Financial strain is associated with poorer cardiovascular health: The multi-ethnic study of atherosclerosis.

Objective: Psychosocial stress is associated with increased cardiovascular disease (CVD) risk. The relationship between financial strain, a toxic form of psychosocial stress, and ideal cardiovascular health (CVH) is not well established. We examined whether financial strain was associated with poorer CVH in a multi-ethnic cohort free of CVD at baseline. Methods: This was a cross-sectional analysis of 6,453 adults aged 45-84 years from the Multi-Ethnic Study of Atherosclerosis. Financial strain was assessed by questionnaire and responses were categorized as yes or no. CVH was measured from 7 metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood glucose and blood pressure). A CVH score of 14 was calculated by assigning points to the categories of each metric (poor = 0 points, intermediate = 1 point, ideal = 2 points). Multinomial logistic regression was used to examine the association of financial strain with the CVH score (inadequate 0-8, average 9-10, and optimal 11-14 points) adjusting for sociodemographic factors, depression and anxiety. Results: The mean age (SD) was 62 (10) and 53 % were women. Financial strain was reported by 25 % of participants. Participants who reported financial strain had lower odds of average (OR, 0.82 [95 % CI, 0.71, 0.94]) and optimal (0.73 [0.62, 0.87]) CVH scores. However, in the fully adjusted model, the association was only significant for optimal CVH scores (0.81, [0.68, 0.97]). Conclusion: Financial strain was associated with poorer CVH. More research is needed to understand this relationship so the burden of CVD can be decreased, particularly among people experiencing financial hardship.

Female-specific risk factors of parity and menopause age and risk of carotid plaque: the multi-ethnic study of atherosclerosis.

BACKGROUND: Female-specific factors of grand multiparity (≥5 births) and early menopause age are associated with an increased risk of cardiovascular disease (CVD). However, mechanisms are incompletely understood. Carotid plaque is a marker of subclinical atherosclerosis and associated with increased CVD risk. We evaluated the association of female-specific factors with plaque burden. METHODS: We included 2,313 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis, free of clinical CVD, whose parity and menopause age were ascertained by questionnaires and carotid plaque measured by ultrasound at baseline and 10 years later. Parity was categorized as nulliparity (reference), 1-2, 3-4 and ≥5 live births. Menopause age was categorized as <45, 45-49, 50-54 (reference) and ≥55 years. Multivariable regression was performed to evaluate the association of parity and menopause age with carotid plaque presence (yes/no) and extent [carotid plaque score (CPS)]. RESULTS: The mean age was 64±9 years; 52.3% had prevalent carotid plaque at baseline. Compared to nulliparity, grand multiparity was significantly associated with prevalent carotid plaque after adjustment for CVD risk factors (prevalence ratio 1.17 (95% CI 1.03-1.35)) and progression of CPS over 10 years [percent difference 13% (95% CI 3-23)]. There was not any significant association of menopause age with carotid plaque presence or progression in fully-adjusted models. CONCLUSION: In a multiethnic cohort, grand multiparity was independently associated with carotid plaque presence and progression. Early menopause, a known risk factor for CVD, was not captured by carotid plaque in this study. These findings may have implications for refining CVD risk assessment in women.

Hepatocyte Growth Factor and 10-Year Change in Left Ventricular Structure: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background: Hepatocyte growth factor (HGF) is a cytokine linked to incident heart failure (HF), particularly HF with preserved ejection fraction (HFpEF). Increases in left ventricular (LV) mass and concentric remodelling defined by increasing mass-to-volume (M:V) ratios are imaging risk markers for HFpEF. We aimed to determine if HGF is associated with adverse LV remodelling. Methods: We studied 4907 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), free of cardiovascular disease and HF at baseline, who had HGF measured and cardiac magnetic resonance imaging (CMR) performed at baseline. Of these, 2921 completed a second CMR at 10 years. We examined the cross-sectional and longitudinal associations of HGF and LV structural parameters using multivariable-adjusted linear mixed-effect models, adjusting for cardiovascular disease risk factors and N-terminal pro B-type natriuretic peptide. Results: The mean (SD) for age was 62 (10) years; 52% were female. Median (interquartile range) for HGF level was 890 pg/mL (745-1070). At baseline, the highest HGF tertile, compared to the lowest, was associated with a greater M:V ratio (relative difference 1.94 [95% confidence interval [CI]: 0.72, 3.17]) and lower LV end-diastolic volume (-2.07 mL [95% CI: -3.72, -0.42)]. In longitudinal analysis, the highest HGF tertile was associated with increasing M:V ratio (10-year difference: 4.68 [95% CI: 2.64, 6.72]) and decreasing LV end-diastolic volume (-4.74 [95% CI: -6.87, -2.62]). Conclusions: In a community-based cohort, higher HGF levels were independently associated with a concentric LV remodelling pattern of increasing M:V ratio and decreasing LV end-diastolic volume by CMR over 10 years. These associations may reflect an intermediate phenotype explaining the association of HGF with HFpEF risk.

Contexte: Le facteur de croissance des hépatocytes (hepatocyte growth factor; HGF) est une cytokine associée à l'insuffisance cardiaque (IC), particulièrement l'IC avec fraction d'éjection préservée (ICFEP). Une augmentation de la masse du ventricule gauche (VG) et un remodelage concentrique du VG, défini par une augmentation du ratio masse/volume (M:V), sont des marqueurs de risque d'ICFEP à l'examen d'imagerie. Nous souhaitions déterminer si le taux de HGF est associé à un remodelage préjudiciable du VG. Méthodologie: Nous avons étudié 4 907 participants à l'étude multiethnique sur l'athérosclérose (Multi-Ethnic Study of Atherosclerosis; MESA) qui, au départ, ne présentaient pas de maladie cardiovasculaire ni d'IC et pour qui le taux de HGF avait été mesuré et une imagerie cardiaque par résonance magnétique (IRMc) avait été réalisée. Parmi ces personnes, 2 921 ont subi une seconde IRMc à 10 ans. Nous avons examiné les associations intersectionnelles et longitudinales entre le taux de HGF et les paramètres structurels du VG à l'aide de modèles linéaires à effets mixtes multivariés, ajustés pour les facteurs de risque de maladie cardiovasculaire et les propeptides natriurétiques de type B N-terminal. Résultats: L'âge moyen des participants était de 62 ans (écart type : 10), et 52 % étaient des femmes. Le taux de HGF médian était de 890 pg/ml (écart interquartile : 745 à 1070). Au départ, comparativement au tertile inférieur du taux de HGF, le tertile supérieur était associé à un ratio M:V plus important (différence relative : 1,94; intervalle de confiance [IC] à 95 % : 0,72 à 3,17) et à un volume diastolique final du VG plus faible (-2,07 ml; IC à 95 % : -3,72 à -0,42). À l'analyse longitudinale, le tertile supérieur du taux de HGF était associé à un ratio M:V plus élevé (différence sur 10 ans : 4,68; IC à 95 % : 2,64 à 6,72) et à une réduction du volume diastolique final du VG (-4,74; IC à 95 % : -6,87 à -2,62). Conclusions: Dans une cohorte représentative de la population, un taux de HGF plus élevé était associé de manière indépendante à un schéma de remodelage concentrique du VG présentant une augmentation du ratio M:V et à une diminution du volume diastolique final du VG à l'IRMc sur 10 ans. Ces associations pourraient être représentatives d'un phénotype intermédiaire expliquant l'association entre le taux de HGF et le risque d'ICFEP.

Characteristics of Right Ventricular to Pulmonary Arterial Coupling and Association With Functional Status Among Older Aged Adults from the Multi-Ethnic Study of Atherosclerosis.

Although the echocardiographic:derived ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) is an important prognostic tool in heart failure (HF), the relation with 6-minute walk distance (6MWD) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) is less established. We sought to establish the normative values of TAPSE:PASP among older adults without cardiovascular disease (CVD) and evaluate the relation with NT-proBNP and 6MWD. Among 1,542 participants of the Multi-Ethnic Study of Atherosclerosis-HF ancillary study, the cross-sectional association of TAPSE:PASP with the outcomes of 6MWD and NT-proBNP was analyzed using multivariable linear regression, with progressive adjustment for sociodemographic and CVD risk factors. Our cohort had a mean age (SD) of 73 ± 8 years, 55% women, and a mean TAPSE:PASP ratio of 0.68 ± 0.16. In the unadjusted analysis, increasing tertiles of TAPSE:PASP were associated with younger age, less diabetes, higher estimated glomerular filtration rate, and less antihypertensive medication use. The TAPSE:PASP ratio significantly correlated with both 6MWD and NT-proBNP in the fully adjusted models. A 1-unit increment in TAPSE:PASP was associated with an adjusted 9.9% (4.8% to 15.2%) higher 6MWD, whereas a 1-unit increment in TAPSE:PASP was associated with an adjusted 38.0% (16.0% to 54.2%) lower NT-proBNP. There was a significant gender interaction of the association of TAPSE:PASP ratio and 6MWD, with stronger association seen in women. Among multiethnic older adults free of clinical CVD, the TAPSE:PASP ratio decreased with age, especially in women and was associated with decreased 6MWD and increasing NT-proBNP, the markers of subclinical HF.

Ideal Cardiovascular Health and Adipokine Levels: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: To evaluate the association between ideal cardiovascular health (CVH) and adipokine levels. Adipokines are hormones implicated in obesity and its cardiometabolic consequences. The concept of ideal CVH was introduced to promote 7 key health factors and behaviors in the general population. Previous studies have found strong associations between obesity and ideal CVH. However, existing literature on the link between CVH and adipokines is scarce. METHODS: We studied 1842 Multi-Ethnic Study of Atherosclerosis participants free of cardiovascular disease who had 7 CVH metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) measured at baseline and serum adipokine levels measured at a median of 2.4 years later. Each CVH metric was assigned a score of 0 (poor), 1 (intermediate), or 2 (ideal), and all scores were summed for a total CVH score (0-14). The total CVH scores of 0 to 8, 9 to 10, and 11 to 14 were considered inadequate, average, and optimal, respectively. We used multivariable linear regression models to assess the nonconcurrent associations between the CVH score and log-transformed adipokine levels. RESULTS: The mean age was 62.1 ± 9.8 years; 50.2% of participants were men. After adjusting for sociodemographic factors, a 1-unit higher CVH score was significantly associated with 4% higher adiponectin and 15% and 1% lower leptin and resistin levels. Individuals with optimal CVH scores had 27% higher adiponectin and 56% lower leptin levels than those with inadequate CVH scores. Similar trends were observed for those with average versus inadequate CVH scores. CONCLUSION: In a multi-ethnic cohort free of cardiovascular disease at baseline, individuals with average and optimal CVH scores had a more favorable adipokine profile than those with inadequate CVH scores.

Associations of urinary isoprostanes with measures of subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background: Urinary isoprostanes are markers of systemic oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC), thoracic aortic calcium (TAC) and carotid plaque are measure subclinical atherosclerosis and prognosticate ASCVD risk. We examined the associations between urinary isoprostane levels and measures of plaque prevalence, burden, incidence and progression across three vascular beds in a cohort from the Multi-Ethnic Study of Atherosclerosis. Methods: Urinary levels of 8-isoprostane and 2,3-dinor-8-F2-isoprostane were measured in 1089 participants (mean ± SD 62 ± 8 years, 48% women) at baseline. Participants underwent computed tomography for CAC and TAC, and duplex ultrasound for carotid plaque. TAC and CAC were reassessed at 2.4 and 10 years, respectively. Regression models were adjusted for CVD risk factors. Results: In adjusted models, there were no significant associations between isoprostane levels with CAC prevalence or progression. Highest versus lowest tertile of 8-isoprostane was associated with 28% lower prevalence of descending TAC at baseline [prevalence ratio (PR) 0.72 95% CI (0.56, 0.94)], while 1-SD higher 2,3-dinor-8-F2-isoprostane was associated with 96% higher incident ascending TAC at follow-up [Relative Risk 1.96 (1.24, 3.09)]. Highest versus lowest tertile of isoprostane measures were associated with 22% higher prevalence of carotid plaque [(PR 1.22 (1.04, 1.45)] and 14% difference [3,26] in greater extent of carotid plaque at baseline. Conclusions: Higher urinary isoprostanes were inconsistently associated with some measures of subclinical atherosclerosis by imaging. This suggests a limited role of urinary isoprostane levels as a prognostic marker for the development of ASCVD. Trial registration: The MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.

Trends and Outcomes of ST-Segment-Elevation Myocardial Infarction Among Young Women in the United States.

Background Although there has been a decrease in the incidence of ST-segment-elevation myocardial infarction (STEMI) in the United States, this trend might be stagnant or increasing in young women. We assessed the trends, characteristics, and outcomes of STEMI in women aged 18 to 55 years. Methods and Results We identified 177 602 women aged 18 to 55 with the primary diagnosis of STEMI from the National Inpatient Sample during years 2008 to 2019. We performed trend analyses to assess hospitalization rates, cardiovascular disease (CVD) risk factor profile, and in-hospital outcomes stratified by three age subgroups (18-34, 35-44, and 45-55 years). We found STEMI hospitalization rates were decreased in the overall study cohort from 52 per 100 000 hospitalizations in 2008 to 36 per 100 000 in 2019. This was driven by decreased proportion of hospitalizations in women aged 45 to 55 years (74.2% to-71.7%; P<0.001). Proportion of STEMI hospitalizationincreased in women aged 18-34 (4.7%-5.5%; P<0.001) and 35-44 years (21.2%-22.7%; P<0.001). The prevalence of traditional and non-traditional female-specific or female-predominant CVD risk factors increased in all age subgroups. The adjusted odds of in-hospital mortality in the overall study cohort and age subgroups were unchanged throughout the study period. Additionally, we observed an increase in the adjusted odds of cardiogenic shock, acute stroke, and acute kidney injury in the overall cohort over the study period. Conclusions STEMI hospitalizations are increasing among women aged <45 years, and in-hospital mortality has not changed over the past 12 years in women aged <55 years. Future studies on the optimization of risk assessment and management of STEMI in young women are urgently needed.

Adipokines and incident venous thromboembolism: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Obesity leads to adipocyte hypertrophy and adipokine dysregulation and is an independent risk factor for venous thromboembolism (VTE). However, the association between adipokines and VTE is not well established. OBJECTIVES: To examine whether adipokines are associated with increased risk of incident VTE. METHODS: We studied 1888 participants of the Multi-Ethnic Study of Atherosclerosis cohort who were initially free of VTE and had adipokine (adiponectin, leptin, and resistin) levels measured at either examination 2 or 3 (2002-2004 or 2004-2005, respectively). During follow-ups, VTE was ascertained through hospitalization records and death certificates by using ICD-9 and 10 codes. We used multivariable Cox proportional hazards regression to assess the association between 1 standard deviation (SD) log-transformed increments in adipokines and incident VTE. RESULTS: The mean ± SD age was 64.7 ± 9.6 years, and 49.8% of participants were women. Medians (interquartile range) of adiponectin, leptin, and resistin were 17.3 (11.8-26.2) mcg/mL, 13.5 (5.6-28.2) ng/mL, and 15.0 (11.9-19.0) ng/mL, respectively. There were 78 incident cases of VTE after a median of 9.7 (5.0-12.4) years of follow-up. After adjusting for sociodemographics, smoking, and physical activity, the hazard ratios (95% CIs) per 1 SD increment of adiponectin, leptin, and resistin were 1.14 (0.90-1.44), 1.29 (1.00-1.66), and 1.38 (1.09-1.74), respectively. The association for resistin persisted after further adjustments for body mass index and computed tomography-derived total visceral adipose tissue area. CONCLUSION: Higher resistin levels were independently associated with greater risk of incident VTE. Larger prospective cohort studies are warranted to confirm this association.

Association between parity and markers of inflammation: The multi-ethnic study of atherosclerosis.

Introduction: Multiparity has been associated with increased risk of cardiovascular disease (CVD). Inflammation may be a mechanism linking parity to CVD. We investigated the association between parity and later-life markers of inflammation. Methods: We studied 3,454 female MESA participants aged 45-84, free of CVD, who had data on parity and inflammatory markers. Parity was categorized as 0 (reference), 1-2, 3-4, or ≥5. Linear regression was used to evaluate the association between parity and natural log-transformed levels of fibrinogen, D-dimer, GlycA, high sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6). Results: Mean age was 62 ± 10 years. The proportion of women with nulliparity, 1-2, 3-4, and ≥5 live births were 18, 39, 29, and 14%, respectively. There was no association between parity and fibrinogen. Women with grand multiparity (≥5 live births) had 28, 10, and 18% higher levels of hsCRP, IL-6 and D-dimer, respectively, compared to nulliparous women, after adjustment for demographic factors. After additional adjustment for CVD risk factors, women with 1-2 and 3-4 live births had higher hsCRP and women with 1-2 live births had higher GlycA. Conclusion: In this diverse cohort of middle-to-older aged women, we found that higher parity was associated with some inflammatory markers; however, these associations were largely attenuated after adjustment for CVD risk factors. There was no clear dose-response relationship between parity and these inflammatory markers. Future studies are needed to evaluate how inflammation may influence the link between parity and CVD and whether healthy lifestyle/pharmacotherapies targeting inflammation can reduce CVD risk among multiparous women. Clinical trial registration: The MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.

Parity History and Later Life Sex Hormone Levels in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Multiparity is a risk factor for cardiovascular disease (CVD). A more androgenic sex hormone profile, with a higher testosterone (T)/estradiol (E2) ratio, is associated with worse CVD outcomes in women and might be one mechanism linking multiparity to increased CVD risk. We investigated the relationship between parity and sex hormones at mid-to-older age. METHODS: We performed a cross-sectional analysis of 2979 women with data on parity and endogenous sex hormone levels from the Multi-Ethnic Study of Atherosclerosis (MESA), a community-based cohort. Parity and gravidity (our exposures) were categorized as 0 (reference), 1-2, 3-4, or ≥ 5. Our outcome measures were T, E2, sex hormone binding globulin, dehydroepiandrosterone, and T/E2 ratio. Progressively adjusted linear regression was used to evaluate the association of parity/gravidity with sex hormones. RESULTS: In multivariable adjusted models, there were no significant associations of parity with E2, dehydroepiandrosterone, and sex hormone binding globulin. Compared with nulliparity, after adjustment for CVD risk factors, women with 1-2 and 3-4 live births had higher T, but this was not significant for grand multiparity (≥ 5 live births). However, grand multigravidity (≥ 5 pregnancies) was associated with 10% (95% confidence interval [CI], 1%-20%) higher T and 14% (95% CI, 1%-29%) higher T/E2, compared with null gravidity. Grand multiparity was associated with an 18% (95% CI, 4%-34%) higher T/E2 ratio compared with nulliparity, after adjustment for CVD risk factors. CONCLUSIONS: In this multiethnic cohort, women with grand multigravidity and grand multiparity had higher T/E2 levels, reflecting a more androgenic sex hormone profile. Longitudinal studies on sex hormones' influence on the relationship between multiparity and CVD are warranted.

Associations between endogenous sex hormones and FGF-23 among women and men in the Multi-Ethnic Study of Atherosclerosis.

Elevated levels of testosterone and fibroblast growth factor 23 (FGF-23) are both independently associated with a higher risk of cardiovascular disease (CVD). However, the relationship between sex hormones and FGF-23 is not well established. We explored the association between sex hormones and FGF-23 among middle-aged to older men and women in MESA. We studied 3,052 men and 2,868 postmenopausal women free of CVD at the time of enrollment with baseline serum sex hormones [total testosterone (T), free T, estradiol (E2) and sex hormone binding globulin (SHBG)] and intact FGF-23. In sex-stratified analyses, we examined the cross-sectional associations between log-transformed sex hormones (per 1 SD) and log-transformed FGF-23 using multiple linear regression adjusted for socio-demographics, CVD risk factors, estimated glomerular filtration rate and mineral metabolites (25-hydroxyvitamin D, calcium, phosphorus and parathyroid hormone). The mean (SD) age of study participants was 64 (10) years. The median (IQR) of FGF-23 was similar in women and men [38 (30-46) vs 38 (31-47) pg/mL]. In adjusted analyses, among women, 1 SD increment in free T was associated with 3% higher FGF-23 while SHBG was associated with 2% lower FGF-23. In men, 1 SD increment in E2 was associated with 6% higher FGF-23 whereas total T/E2 ratio was associated with 7% lower FGF-23. In conclusion, this exploratory analysis found that a more androgenic sex hormone profile was directly associated with FGF-23 in women and inversely associated with FGF-23 in men. Longitudinal studies are required to determine whether FGF-23 mediates the relationship between sex hormones and CVD risk.

A Systematic Review and Meta-Analysis of the Association Between Polycystic Ovary Syndrome and Coronary Artery Calcification.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine pathology affecting women of reproductive age characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Coronary artery calcification (CAC) is a marker of subclinical atherosclerosis and prognostic of cardiovascular disease (CVD) risk. Some studies have shown that women with PCOS have a greater risk of CAC; however, a few others report contrary findings. The objective of this study is to examine and quantify the association between PCOS and CAC. Materials and Methods: We searched EMBASE, Google Scholar, PubMed, and Web of Science from inception to November 2021 to identify studies that provided information on PCOS and CAC. We used a random-effects model to aggregate the odds ratios (ORs) for CAC (score >0) among women with PCOS compared with controls adjusted for sociodemographic characteristics and CVD risk factors. Results: From the 36 articles reviewed, 3 prospective cohort and 4 cross-sectional studies met the inclusion criteria with a total of 2341 participants. Six studies used CAC > 0 as an outcome and were included in the pooled analysis. Using the Hartung-Knapp-Sidik-Jonkman method, the pooled adjusted ORs for the associations between PCOS and the presence of CAC were 2.48 (95% confidence interval: 2.11-2.84) with no significant heterogeneity (I2 = 0.10%, p = 0.97) for the cohort studies and 1.88 (0.71-3.06) with no significant heterogeneity (I2 = 13.95%, p = 0.87) for the cross-sectional studies. Conclusion: In pooled analyses, women with PCOS had approximately twofold greater odds of having CAC compared with women without PCOS. However, additional prospective studies will be needed to further understand the relationship between PCOS and CAC.

Hepatocyte growth factor is associated with greater risk of extracoronary calcification: results from the multiethnic study of atherosclerosis.

BACKGROUND: Hepatocyte growth factor (HGF) is a biomarker with potential for use in the diagnosis, treatment and prognostication of cardiovascular disease (CVD). Elevated HGF is associated with calcification in the coronary arteries. However, knowledge is limited on the role HGF may play in extracoronary calcification (ECC). This study examined whether HGF is associated with ECC in the aortic valve (AVC), mitral annulus (MAC), ascending thoracic aorta and descending thoracic aortic (DTAC). METHODS: At baseline, adults aged 45-84 years, free of CVD, in the Multi-Ethnic Study of Atherosclerosis had HGF and ECC measured by ELISA and cardiac CT scan, respectively. ECC measurements were repeated after an average of 2.4 years of follow-up. Prevalent ECC was defined as Agatston score >0 at baseline. Incident ECC was defined as Agatston score >0 at follow-up among participants with Agatston score=0 at baseline. We used Poisson and linear mixed-effects regression models to estimate the association between HGF and ECC, adjusted for sociodemographic and CVD risk factors. RESULTS: Of 6648 participants, 53% were women. Mean (SD) age was 62 (10) years. Median (IQR) of HGF was 905 (757-1087) pg/mL. After adjustment for CVD risk factors, the highest HGF levels (tertile 3) were associated with greater prevalence and extent of AVC, MAC and DTAC at baseline compared with the lowest tertile (tertile 1). Additionally, the risk of incident AVC and MAC increased by 62% and 45%, respectively, in demographic-adjusted models. However, the associations were not statistically significant in fully adjusted models. The highest HGF levels were also associated with 10% and 13% increase in MAC and DTAC progression, respectively, even after adjustment for CVD risk factors. CONCLUSION: Higher HGF levels were significantly associated with a greater risk of calcification at some extracoronary sites, suggesting an alternate biological pathway that could be targeted to reduce CVD risk.

Favorable Cardiovascular Health Is Associated With Lower Prevalence, Incidence, Extent, and Progression of Extracoronary Calcification: MESA.

BACKGROUND: Ideal cardiovascular health (CVH) is associated with a lower incidence of cardiovascular disease. Extracoronary calcification (ECC)-measured at the aortic valve, mitral annulus, ascending thoracic aorta, and descending thoracic aorta-is an indicator of systemic atherosclerosis. This study examined whether favorable CVH was associated with a lower risk of ECC. METHODS: We analyzed data from MESA (Multi-Ethnic Study of Atherosclerosis) participants aged 45 to 84 years without cardiovascular disease at baseline. ECC was measured by noncontrast cardiac computed tomography scan at baseline and after an average of 2.4 years. Prevalent ECC was defined as an Agatston score >0 at the baseline scan. Incident ECC was defined as Agatston score >0 at the follow-up scan among participants with Agatston score of 0 at the baseline scan. Each CVH metric (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose) was scored 0 to 2 points, with 2 indicating ideal; 1, intermediate; and 0, poor. The aggregated CVH score was 0 to 14 points (0-8, inadequate; 9-10, average; 11-14, optimal). We used Poisson and linear mixed-effects regression models to examine the association between CVH and ECC adjusted for sociodemographic factors. RESULTS: Of 6504 participants, 53% were women with a mean age (SD) of 62 (10) years. Optimal and average CVH scores were associated with lower ECC prevalence, incidence, and extent. For example, optimal CVH scores were associated with 57%, 56%, 70%, and 54% lower risk of incident aortic valve calcification, mitral annulus calcification, ascending thoracic aorta calcification, and descending thoracic aorta calcification, respectively. In addition, optimal and average CVH scores were associated with lower ECC progression at 2 years, although these associations were only significant for mitral annulus calcification and descending thoracic aorta calcification. CONCLUSIONS: In this multiethnic cohort, favorable CVH was associated with a lower risk of extracoronary atherosclerosis. These findings emphasize the importance of primordial prevention as an intervention to reduce the burden of cardiovascular disease.

Glycemic Markers and Heart Failure Subtypes: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Although diabetes increases heart failure (HF) risk, it is unclear how various dysglycemia markers (hemoglobin A1C [HbA1C], fasting plasma glucose [FPG], homeostasis model assessment of insulin resistance, and fasting insulin) are associated with HF subtypes (HF with preserved ejection fraction [HFpEF] and HF with reduced ejection fraction [HFrEF]). We assessed the relation of markers of dysglycemia and risks of HFpEF and HFrEF. METHODS AND RESULTS: We included 6688 adults without prevalent cardiovascular disease who attended the first MESA visit (2000-2002) and were followed for incident hospitalized HF (HFpEF or HFrEF). Association of glycemic markers and status (normoglycemia, prediabetes, diabetes) with HFpEF and HFrEF were evaluated using adjusted Cox models. Over a median follow-up of 14.9 years, there were 356 HF events (145 HFpEF, 173 HFrEF, and 38 indeterminate HF events). Diabetes status conferred higher risks of HFpEF (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.57-2.68) and HFrEF (HR 2.02, 95% CI 1.38-2.97) compared with normoglycemia. Higher levels of FPG (≥126 mg/dL) and HbA1C (≥6.5%) were associated with similarly higher risks of HFpEF (HR for FPG 1.96, 95% CI 1.21-3.17; HR for HbA1C 2.00, 95% CI 1.20-3.31) and HFrEF (HR for FPG 1.84, 95% CI 1.18-2.88; HR for HbA1C 1.99, 95% CI 1.28-3.09) compared with reference values. Prediabetic range HbA1C (5.7%-6.4%) or FPG (100%-125 mg/dL), homeostasis model assessment of insulin resistance, and fasting insulin were not significantly associated with HFpEF or HFrEF. CONCLUSIONS: Among community-dwelling individuals, HbA1C and FPG in the diabetes range were each associated with higher risks of HFpEF and HFrEF, with similar magnitudes of their associations. LAY ABSTRACT: Heart failure (HF) has 2 major subtypes (the heart's inability to pump or to fill up). Diabetes is known to increase HF risk, but its effects and that of markers of high glucose levels (fasting blood glucose and hemoglobin A1C) on the occurrence of HF subtypes remains unknown. Among 6688 adults without known cardiovascular disease followed for nearly 15 years, diabetes conferred significantly higher risks of both HF types, compared with those with normal blood glucose levels. Higher levels of fasting blood glucose and hemoglobin A1C were similarly associated with higher risks of both types of HF.

Higher Leptin Levels Are Associated with Coronary Artery Calcium Progression: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Adipokines play a role in cardiometabolic pathways. Coronary artery calcium (CAC) progression prognosticates cardiovascular disease (CVD) risk. However, the association of adipokines with CAC progression is not well established. We examined the association of adipokines with CAC progression in a multi-ethnic cohort free of CVD at baseline. METHODS: We included 1,904 randomly-selected adults enrolled in the Multi-Ethnic Study of Atherosclerosis who had both adipokine levels [leptin, resistin, adiponectin] and CAC by CT measured at either exam 2 (2002-2004) or exam 3 (2004-2005). CAC was previously measured at exam 1 (2000-2002) and a subset (n=566) had CAC measured at exam 5 (2010-2012). We used logistic regression to examine odds of CAC progression between exam 1 and 2/3 (defined as >0 Agatston units of change/year). We used linear mixed effect models to examine CAC progression from exam 2/3 to 5. RESULTS: At exam 2/3, the mean age was 65(10) yrs; 50% women. In models adjusted for sociodemographic factors and BMI, the highest tertile of leptin, compared to lowest, was associated with an increased odds of CAC progression over the preceding 2.6yrs [OR 1.60 (95% CI: 1.10-2.33)]. In models further adjusted for visceral fat and CVD risk factors, the highest tertile of leptin was statistically significantly associated with a 4% (1-7%) greater CAC progression over an average of 7yrs. No associations were seen for resistin and adiponectin. CONCLUSIONS: Higher leptin levels were independently, but modestly, associated with CAC progression. Atherosclerosis progression may be one mechanism through which leptin confers increased CVD risk.

Associations of endogenous sex hormone levels with the prevalence and progression of valvular and thoracic aortic calcification in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Sex hormones (SH) may contribute to sex differences in cardiovascular disease (CVD). High free testosterone (T) and low sex hormone binding globulin (SHBG) have been associated with progression of coronary artery calcification in women. We now examined the association of SH with extra-coronary calcification (ECC) prevalence and progression among MESA participants. METHODS: We studied 2,737 postmenopausal women and 3,130 men free of clinical CVD with baseline SH levels. ECC measurements [ascending and descending thoracic aortic calcification (ATAC, DTAC), mitral annular calcification (MAC), aortic valve calcification (AVC)] were obtained by computed tomography at baseline and after 2.4 ± 0.9 years. We used multivariable Poisson regression to evaluate associations with ECC prevalence and incidence (Agatston scores >0) and linear mixed effects models for ECC progression, per 1-SD increment in log(SH) in women and men separately. RESULTS: The mean age was 65 ± 9 and 62 ± 10 years for women and men, respectively. In women, greater free T and lower SHBG were associated with MAC incidence in a demographic-adjusted model only. In men, lower free T was associated with MAC prevalence, DTAC incidence and progression, while greater SHBG was associated with MAC prevalence and DTAC progression after further adjusting for CVD risk factors. CONCLUSIONS: In this diverse cohort free of CVD, we found some associations of SH with ECC measures. In particular, free T was inversely associated with prevalent MAC and DTAC progression in men independent of CVD risk factors. SH may influence vascular calcification, but further work is needed to understand clinical implications of these findings.

The Association Between Multiparity and Adipokine Levels: The Multi-Ethnic Study of Atherosclerosis.

Background: Multiparity is a risk factor for cardiovascular disease (CVD). However, the mechanisms of this relationship are unknown. Adipokines may predispose multiparous women to certain cardiometabolic complications that can increase their risk of future CVD. Materials and Methods: We studied 973 female participants of the Multi-Ethnic Study of Atherosclerosis free of CVD, who had complete data on parity and adipokines measured at Examination 2 or 3 (randomly assigned). Parity was categorized as nulliparity, 1-2, 3-4, and ≥5 live births. Multivariable linear regression was used to evaluate the association of parity with leptin, resistin, and adiponectin levels. Results: The women had mean age of 65 ± 9 years. After adjustment for age, race/ethnicity, study site, education, menopause status, smoking, physical activity, use of hormone therapy, and waist circumference, a history of grand multiparity (≥5 live births) was associated with 11% higher resistin levels (95% confidence interval [CI] 0-23) and 3-4 live births was associated with 23% higher leptin levels (95% CI 7-42), compared with nulliparity. After adjustment for computed tomography-measured visceral fat, the association of 3-4 live births with leptin remained significant. There were no significant associations of parity with adipokines after further adjustment for additional CVD risk factors. Multigravidity (but not parity) was inversely associated with adiponectin levels. Conclusions: In a multiethnic cohort of women, greater parity was associated with resistin and leptin; however, this association was attenuated after accounting for CVD risk factors. Dysregulation of adipokines could contribute to the excess CVD risk associated with multiparity. Further studies are needed to determine whether adipokines independently mediate the relationship between multiparity and CVD. Clinical trials registration: The MESA cohort is registered at NCT00005487.

A systematic review of the bidirectional relationship between depressive symptoms and cardiovascular health.

Depression is a mental health disorder associated with a 2-fold increase in cardiovascular disease risk. However, the association between depression and cardiovascular health (CVH), as reflected by the American Heart Association's (AHA) CVH metrics, is incompletely understood. We aimed to systematically review the current evidence to understand and clarify whether a bidirectional relationship exists between depressive symptoms and CVH. We conducted a systematic review by searching EMBASE, Google Scholar, PubMed and Web of Science from inception to May 2021. MeSH terms and keywords were used to identify studies with information on depressive symptoms and CVH. Among 132 articles screened, 11 studies were included with 101,825 participants. Eight studies were cross-sectional while 3 studies used a prospective cohort design. Five studies found an association between participants with unfavorable CVH and depressive symptoms. Six studies found an association between participants with depressive symptoms and unfavorable CVH. In summary, we found a bidirectional relationship may exist between depressive symptoms and CVH. Further research is required to quantify the risk and identify the biological mechanisms underlying the association between depressive symptoms and unfavorable CVH so adequate screening and interventions can be directed towards people with depressive symptoms or unfavorable CVH.