ratios (SMRs) for CVD mortality were calculated and multilevel Cox models, accounting for competing events, were used to estimate hazards ratios (HR) and 95% confidence intervals (CI). RESULTS: The average age of BGC survivors was 60 years, with 10.3% of them living in rural counties. During a median follow-up of 5.1 years, 47,995 CVD deaths occured. Women with BGC had excess CVD mortality compared to general population women (SMR 6.05; CI: 6.00-6.11). This risk was highest among women aged <50 years (SMR = 27.16; CI: 25.74-28.62). In models adjusted for demographics, cancer stage and cancer therapy, women with BGC in rural communities had higher CVD deaths than those in urban communities (HR = 1.10, CI:1. 05-1.15). Additional adjustment for neighborhood-level characteristics attenuated the relation of rurality with CVD mortality (HR = 1.02, CI: 0.98-1.07). CONCLUSIONS: BGC survivors living in rural communities have elevated risk of CVD mortality. Neighborhood-level characteristics explained the rural-urban disparities in CVD mortality observed among BGC survivors.

The Joint Association of Septicemia and Cerebrovascular Diseases with In-Hospital MortalityAmong Patients with Left Ventricular Assist Device in the United States.

OBJECTIVES: Left ventricular assist device (LVAD) is associated with complications such as cerebrovascular diseases (CEVD) as well as septicemia which is often preventable. With their use increasing in the U.S., identifying patients with LVAD who are at high risk for short-term mortality is essential for targeted effective patient management strategies to prevent adverse outcomes. We investigated the individual and joint association of CEVD and septicemia with the risk of in-hospital mortality in patients with LVAD in the U.S. MATERIALS AND METHODS: We used data from the National Inpatient Sample from 2004 to 2015 to identify patients ≥18 years of age who underwent LVAD implantation by means of International Classification of Disease, 9th Revision, codes. Multivariable hierarchical negative binomial regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) for in-hospital mortality by CEVD-septicemia status. RESULTS: The mean age of the 4638 patients was 56 years, and 23% of them were women. Approximately 13% of patients had septicemia; 7% had CEVD and 2% had both conditions. In models adjusted for demographic, lifestyle/behavior factors and comorbid conditions, the risk of in-hospital mortality was almost threefold higher among patients with septicemia alone (RR=2.84, CI:2.24-3.60); two-and-half fold higher among patients with CEVD alone (RR=2.53, CI:1.85-3.48); and almost fourfold among patients with both septicemia and CEVD (RR=3.76, CI: 2.38-5.94, Pinteraction = <0.001) CONCLUSION: The presence of both septicemia and CEVD was associated with a substantially higher risk of in-hospital mortality among LVAD patients when compared to septicemia or CEVD alone.

Pathophysiology of Hypertensive Heart Disease: Beyond Left Ventricular Hypertrophy.

PURPOSE OF REVIEW: Given that the life expectancy and the burden of hypertension are projected to increase over the next decade, hypertensive heart disease (HHD) may be expected to play an even more central role in the pathophysiology of cardiovascular disease (CVD). A broader understanding of the features and underlying mechanisms that constitute HHD therefore is of paramount importance. RECENT FINDINGS: HHD is a condition that arises as a result of elevated blood pressure and constitutes a key underlying mechanism for cardiovascular morbidity and mortality. Historically, studies investigating HHD have primarily focused on left ventricular (LV) hypertrophy (LVH), but it is increasingly apparent that HHD encompasses a range of target-organ damage beyond LVH, including other cardiovascular structural and functional adaptations that may occur separately or concomitantly. HHD is characterized by micro- and macroscopic myocardial alterations, structural phenotypic adaptations, and functional changes that include cardiac fibrosis, and the remodeling of the atria and ventricles and the arterial system. In this review, we summarize the structural and functional alterations in the cardiac and vascular system that constitute HHD and underscore their underlying pathophysiology.

Longitudinal Qualitative and Quantitative Evaluation of SARS-CoV-2 Antibodies in Immunized Health Care Workers.

CONTEXT.­: Many studies have depended on qualitative antibody assays to investigate questions related to COVID-19 infection, vaccination, and treatment. OBJECTIVE.­: To evaluate immunoglobulin G (IgG) levels in vaccinated individuals over time and characterize limitations of qualitative and quantitative antibody assays. DESIGN.­: Longitudinal serum samples (n = 339) were collected from 72 health care workers vaccinated against COVID-19. SARS-CoV-2 IgG levels before, during, and after vaccination were measured by using a qualitative anti-spike protein IgG assay and a quantitative anti-S1 IgG assay. Assay results were compared to understand antibody dynamics related to vaccination. RESULTS.­: Qualitative testing demonstrated 100% seroconversion after the first vaccine dose, peak IgG levels after the second vaccine dose, and a progressive 50% decline during the next 8 months. Quantitative testing demonstrated that IgG levels during and after vaccination were above the analytical measurement range. CONCLUSIONS.­: Qualitative testing demonstrates expected changes in SARS-CoV-2 IgG levels related to sequential vaccine doses and time since antigen exposure. However, proportional changes in the associated numerical signals are very likely inaccurate. Adoption of standardized quantitative SARS-CoV-2 antibody testing with a broad analytical measurement range is essential to determine a correlate of protection from COVID-19 that can be scaled for widespread use.

Reduced Risk of All-Cause, Cancer-, and Cardiovascular Disease-Related Mortality among Patients with Primary Malignant Cardiac Tumors Receiving Chemotherapy in the United States.

Primary malignant cardiac tumors (PMCTs) are rare but lethal neoplasms. There are limited evidence-based treatment guidelines for PMCTs. We evaluated the relation of chemotherapy with mortality outcomes in patients with PMCTs in the United States. Data were from patients aged ≥ 20 years from the Surveillance, Epidemiology, and End Results program who were diagnosed with PMCTs from 2000 to 2020. Cox regression, competing risk, and propensity score analyses were performed to estimate hazard ratios (HR) and confidence intervals (CI). About 53% of the 563 patients with PMCTs received chemotherapy as the first course of treatment. During a mean follow-up of 24.7 months (median: 10), 458 deaths occurred with 81.7% and 9.4% due to cancer and cardiovascular disease (CVD), respectively. In models adjusted for sociodemographic and clinico-pathophysiological factors including histology, receipt of chemotherapy was associated with low risk for all-cause (HR: 0.56, 95%CI: 0.45-0.69), cancer (HR: 0.63, 95%CI: 0.50-0.80) and CVD mortality (HR: 0.27, 95%CI: 0.12-0.58). Patients who had both chemotherapy and surgery had the lowest risk for all-cause and cancer mortality. This study suggests that the subpopulations of patients with PMCTs who receive chemotherapy may have better prognosis than those who do not receive this therapy regardless of histology.

Perceived neighborhood social cohesion and the 10-year risk of cardiovascular disease in low- and middle-income countries: The World Health Organization Study on Global Aging and Adult Health.

Low- and middle-income countries (LMICs) bear the greatest burden of cardiovascular disease (CVD) worldwide. Emerging evidence, mostly from industrialized countries, suggest that neighborhood characteristics influence cardiovascular health. This study presents results from 27,797 participants living in six LMICs on the association of perceived neighborhood social cohesion, the degree of connectedness among neighbors, with 10-year risk of CVD. We observed that greater perceived neighborhood social cohesion was associated with lower odds of high (>20%) 10-year CVD risk (OR = 0.67, 95%CI: 0.53-0.86). These novel findings, suggest that interventions to enhance social cohesion may have beneficial effects on cardiovascular health in LMICs.

The Association of Mental Health Disorders with Takotsubo Syndrome (Broken Heart Syndrome) Among Older Women.

Background: The prevalence of mental health disorders (MHD) and takotsubo syndrome (TS), also known as broken heart syndrome, is increasing and more common in older women. Mortality among persons with TS is comparable to that of persons with myocardial infarction. Although TS is poorly understood, it is thought to be precipitated by psychological stress. We examined the relationship between MHD and TS among elderly American women. Materials and Methods: Data consisted of 10.9 million hospitalizations among women aged ≥60 years recorded in the National Inpatient Sample from 2007 to 2015. International Classification of Diseases, Ninth Revision, codes were used to define TS, MHD, and other chronic conditions. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between MHD and TS. Results: The mean age of patients was 76 years, with 38% of them diagnosed with MHD. Over the 9-year period, the prevalence of TS hospitalizations increased by almost fourfold from 37.1/100,000 to 154.7/100,000, with a higher prevalence among patients with MHD. In multivariable adjusted models, MHD was associated with elevated odds of TS (OR = 1.25; 95% CI: 1.18-1.32), with the odds increasing with the frequency of MHD diagnosis. Among patients with one MHD, the odds of TS were significantly higher among those diagnosed with adjustment, anxiety, and mood disorders but lower among those with suicide ideations and personality disorders. Conclusions: The presence of MHD was associated with elevated odds of TS. Understanding underlying mechanisms linking MHD with TS will enhance MHD management.

Low endogenous estradiol levels are associated with elevated risk of cardiovascular disease mortality in young and middle-aged men in the United States.

BACKGROUND AND AIMS: Evidence for the association of total estradiol (E2) with cardiovascular disease (CVD) in young men is limited. We investigated the association of total E2 or free estradiol (FE2) and CVD mortality in a nationally representative multiracial sample of young and middle-aged men in the United States. METHODS: Data were from 954 men without CVD, cancer, diabetes and not on androgen therapy or taking anabolic steroids, who participated in the National Health and Nutrition Examination Survey (1988-1991), for whom E2 was measured, and were followed for mortality through to 2015. Fasting serum levels of E2 were measured using competitive electrochemiluminescence immunoassays. Free estradiol was estimated from the levels of estradiol, sex hormone binding globulin, and albumin. International Classification of Diseases codes were used to define CVD mortality. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The average age of participants at baseline was 35.7 ± 11.6 years, with 11% and 6% reporting Black and Hispanic race and ethnicity, respectively. During a median follow-up of 25.2 years, 40 CVD deaths were recorded. Controlling for baseline demographic and CVD risk factors, and total testosterone levels, a 1 standard deviation decrement in log E2 (HR: 2.33, 95%CI: 1.11-5.00) or FE2 (HR: 1.89, 95%CI: 1.01-3.57) was associated with elevated risk of CVD mortality. This elevated risk was largely limited to non-Hispanic White men. CONCLUSIONS: In this study, low levels of E2 or FE2 were associated with elevated risk of CVD mortality.

The association of age at natural menopause with pre- to postmenopausal changes in left ventricular structure and function: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

OBJECTIVE: The association between menopause and incident cardiovascular disease (CVD) is controversial. We evaluated the relationships of estrogen deficiency (ovarian reproductive aging) assessed by age at natural menopause (ANM), chronological aging, and antecedent CVD risk factors (biological aging) with left ventricular (LV) structure and function among women transitioning from pre- to postmenopause. METHODS: We studied 771 premenopausal women (37% Black) from the Coronary Artery Risk Development in Young Adults Study with echocardiographic data in 1990 to 1991 (mean age: 32 y) who later reached natural menopause by 2015 to 2016 and had repeated echocardiographic measurements. Linear regression models were used to evaluate the association of ANM with parameters of LV structure and function. RESULTS: Mean ANM was 50 (± 3.8) years and the average time from ANM to the last echocardiograph was 7 years. In cross-sectional analyses, a 1-year increase in ANM was significantly associated with lower postmenopausal LV mass (LVM), LVM indexed to body surface area, LV mass-to-volume ratio, and relative wall thickness. In age-adjusted longitudinal analyses, higher ANM was inversely associated with pre- to postmenopausal changes in LVM (ß = -0.97; 95% CI: -1.81 to -0.13, P = 0.024) and LVM indexed (ß = -0.48; 95% CI: -0.89 to -0.07, P = 0.021). Controlling for baseline LV structure parameters and traditional CVD risk factors attenuated these associations. Further adjustment for hormone therapy uses did not alter these results. CONCLUSION: In this study, premenopausal CVD risk factors attenuated the association of ANM with changes in LV structure parameters. These data suggest that premenopausal CVD risk factors may predispose women to elevated future CVD risk more than ovarian aging.

Cardiac microstructural alterations measured by echocardiography identify sex-specific risk for heart failure.

OBJECTIVE: Established preclinical imaging assessments of heart failure (HF) risk are based on macrostructural cardiac remodelling. Given that microstructural alterations may also influence HF risk, particularly in women, we examined associations between microstructural alterations and incident HF. METHODS: We studied N=2511 adult participants (mean age 65.7±8.8 years, 56% women) of the Framingham Offspring Study who were free of cardiovascular disease at baseline. We employed texture analysis of echocardiography to quantify microstructural alteration, based on the high spectrum signal intensity coefficient (HS-SIC). We examined its relations to incident HF in sex-pooled and sex-specific Cox models accounting for traditional HF risk factors and macrostructural alterations. RESULTS: We observed 94 new HF events over 7.4±1.7 years. Individuals with higher HS-SIC had increased risk for incident HF (HR 1.67 per 1-SD in HS-SIC, 95% CI 1.31 to 2.13; p<0.0001). Adjusting for age and antihypertensive medication use, this association was significant in women (p=0.02) but not men (p=0.78). Adjusting for traditional risk factors (including body mass index, total/high-density lipoprotein cholesterol, blood pressure traits, diabetes and smoking) attenuated the association in women (HR 1.30, p=0.07), with mediation of HF risk by the HS-SIC seen for a majority of these risk factors. However, the HS-SIC association with HF in women remained significant after adjusting for relative wall thickness (representing macrostructure alteration) in addition to these risk factors (HR 1.47, p=0.02). CONCLUSIONS: Cardiac microstructural alterations are associated with elevated risk for HF, particularly in women. Microstructural alteration may identify sex-specific pathways by which individuals progress from risk factors to clinical HF.

Association of marital status with takotsubo syndrome (broken heart syndrome) among adults in the United States.

BACKGROUND: The pathophysiology of takotsubo syndrome (TTS) is not well understood, however, it is often precipitated by psychological or physical stress. Marital status is related to emotional stress, but its associations with TTS are limited. AIM: To explored the potential association between marital status and TTS. METHODS: We conducted a case-control study using data on patients aged ≥ 40 years with marital status data in the National Hospital Discharge Survey (2006-2010). The International Classification of Diseases Ninth Revision codes were used to identify cases with TTS and other comorbid conditions. Each case was matched to 5 controls by age, sex, year of TTS diagnosis and bed size of hospital. Two sets of controls were selected: Acute myocardial infarction (AMI) controls and non-cardiovascular disease (CVD) controls. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of marital status with TTS. RESULTS: The 59 patients with TTS who had information on marital status were matched to 295 controls with AMI and 295 non-CVD controls, resulting in a sample of 649 patients. The average age of cases was 69.7 ± 11 years with 90% being women and 88% reporting White race. In multivariable-adjusted models, compared to singles, patients who were married had lower odds of TTS (OR = 0.86, 95%CI: 0.79-0.93) while those who were widowed (OR = 1.14, 95%CI: 1.05-1.23) or divorced/separated (OR = 1.32, 95%CI: 1.21-1.45) had elevated odds for TTS when compared to non-CVD controls. Similar results were observed when cases were compared to controls with AMI. CONCLUSION: In this study, being married was associated with lower odds for TTS while being divorced/separated or widowed was related to elevated odds for TTS. These novel findings that underscore the potential importance of social factors like marital status in the development of TTS need confirmation in larger studies.

Associations between menopause, cardiac remodeling, and diastolic function: the CARDIA study.

OBJECTIVES: Heart failure with preserved ejection fraction (HFpEF) affects more women than men. Menopause may influence HFpEF development in women. We assessed cross-sectional and longitudinal associations between menopause and echocardiographic measures of left ventricular (LV) function and cardiac remodeling. METHODS: We studied 1,723 women with available echo data from at least two of: year 5 (Y5) (1990-1991), Y25 (2010-2011), or Y30 (2015-2016) in the Coronary Artery Risk Development in Young Adults study. Cardiac structure and function were measured using 2D and Doppler echocardiography. Cross-sectional associations between menopausal status and repeated echo measures at Y25 and Y30 were analyzed using linear mixed models. Two-segmented models were used to compare longitudinal changes in echocardiographic measures in the premenopausal period to changes in the postmenopausal period. RESULTS: Mean ±â€ŠSD age (years) at enrollment was 27 ±â€Š3 in those with menopause by Y25, 25 ±â€Š3 in those with menopause between Y25 and Y30, and 21 ±â€Š3 in those premenopausal at Y30. There were no significant differences in race, body mass index, systolic blood pressure, or diabetes between the groups. Postmenopausal women had higher early diastolic mitral inflow (E) to annular (e') velocity ratio than premenopausal after adjusting for demographics and risk factors (P < 0.05). Menopause was associated with relative increases in the rates of change in LV mass and left atrial volume, even after adjustment. Change in E/e' ratio was similar before and after menopause. CONCLUSIONS: Menopause is associated cross-sectionally with worse diastolic function and longitudinally with adverse LV and left atrial remodeling. This may contribute to the increased HFpEF risk in postmenopausal women.

Video Summary:http://links.lww.com/MENO/A787 .

Long-term cumulative blood pressure in young adults and incident heart failure, coronary heart disease, stroke, and cardiovascular disease: The CARDIA study.

AIMS: Cumulative blood pressure (BP) is a measure that incorporates the severity and duration of BP exposure. The prognostic significance of cumulative BP in young adults for cardiovascular diseases (CVDs) in comparison to BP severity alone is, however, unclear. METHODS AND RESULTS: We investigated 3667 Coronary Artery Risk Development in Young Adults participants who attended six visits over 15 years (year-0 (1985-1986), year-2, year-5, year-7, year-l0, and year-15 exams). Cumulative BP was calculated as the area under the curve (mmHg × years) from year 0 through year 15. Cox models assessed the association between cumulative BP (year 0 through year 15), current BP (year 15), and BP change (year 0 and year 15) and CVD outcomes. Mean (standard deviation) age at year 15 was 40.2 (3.6) years, 44.1% were men, and 44.1% were African-American. Over a median follow-up of 16 years, there were 47 heart failure (HF), 103 coronary heart disease (CHD), 71 stroke, and 191 CVD events. Cumulative systolic BP (SBP) was associated with HF (hazard ratio (HR) = 2.14 (1.58-2.90)), CHD (HR = 1.49 (1.19-1.87)), stroke (HR = 1.81 (1.38-2.37)), and CVD (HR = 1.73 (1.47-2.05)). For CVD, the C-statistic for SBP (year 15) was 0.69 (0.65-0.73) and change in C-statistic with the inclusion of SBP change and cumulative SBP was 0.60 (0.56-0.65) and 0.72 (0.69-0.76), respectively. For CVD, using year-15 SBP as a reference, the net reclassification index (NRI) for cumulative SBP was 0.40 (p < 0.0001) and the NRI for SBP change was 0.22 (p = 0.001). CONCLUSIONS: Cumulative BP in young adults was associated with the subsequent risk of HF, CHD, stroke, and CVD. Cumulative BP provided incremental prognostic value and improved risk reclassification for CVD, when compared to single BP assessments or changes in BP.

Family history of premature myocardial infarction modifies the associations between bilateral oophorectomy and cardiovascular disease mortality in a US national cohort of postmenopausal women.

OBJECTIVE: To test the hypothesis that a family history of premature myocardial infarction (FHPMI) will modify the associations between bilateral salpingo-oophorectomy (BSO) and mortality due to heart disease (HD), cardiovascular disease (CVD), or all-cause mortality with stronger associations observed for BSO occurring before 45 years. METHODS: We analyzed data from 2,763 postmenopausal women aged 40 years or older who participated in the National Health and Nutrition Examination Survey (1988-1994) and were followed through December 31, 2015. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality outcomes (HD, CVD, and all-cause). RESULTS: At baseline, the average age was 62 years. There were 610 women with BSO, 338 women with FHPMI, and 95 women with both BSO and FHPMI. During a median follow-up of 22 years, 1,713 deaths occurred of which 395 and 542 were attributed to HD and CVD, respectively. In models adjusting for CVD risk factors and hormone therapy use, HD mortality was greater among women with both BSO and FHPMI compared to those without either of these conditions (HR: 2.88, 95% CI: 1.72-4.82, PInteraction = 0.016). HD mortality was higher among women with FHPMI and BSO at an earlier age (<45 y: HR: 4.32, 95% CI: 1.95-9.50 vs ≥45 y: HR: 1.60, 95% CI: 0.63-4.09). Similar observations were seen for CVD and all-cause mortality. CONCLUSIONS: In this study, the risk of HD, CVD, and all-cause mortality in women with BSO was modified by an FHPMI with the risk limited to women undergoing BSO at younger ages.

Association Between Visit-to-Visit Blood Pressure Variability in Early Adulthood and Myocardial Structure and Function in Later Life.

Importance: Long-term blood pressure (BP) variability has emerged as a reproducible measure that is associated with heart failure independent of systemic BP. Visit-to-visit BP variability may be associated with the risk of heart failure early in the life course and thus may be reflected in subclinical alterations in cardiac structure and function. Objective: To evaluate the association between visit-to-visit BP variability in early adulthood and myocardial structure and function in middle age. Design, Setting, and Participants: This cohort study used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a community-based cohort study of 5115 participants aged 18 to 30 years at baseline (year 0; March 25, 1985, to June 7, 1986) and followed up over a 30-year interval. A total of 2400 CARDIA study participants underwent evaluation at 4 field sites (Birmingham, Alabama; Oakland, California; Chicago, Illinois; and Minneapolis, Minnesota). Blood pressure was measured at 8 visits over a 25-year interval and participants received echocardiograms at year 25 (June 1, 2010, to August 31, 2011). Data analysis was conducted from June 7, 1986, to August 31, 2011. Exposures: Visit-to-visit systolic and diastolic BP variability measures included SD, average real variability, and variability independent of the mean. Main Outcomes and Measures: Echocardiographic indices of myocardial structure, systolic function, and diastolic function at the year 25 examination. Results: Of the 2400 participants, 1024 were men (42.7%) and 976 were African American (40.7%); mean (SD) age at the year 25 examination was 50.4 (3.6) years. Per 1-SD increment, greater visit-to-visit systolic BP variability independent of the mean was associated with higher left-ventricular (LV) mass index (ß [SE], 2.66 [0.4] g/m2, P < .001), worse diastolic function (early peak diastolic mitral annular velocity [é]) (ß [SE], -0.40 [0.1] cm/s, P < .001), higher LV filling pressures (mitral inflow velocity to early diastolic mitral annular velocity [E/é]) ß [SE], 0.37 [0.1] cm/s, P < .001), and worse global longitudinal strain (ß [SE], 0.17 [0.1], P = .002). Similarly, greater visit-to-visit diastolic BP variability was associated with higher LV mass index (ß [SE], 3.21 [0.5] g/m2, P < .001), worse diastolic function (é: ß [SE], -0.24 [0.1] cm/s [P < .001]; E/é: ß [SE], 0.23 [0.1] cm/s [P < .001]), and worse global longitudinal strain (ß [SE], 0.13 [0.1], P = .02). The findings remained consistent when other BP variability measures were used (SD and average real variability). Conclusions and Relevance: In this cohort study using data from the CARDIA study, greater visit-to-visit systolic and diastolic BP variability have been associated with adverse alterations in cardiac structure as well as systolic and diastolic function independent of mean BP levels.

Long-Term Blood Pressure Variability in Young Adulthood and Coronary Artery Calcium and Carotid Intima-Media Thickness in Midlife: The CARDIA Study.

Recent evidence links long-term (visit-to-visit) blood pressure (BP) variability to the risk of cardiovascular disease, independent of mean BP levels. Potential associations between long-term BP variability and cardiovascular disease risk may be reflected in early life course alterations in coronary artery calcium (CAC) and carotid intima-media thickness. We evaluated 2482 CARDIA study (Coronary Artery Risk Development in Young Adults) participants (mean [SD] age at the year 20 exam [2005-2006] was 45.4 [3.6] years, 43.2% men, and 41.3% black). We included participants with BP assessments across 20-years (year 0, 2, 5, 7, 10, 15, 20 exams) and carotid intima-media thickness and CAC data at the year 20 exam. BP variability was assessed using variability independent of the mean and SD. Adjusted multivariable linear or logistic regression models (as appropriate) were used to assess associations between long-term BP variability measures and carotid intima-media thickness. and CAC (ln [CAC+1] and prevalent CAC). Long-term systolic BP variability independent of the mean (per 1 SD) was positively associated with carotid intima-media thickness (ß=10 µm, SE=3, P=0.002). Similarly, long-term diastolic BP variability independent of the mean was associated with carotid intima-media thickness (ß=10 µm, SE (3), P=0.001). Long-term BP variability was not associated with either ln [CAC+1] or prevalent CAC. Long-term systolic and diastolic BP variability across early adulthood was positively associated with modest adverse midlife alterations in carotid intima-media thickness but not to CAC. Our findings provide further insights into pathophysiologic mechanisms that link long-term BP variability to cardiovascular disease.

Coffee and tea consumption in the early adult lifespan and left ventricular function in middle age: the CARDIA study.

AIMS: The long-term impact of coffee or tea consumption on subclinical left ventricular (LV) systolic or diastolic function has not been previously studied. We examined the association between coffee or tea consumption beginning in early adulthood and cardiac function in midlife. METHODS AND RESULTS: We investigated 2735 Coronary Artery Risk Development in Young Adults (CARDIA) study participants with long-term total caffeine intake, coffee, and tea consumption data from three visits over a 20 year interval and available echocardiography indices at the CARDIA Year-25 exam (2010-2011). Linear regression models were used to assess the association between caffeine intake, tea, and coffee consumption (independent variables) and echocardiography outcomes [LV mass, left atrial volume, and global longitudinal strain (GLS), LV ejection fraction (LVEF), and transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e´)]. Models were adjusted for standard cardiovascular risk factors, socioeconomic status, physical activity, alcohol use, and dietary factors (calorie intake, whole and refined grain intake, and fruit and vegetable consumption). Mean (standard deviation) age was 25.2 (3.5) years at the CARDIA Year-0 exam (1985-1986), 57.4% were women, and 41.9% were African-American. In adjusted multivariable linear regression models assessing the relationship between coffee consumption and GLS, beta coefficients when comparing coffee drinkers of <1, 1-2, 3-4, and >4 cups/day with non-coffee drinkers were ß = -0.30%, P < 0.05; ß = -0.35%, P < 0.05; ß = -0.32%, P < 0.05; ß = -0.40%, P > 0.05; respectively (more negative values implies better systolic function). In adjusted multivariable linear regression models assessing the relationship between coffee consumption and E/e´, beta coefficients when comparing coffee drinkers of <1, 1-2, 3-4, and >4 cups/day with non-coffee drinkers were ß = -0.29, P < 0.05; ß = -0.38, P < 0.01; ß = -0.20, P > .05; and ß = -0.37, P > 0.05, respectively (more negative values implies better diastolic function). High daily coffee consumption (>4 cups/day) was associated with worse LVEF (ß = -1.69, P < 0.05). There were no associations between either tea drinking or total caffeine intake and cardiac function (P > 0.05 for all). CONCLUSIONS: Low-to-moderate daily coffee consumption from early adulthood to middle age was associated with better LV systolic and diastolic function in midlife. High daily coffee consumption (>4cups/day) was associated with worse LV function. There was no association between caffeine or tea intake and cardiac function.