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.

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.

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.

Hepatocyte Growth Factor and Incident Heart Failure Subtypes: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Hepatocyte growth factor (HGF) is a cytokine and marker of cardiovascular disease (CVD) risk. Less is known about HGF and incident heart failure (HF). We examined the association of HGF with incident HF and its subtypes in a multiethnic cohort. METHODS AND RESULTS: We included 6597 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, free of clinical CVD and HF at baseline, with HGF measured at baseline. Incident hospitalized HF was assessed and adjudicated for HF with preserved ejection fracture (HFpEF) vs HF with reduced ejection fraction (HFrEF). Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for HF risk by HGF levels, adjusted for socio-demographics, CVD risk factors and N-terminal pro-B-type natriuretic peptide. The mean age was 62 ± 10 years. The median HGF level was 950 pg/mL (interquartile range, 758-1086 pg/mL); 53% were women. Over 14 years (IQR, 11.5-14.7 years), there were 324 cases of HF (133 HFpEF and 157 HFrEF). For the highest HGF tertile compared with lowest, adjusted HRs were 1.59 (95% CI, 1.10-2.31), 1.90 (95% CI, 1.03-3.51), and 1.09 (95% CI, 0.65-1.82) for overall HF, HFpEF, and HFrEF, respectively. For continuous analysis per 1-standard deviation log-transformed HGF, adjusted HRs were 1.22 (95% CI, 1.06-1.41), 1.35 (95% CI, 1.09-1.69), and 1.00 (95% CI, 0.81-1.24) for HF, HFpEF, and HFrEF, respectively. CONCLUSIONS: HGF was independently associated with incident HF. HGF remained significantly associated with HFpEF but not HFrEF upon subtype assessment. Future studies should examine the mechanisms underlying these associations and evaluate whether HGF can be used to improve HF risk prediction or direct therapy.

Ideal cardiovascular health and resting heart rate in the Multi-Ethnic Study of Atherosclerosis.

Elevated resting heart rate (RHR) is associated with an increased cardiovascular disease (CVD) risk, but little is known about its association with cardiovascular health (CVH), assessed by the Life's Simple 7 (LS7) metrics. We explored whether ideal CVH was associated with RHR in a cohort free from clinical CVD. We conducted a cross-sectional analysis of baseline data (2000-2002) of 6457 Multi-Ethnic Study of Atherosclerosis participants in 2018. Each LS7 metric (smoking, physical activity, diet, body mass index, blood pressure, cholesterol and glucose) was scored 0-2. Total score ranged from 0 to 14. Scores of 0-8 indicate inadequate, 9-10 average, and 11-14 optimal CVH. RHR was categorized as <60, 60-69, 70-79 and ≥80 bpm. We used multinomial logistic regression to determine associations between CVH score and RHR, adjusting for age, sex, race/ethnicity, education, income, health insurance, and atrioventricular nodal blockers. Mean age of participants (standard deviation) was 62 (10) years; 53% were women; 47% had inadequate CVH, 33% average, and 20% optimal. Favorable CVH was associated with lower odds of having higher RHR. Compared to RHR <60 bpm, participants with optimal CVH had adjusted odds ratio (95% CI) of 0.55 (0.46-0.64) for RHR of 60-69 bpm, 0.34 (0.28-0.43) for 70-79 bpm, and 0.14 (0.09-0.22) for ≥80 bpm. A similar pattern was observed in the stratified analysis by sex, race/ethnicity and age. Favorable CVH was less likely to be associated with elevated RHR irrespective of sex, race/ethnicity and age. More research is needed to explore the usefulness of promoting ideal CVH to reduce elevated RHR, a known risk factor for CVD.

Association of Depression Risk with Patient Experience, Healthcare Expenditure, and Health Resource Utilization Among Adults with Atherosclerotic Cardiovascular Disease.

BACKGROUND: Approximately 20% of patients with atherosclerotic cardiovascular disease (ASCVD) suffer from depression. OBJECTIVE: To compare healthcare expenditures and utilization, healthcare-related quality of life, and patient-centered outcomes among ASCVD patients, based on their risk for depression (among those without depression), and those with depression (vs. risk-stratified non-depressed). DESIGN AND SETTING: The 2004-2015 Medical Expenditure Panel Survey (MEPS) was used for this study. PARTICIPANTS: Adults ≥ 18 years with a diagnosis of ASCVD, ascertained by ICD-9 codes and/or self-reported data. Individuals with a diagnosis of depression were identified by ICD-9 code 311. Participants were stratified by depression risk, based on the Patient Health Questionnaire-2. RESULTS: A total of 19,840 participants were included, translating into 18.3 million US adults, of which 8.6% (≈ 1.3 million US adults) had a high risk for depression and 18% had a clinical diagnosis of depression. Among ASCVD patients without depression, those with a high risk (compared with low risk) had increased overall and out-of-pocket expenditures (marginal differences of $2880 and $287, respectively, both p < 0.001), higher odds for resource utilization, and worse patient experience and healthcare quality of life (HQoL). Furthermore, compared with individuals who had depression, participants at high risk also reported worse HQoL and had higher odds of poor perception of their health status (OR 1.83, 95% CI [1.50, 2.23]) and poor patient-provider communication (OR 1.29 [1.18, 1.42]). LIMITATION: The sample population includes self-reported diagnosis of ASCVD; therefore, the risk of underestimation of the cohort size cannot be ruled out. CONCLUSION: Almost 1 in 10 individuals with ASCVD without diagnosis of depression is at high risk for it and has worse health outcomes compared with those who already have a diagnosis of depression. Early recognition and treatment of depression may increase healthcare efficiency, positive patient experience, and HQoL among this vulnerable population.

Multiparity is associated with poorer cardiovascular health among women from the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Multiparity is associated with a greater risk of incident cardiovascular disease. However, the relationship of parity with cardiovascular health, as measured by the American Heart Association Life's Simple 7 metrics, is uncertain. OBJECTIVE: We aimed to examine the association between parity and ideal cardiovascular health among 3430 women, aged 45-84 years, free of clinical cardiovascular disease enrolled in the Multi-Ethnic Study of Atherosclerosis. STUDY DESIGN: The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study that recruited middle-aged to older women and men from 6 centers in the United States between 2000 and 2002. The study population comprised 38% White, 28% Black, 23% Hispanic, and 11% Chinese American subjects. Parity (total number of live births) was self-reported and categorized as 0, 1-2, 3-4 and ≥5. The Life's Simple 7 metrics, defined according to American Heart Association criteria, include health behaviors (smoking, physical activity, body mass index, diet) and health factors (blood pressure, total cholesterol, and blood glucose). We categorized each metric into ideal (2 points), intermediate (1 point), and poor (0 points). A total cardiovascular health score of 0-8 was considered inadequate; 9-10, average; and 11-14, optimal. We used multinomial logistic regression to examine the cross-sectional association between parity and the cardiovascular health score, adjusted for sociodemographics, field site, hormone therapy, and menopause. RESULTS: The mean (standard deviation) age was 62 (10) years. The mean (standard deviation) cardiovascular health score was lower with higher parity (8.9 [2.3], 8.7 [2.3], 8.5 [2.2], and 7.8 [2.0] for 0, 1-2, 3-4, and ≥5 live births, respectively). In comparison to inadequate cardiovascular health scores, the adjusted odds of average cardiovascular health scores were significantly lower for all parity categories relative to nulliparity (prevalence odds ratios [OR] for parity of 1-2, 0.64 [95% confidence interval 0.49-0.83]; 3-4, 0.65 [0.49-0.86]; ≥5, 0.64 [0.45-0.91]). Women with ≥5 live births had a lower prevalence of optimal cardiovascular health scores (OR 0.50 [0.30-0.83]). In the fully adjusted models, the association between parity and each Life's Simple 7 metric was only statistically significant for body mass index. Women with ≥5 live births had lower prevalence of ideal body mass index (OR 0.52 [0.35-0.80]). In addition, the test for interaction showed that the association between parity and cardiovascular health was not modified by race/ethnicity (P = .81 for average cardiovascular health scores and P = .20 for optimal cardiovascular health scores). CONCLUSION: Multiparity was associated with poorer cardiovascular health, especially for women with ≥5 live births. More research is required to explore the mechanisms by which parity may worsen cardiovascular health.

A systematic review of the associations between HIV/HCV coinfection and biomarkers of cardiovascular disease.

The incidence of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection has been increasing with over 10 million people affected globally. The role biomarkers play as predictors of cardiovascular disease (CVD) risk among coinfected individuals is not well defined. We aimed to systematically review current evidence describing CVD biomarkers among individuals with HIV/HCV coinfection. We searched EMBASE, CINAHL, Google Scholar, PubMed, and Web of Science from inception to June 2017. MeSH terms and keywords were used to identify studies with information on HIV/HCV coinfection and CVD biomarkers (structural, functional, and serological) such as carotid intima-media thickness (CIMT), endothelial markers, C-reactive protein (CRP), homocysteine, and lipids. Among 332 articles screened, 28 were included (39,498 participants). Study designs varied: 18 cross-sectional, 9 cohort, and 1 clinical trial. Compared with healthy controls and people with HIV or HCV monoinfection, individuals with HIV/HCV coinfection had statistically significant lower levels of lipids and CRP and higher levels of endothelial markers (sICAM-1 and sVCAM-1), CIMT, homocysteine, and IL-6. One study found the odds of carotid plaque in coinfected individuals was 1.64 (0.91-2.94) compared with healthy controls, and another study showed the prevalence of vascular plaques (carotid and femoral) in coinfected individuals was higher compared with HIV monoinfected individuals (44% vs 14%, P = 0.04). Biomarkers of CVD have different patterns of association with HIV/HCV coinfection compared with monoinfection and healthy controls. Prospective studies are needed to confirm the predictive value of these biomarkers for clinical CVD risk among coinfected individuals.

Association between self-rated health and ideal cardiovascular health: The Baptist Health South Florida Employee Study.

Background: There is increasing evidence of the role psychosocial factors play as determinants of cardiovascular health (CVH). We examined the association between self-rated health (SRH) and ideal CVH among employees of a large healthcare organization. Methods: Data were collected in 2014 from employees of Baptist Health South Florida during an annual voluntary health risk assessment and wellness fair. SRH was measured using a self-administered questionnaire where responses ranged from poor, fair, good, very good to excellent. A CVH score (the proxy for CVH) that ranged from 0 to 14 was calculated, where 0-8 indicate an inadequate score, 9-10, average and 11-14, optimal. A multinomial logistic regression was used to examine the association between SRH and CVH. Results: Of the 9056 participants, 75% were female and mean age (SD) was 43 ± 12 years. The odds of having a higher CVH score increased as SRH improved. With participants who reported their health status as poor-fair serving as reference, adjusted odds ratios for having an optimal CVH score by the categories of SRH were: excellent, 21.04 (15.08-29.36); very good 10.04 (7.25-13.9); and good 3.63 (2.61-5.05). Conclusion: Favorable SRH was consistently associated with better CVH.

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.

Physician cardiovascular disease risk factor management: practice analysis in Japan versus the USA.

BACKGROUND: There is a 42% lower cardiovascular disease (CVD) death rate in Japan compared with the USA. Do physicians report differences in practice management of CVD risk factors in the two countries that might contribute to this difference? AIMS: CVD risk factor management reported by Japanese versus US primary care physicians was studied. METHODS: We undertook a descriptive study. An internet-based survey was conducted with physicians from each country. A convenience sample from the Shiga Prefecture in Japan and the state of Ohio in the USA resulted in 48 Japanese and 53 US physicians completing the survey. RESULTS: The survey group may not be representative of a larger sample. The survey demonstrated that 98% of responding Japanese physicians spend <10 minutes performing a patient visit, while 76% of US physicians spend 10 to 20 minutes (P < 0.0001) managing CVD risk factors. Eighty-seven percent of Japanese physicians (vs. 32% of US physicians) see patients in within three months for follow-up (P < 0.0001). Sixty-one percent of Japanese physicians allocate < 30% of visit time to patient education, whereas 60% of US physicians spend > 30% of visit time on patient education (P < 0.0001). Prescriptions are renewed very frequently by Japanese physicians (83% renewing less than monthly) compared with 75% of US physicians who renew medications every one to six months (P < 0.0001). Only 20% of Japanese physicians use practice guidelines routinely compared with 50% of US physicians (P = 0.0413). US physicians report disparities in care more frequently (P < 0.0001). Forty-three percent of Japanese (vs. 10% of US) physicians believe that they have relative freedom to practise medicine (P < 0.0001). CONCLUSION: Many factors undoubtedly affect CVD in different countries. The dominant ones include social determinants of health, genetics, public health and overall culture (which in turn determine diet, exercise and other factors). Yet the medical care system is an expensive component of society and its role in managing CVD risk factors deserves study. This descriptive report poses questions that require a more definitive study either with a more representative sample or direct observation of physician practices. US physicians responding to the survey reported greater administrative efforts, frustration and disparities in their practice, yet they followed practice guidelines more carefully. Japanese physicians responding reported focusing on quick, frequent visits that may have been more medication oriented, expecting more patient responsibility in self-care, which may have resulted in better chronic disease management. There may be differences in CVD risk factor management by primary care physicians in Japan versus the USA.

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.

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.

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.

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.

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.

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.

Associations between endogenous sex hormone levels and adipokine levels in the Multi-Ethnic Study of Atherosclerosis.

Background: Differences in sex hormone levels contribute to differences in cardiovascular disease (CVD) risk. Adipokines play a role in cardiometabolic pathways and have differing associations with CVD. Adipokine levels differ by sex; however, the association between sex hormone profiles and adipokines is not well established. We hypothesized that a more androgenic sex hormone profile would be associated with higher leptin and resistin and lower adiponectin levels among postmenopausal women, with the opposite associations in men. Methods: We performed an analysis of 1,811 adults in the Multi-Ethnic Study of Atherosclerosis who had both sex hormones and adipokines measured an average of 2.6 years apart. Sex hormones [Testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG), and dehydroepiandrosterone (DHEA)] were measured at exam 1; free T was estimated. Serum adipokines (leptin, resistin, adiponectin) were measured at exams 2 or 3. We used multivariable linear regression to examine the cross-sectional associations between sex hormones and adipokines. Results: The mean (SD) age was 63 (10) years, 48% were women; 59% non-White participants. For leptin, after adjusting for demographics only, higher free T and lower SHBG, were associated with higher leptin in women; this association was attenuated after further covariate adjustment. However in men, higher free T and lower SHBG were associated with greater leptin levels in fully adjusted models. For adiponectin, lower free T and higher SHBG were associated with greater adiponectin in both women and men after adjustment for CVD risk factors. For resistin, no significant association was found women, but an inverse association with total T and bioT was seen in men. Conclusion: Overall, these results further suggest a more androgenic sex profile (higher free T and lower SHBG) is associated with a less favorable adipokine pattern. These findings may provide mechanistic insight into the interplay between sex hormones, adipokines, and CVD risk.

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.