Hard Cardiovascular Disease Research Articles

Ten-year trajectory of coronary artery calcification and risk of cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis.

Whether and how coronary artery calcium (CAC) progress contributes to cardiovascular outcomes has not been fully elucidated. The aim of this study was to identify different patterns of CAC change and evaluate the associations with different cardiovascular outcomes. Data from the Multi-Ethnic Study of Atherosclerosis study were analyzed. Participants with at least three CT measurements were included. The main study outcome is hard cardiovascular disease (CVD). CAC scores were determined as phantom-adjusted Agatston scores. A group-based trajectory model was used to identify latent groups and estimated the hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional regression models. A total of 3,616 participants were finally enrolled [mean age 60.55 (SD 9.54) years, 47.76% men and 39.30% Caucasian]. Four distinct trajectories in CAC were identified: class 1, low-stable (24.17%); class 2, low-increasing (27.60%); class 3, moderate-increasing (30.56%); and class 4, elevated-increasing (17.67%). During 13.58 (SD 2.25) years of follow-up, 291 cases of hard CVD occurred. The event rates of hard CVD per 1,000 person-years were 2.23 (95% CI 1.53-3.25), 4.60 (95% CI 3.60-5.89), 7.67 (95% CI 6.38-9.21) and 10.37 (95% CI 8.41-12.80) for classes 1-4, respectively. Compared to participants assigned to class 1, the full-adjusted HRs of hard CVD for classes 2-4 were 2.10 (95% CI 1.33-3.01), 3.17 (95% CI 2.07-4.87), and 4.30 (95% CI 2.73-6.78), respectively. The graded positive associations with hard CVD were consistently observed in subgroups of age, sex, and race, with the presence or absence of hypertension or diabetes. By analyzing potential risk factors for distinctive CAC trajectories, risk factors for the onset and progression of CAC could possibly differ: age, male sex, history of hypertension, and diabetes are consistently associated with the low-, moderate-, and elevated-increasing trajectories. However, Caucasian race, cigarette smoking, and a higher body mass index was related only to risk of progression but not to incident CAC. In this multi-ethnic population-based cohort, four unique trajectories in CAC change over a 10-year span were identified. These findings signal an underlying high-risk population and may inspire future studies on risk management.

Cardiovascular Risk Estimation Is Suboptimal in People With HIV.

Established cardiovascular disease (CVD) risk prediction functions may not accurately predict CVD risk in people with HIV. We assessed the performance of 3 CVD risk prediction functions in 2 HIV cohorts. CVD risk scores were calculated in the Mass General Brigham and Kaiser Permanente Northern California HIV cohorts, using the American College of Cardiology/American Heart Association atherosclerotic CVD function, the FHS (Framingham Heart Study) hard coronary heart disease function and the Framingham Heart Study hard CVD function. Outcomes were myocardial infarction or coronary death for FHS hard coronary heart disease function; and myocardial infarction, stroke, or coronary death for American College of Cardiology/American Heart Association and FHS hard CVD function. We calculated regression coefficients and assessed discrimination and calibration by sex; predicted to observed risk of outcome was also compared. In the combined cohort of 9412, 158 (1.7%) had a coronary heart disease event, and 309 (3.3%) had a CVD event. Among women, CVD risk was generally underestimated by all 3 risk functions. Among men, CVD risk was underestimated by the American College of Cardiology/American Heart Association and FHS hard CVD function, but overestimated by the FHS hard coronary heart disease function. Calibration was poor for women using the FHS hard CVD function and for men using all functions. Discrimination in all functions was good for women (c-statistics ranging from 0.78 to 0.90) and moderate for men (c-statistics ranging from 0.71 to 0.72). Established CVD risk prediction functions generally underestimate risk in people with HIV. Differences in model performance by sex underscore the need for both HIV-specific and sex-specific functions. Development of CVD risk prediction models tailored to HIV will enhance care for aging people with HIV.

Abstract P538: Relations of Left Ventricular Mass With Long-Term Cardiovascular and Health Outcomes: The Framingham Heart Study

Introduction: Although elevated left ventricular mass (LVM) is associated with increased risk for cardiovascular disease (CVD) events over short-term follow-up, limited data exists regarding echocardiographic assessments in relation to long-term health outcomes. Hypothesis: We assessed the associations of LVM to the risk of incident all-cause mortality, CVD, dementia, hypertension, diabetes, and chronic kidney disease (CKD) over 20 years of follow-up. Methods: We evaluated up to 3 serial echocardiographic observations (1991-2008) for up to 8218 Framingham Heart Study participants. We modeled LVM as indexed to height 2.7 , logarithmically transformed then standardized. Utilizing multivariable-adjusted time-dependent and interval-censored Cox proportional hazards models, we related log-LVMI to the incidence of CVD and other health outcomes through the end of 2019 by updating LVM and all covariates at multiple examinations. Results: Over a median follow-up of 17 years (max 29 years), our study participants (mean age 47 years, 54% women) experienced 1353 events for all-cause mortality, 948 for CVD, 293 for dementia, 1631 for hypertension, 492 for diabetes, and 627 for CKD. Higher log-LVMI was significantly associated with increased incident all-cause mortality and CVD, including its respective components: coronary heart disease, heart failure (with reduced and preserved ejection fraction), and stroke. Results were consistent for incident hard and atherosclerotic CVD. Higher LVMI was also significantly associated with increased incidence of dementia, hypertension, diabetes, and CKD (defined as eGFR<60 mL/min/1.73 m 2 and defined with urine albumin-to-creatinine ratio ≥30). Conclusions: In our large prospective community-based sample higher LVMI carries an adverse prognosis for multiple health outcomes over two decades of follow-up. These findings underscore the importance of maintaining an optimal LVM over the life course with control of its key determinants such as blood pressure and glycemia.

Abstract 14790: Association of Neighborhood Socioeconomic Disadvantage in Early Pregnancy and 30-Year Predicted Probability of Cardiovascular Disease 2-7 Years Postpartum

Introduction: To determine whether neighborhood socioeconomic disadvantage as measured by the Area Deprivation Index (ADI) in early pregnancy is associated with higher 30-year predicted risk of cardiovascular disease (CVD) by the Framingham Risk Score. Methods: A secondary analysis of data from the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study (HHS) longitudinal cohort. Participant home addresses in the first trimester were geocoded at the census-tract level. The exposure was neighborhood socioeconomic disadvantage using the 2015 ADI by tertile (least deprived [T1], reference; most deprived [T3]). The primary outcome was the predicted 30-year risk of hard CVD using the Framingham Risk Score (composite of fatal and non-fatal coronary heart disease and stroke). The secondary outcome was predicted 30-year risk of total CVD (composite of “hard” CVD plus coronary insufficiency and angina pectoris, stroke, transient ischemic attack, intermittent claudication and heart failure). Outcomes were assessed categorically as high-risk defined as a predicted probability of CVD > 10%, and secondarily as a continuous measure of absolute risk (%). Modified Poisson and linear regression models adjusted for age, insurance, education, and income. Results: Among 4,310 nulliparous individuals, the median age was 27 years (IQR: 23-31), and the median ADI was 43 (IQR: 22-74). At 2-7 years postpartum (median: 4 years), the median 30-year risk of hard CVD was 2.3% (IQR: 1.5-3.5), and total CVD was 5.5% (IQR: 3.7-7.9). Individuals living in neighborhoods in the highest tertile of socioeconomic disadvantage were more likely to have a high 30-year predicted risk of hard CVD (≥10%) compared with those in the lowest tertile (aRR: 2.25; 95% CI: 1.23, 4.11), with similar results for high 30-year predicted risk of total CVD (aRR: 1.36; 95% CI: 1.09, 1.69). Living in the highest ADI tertile was associated with a higher absolute risk of 30-year hard (adj. ß: 0.41; 95% CI: 0.19, 0.63) and total CVD (adj. ß: 0.76; 95% CI: 0.38, 1.14) when analyzed as a continuous outcome. Conclusions: Neighborhood socioeconomic disadvantage in early pregnancy is associated with higher predicted risk of 30-year CVD 2-7 years after delivery.

Abstract 14697: Developing a Machine Learning Algorithm Using Routine Clinical Data for the Detection of Hard Cardiovascular Disease Events

Introduction: Machine learning (ML) may enhance prediction of hard cardiovascular disease (CVD) events (e.g., myocardial infarction, stroke, cardiac arrest). Developing ML algorithms using routinely-collected clinical data offers a practical method to improve CVD event prediction. This study aimed to train ML algorithms to predict 10-year risk of hard CVD events using common clinical variables and compare performance to pooled cohort equations (PCEs). Hypothesis: ML algorithms trained on data from the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerotic Risk in Communities (ARIC) would outperform PCEs in predicting 10-year risk of hard CVD events when tested on a PCE-valid subset. Methods: Data from MESA and ARIC were obtained. Pooled baseline data were used for algorithm training. Patients with prior CVD or lacking 10-year follow-up were excluded. The primary endpoint was hard CVD event within 10 years of baseline. Variables of interest included patient history, anthropometry, and serum lipid levels. Cohort data was split into training (75%) and test (25%) sets. Models trained were neural network, gradient boost machine, k-nearest neighbors, and an ensemble model. Results: In total, 17,775 patients (5,703 MESA, 12,072 ARIC) with mean age of 56.2 ( + 8.2) years and 54.6% female were included. During the 10-year follow-up period, 1,344 (7.6%) had a first-time hard CVD event. The ensemble model had the highest AUC on the full test set (0.783 [95% CI 0.76-0.81]), followed by the gradient boosting machine (0.781 [0.76-0.81], neural network (0.780 [0.76-0.81]), and k-nearest neighbors (0.737 [0.71-0.76]). The gradient boosting machine demonstrated highest sensitivity (76.0%), while the ensemble had highest specificity (78.6%). In the PCE-valid subset, the ensemble model had the highest AUC (0.780 [0.75-0.81]) and outperformed PCE (AUC = 0.757 [0.73-0.78], p = 0.001), as did the gradient boosting machine (AUC = 0.779 [0.75-0.81], p = 0.003]) and neural network (AUC = 0.776 [0.75-0.80], p = 0.007). Conclusions: The ensemble, gradient boosting machine, and neural network improved prediction of hard CVD events over PCEs within a PCE-valid subset despite training on a broader cohort. Future studies should validate results on an external dataset.

Data-driven phenomapping for novel classification for cardiovascular outcomes compared with traditional obesity index: Tehran Lipid and Glucose Study

ObjectiveThis study aimed to propose a data-driven framework for classification of at-risk people for cardiovascular outcomes regarding obesity and metabolic syndrome.DesignA population-based prospective cohort study with a long-term follow-up.SettingData from...

Circulating ketone bodies and cardiovascular outcomes: the MESA study.

Ketone bodies (KB) are an important alternative metabolic fuel source for the myocardium. Experimental and human investigations suggest that KB may have protective effects in patients with heart failure. This study aimed to examine the association between KB and cardiovascular outcomes and mortality in an ethnically diverse population free from cardiovascular disease (CVD). This analysis included 6796 participants (mean age 62 ± 10 years, 53% women) from the Multi-Ethnic Study of Atherosclerosis. Total KB was measured by nuclear magnetic resonance spectroscopy. Multivariable-adjusted Cox proportional hazard models were used to examine the association of total KB with cardiovascular outcomes. At a mean follow-up of 13.6 years, after adjusting for traditional CVD risk factors, increasing total KB was associated with a higher rate of hard CVD, defined as a composite of myocardial infarction, resuscitated cardiac arrest, stroke, and cardiovascular death, and all CVD (additionally included adjudicated angina) [hazard ratio, HR (95% confidence interval, CI): 1.54 (1.12-2.12) and 1.37 (1.04-1.80) per 10-fold increase in total KB, respectively]. Participants also experienced an 87% (95% CI: 1.17-2.97) increased rate of CVD mortality and an 81% (1.45-2.23) increased rate of all-cause mortality per 10-fold increase in total KB. Moreover, a higher rate of incident heart failure was observed with increasing total KB [1.68 (1.07-2.65), per 10-fold increase in total KB]. The study found that elevated endogenous KB in a healthy community-based population is associated with a higher rate of CVD and mortality. Ketone bodies could serve as a potential biomarker for cardiovascular risk assessment.

Prognostic value of a left atrioventricular coupling index in pre- and post-menopausal women from the Multi-Ethnic Study of Atherosclerosis.

Sex hormones associated with both the left atrial (LA) and left ventricular (LV) structures in women, but the association of menopause status with left atrioventricular coupling is not established. To assess the prognostic value of a left atrioventricular coupling index (LACI) in peri-menopausal women without a history of cardiovascular disease (CVD). In all women participating in MESA study with baseline cardiovascular MRI, the LACI was measured as the ratio of the LA end-diastolic volume to the LV end-diastolic volume. Cox models were used to assess the association between the LACI and the outcomes of atrial fibrillation (AF), heart failure (HF), coronary heart disease (CHD) death, and hard CVD. Among the 2,087 women participants (61 ± 10 years), 485 cardiovascular events occurred (mean follow-up: 13.2 ± 3.3 years). A higher LACI was independently associated with AF (HR 1.70; 95%CI [1.51-1.90]), HF (HR 1.62; [1.33-1.97]), CHD death (HR 1.36; [1.10-1.68]), and hard CVD (HR 1.30; [1.13-1.51], all p < 0.001). Adjusted models with the LACI showed significant improvement in model discrimination and reclassification when compared to traditional models to predict: incident AF (C-statistic: 0.82 vs. 0.79; NRI = 0.325; IDI = 0.036), HF (C-statistic: 0.84 vs. 0.81; NRI = 0.571; IDI = 0.023), CHD death (C-statistic: 0.87 vs. 0.85; NRI = 0.506; IDI = 0.012), hard CVD (C-statistic: 0.78 vs. 0.76; NRI = 0.229; IDI = 0.012). The prognostic value of the LACI had a better discrimination and reclassification than individual LA or LV parameters. In a multi-ethnic population of pre- and post-menopausal women, the LACI is an independent predictor of HF, AF, CHD death, and hard CVD. [https://clinicaltrials.gov/], identifier [NCT00005487].

Abstract 9971: Distribution of Coronary Artery Calcium and Risk for Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis

Introduction: We tested the hypothesis that specific arteries with coronary artery calcium (CAC) would be associated with higher risk for incident cardiovascular disease (CVD) outcomes, even after accounting for traditional risk factors, and that adding this metric to current risk scores would improve event prediction. Methods: We analyzed data from 3,255 MESA participants with baseline CAC and event follow-up. Cox proportional hazards models assessed the independent associations between CAC presence in each of the main coronary arteries and incident myocardial infarction (MI), hard coronary artery disease (CHD), and hard CVD, adjusting for the ASCVD risk score and CAC volume and density. Area under the receiver operating characteristic curve (AUC) analyses assessed for risk discrimination by adding CAC distribution to existing risk models. Results: At baseline [mean age 66 years (SD 9.6); 1,893 female (58%)], 2,909 (89%) participants had CAC in the left anterior descending (LAD), 1,871 (58%) in the left circumflex (LCx), 1,691 (52%) in the right coronary artery (RCA), and 693 (21%) in the left main (LM). Over a median of 15.5 years, 275 developed MI, 408 CHD, and 598 CVD. After adjustment for the ASCVD risk score and CAC volume and density, only the RCA remained significant for MI and CHD, and was borderline for CVD (Table). AUC increased after adding RCA CAC presence to the ASCVD risk score for MI (0.5992 to 0.6660; 95% CI 0.031-0.102) and CHD (0.6483 to 0.6818; 95% CI, 0.003-0.064), but not for CVD, and there was no significant increase for any endpoints when added to models accounting for CAC volume and density. Conclusion: Prevalent CAC was most common in the LAD, followed by the LCx and RCA. Accounting for risk factors and CAC measures, the RCA was the only artery independently associated with additional MI and CHD risk. Moreover, MI and CHD risk prediction were improved with the addition of CAC distribution to the ASCVD score but not when also accounting for CAC volume and density.

Abstract 9969: Number of Calcified Coronary Arteries and Prediction of Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis

Introduction: Current coronary artery calcium (CAC) scoring methods do not account for the number of vessels affected. We assessed the hypothesis that the number of vessels with CAC would be associated with higher risk for incident cardiovascular disease (CVD) outcomes, even after accounting for traditional risk factors, and that adding this metric to current risk scores would improve event prediction. Methods: We analyzed data from 3,255 MESA participants with baseline CAC and event follow-up. Cox proportional hazard regression analyses evaluated the association between number of affected vessels and incident myocardial infarction (MI), hard coronary artery disease (CHD), and hard CVD, adjusting for the ASCVD score and CAC volume and density. Area under the receiver operator curves (AUC) assessed event discrimination by adding number of vessels with CAC to current risk models. Results: At baseline [mean age 66 years (SD 9.6); 1,893 female (58%)], 1,086 participants (33%) had CAC in 1 vessel, 832 in 2 (26%), 987 in 3 (30%), and 385 in 4 (12%). Over a median of 15.5 years, 275 developed MI, 408 CHD, and 598 CVD. Multivariable-adjusted risk was higher with CAC in 3-4 vs 1 vessel for all outcomes (Table) and with 3-4 vs 2-vessels for CHD and CVD (HR 1.36, 95% CI 1.0-1.8 and HR 1.30, 95% CI 1.0-1.6). AUC increased after adding the number of vessels with CAC to the ASCVD score for MI (0.5992 to 0.6645, p=0.002), but not for CHD or CVD, and there was no significant increase for any endpoint when added to models already accounting for CAC volume and density. Conclusions: In a cohort free of baseline CVD, CAC had similar prevalence in 1, 2, and 3 vessels. After accounting for the ASCVD score and CAC volume and density, CAC in 3-4 vessels still conferred a significantly higher risk for adverse CVD outcomes compared to CAC in 1-2 vessels. Moreover, MI risk prediction was improved with adding the number of vessels with CAC to the ASCVD score, but not when also accounting for CAC volume and density.

Prognostic value of a left atrioventricular coupling index (LACI) in pre- and post-menopausal women. from the multi-ethnic study of atherosclerosis (MESA)

Abstract Background Endogenous sex hormones associated with both the left atrial (LA) and left ventricular (LV) structures in peri-menopausal women, but the association of menopause status with left atrioventricular coupling is not well established. Purpose To assess the prognostic value of a left atrioventricular coupling index (LACI) in pre- and post-menopausal women without a history of cardiovascular disease (CVD) at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods In women participating in the MESA study, the LACI was measured as the ratio of the left atrial (LA) end-diastolic volume to the left ventricular (LV) end-diastolic volume using cardiovascular magnetic resonance (CMR). Cox proportional hazard models were used to assess the association between the LACI and the outcomes of atrial fibrillation (AF), heart failure (HF), and hard CVD defined by myocardial infarction, resuscitated cardiac arrest, stroke, or coronary heart disease death. Results Among the 2,087 women participants (61±10 years), 485 cardiovascular events were observed during the mean follow-up period of 13.2±3.3 years. A higher LACI was independently associated with AF (HR 1.70; 95% CI [1.51–1.90]), HF (HR 1.62; [1.33–1.97]), and hard CVD (HR 1.30; [1.13–1.51], all p&amp;lt;0.001). Adjusted models with the LACI showed significant improvement in model discrimination and reclassification when compared to currently used standard models used to predict the incidence of AF (C-statistic=0.82 vs. 0.79; NRI=0.325; IDI=0.036), HF (C-statistic=0.84 vs. 0.81; NRI=0.571; IDI=0.023), hard CVD (C-statistic=0.78 vs. 0.76; NRI=0.229; IDI=0.012). Conclusion In a multi-ethnic population of pre- and post-menopausal women, the LACI is an independent predictor of HF, AF, and hard CVD. In both pre- and post-menopausal women, the LACI has an incremental prognostic value for predicting cardiovascular events over traditional risk factors and sex hormone levels. ClinicalTrials: gov Identifier: NCT00005487 Funding Acknowledgement Type of funding sources: None.

Association between shift rotation and 30-year Framingham risk of cardiovascular disease among male workers in a medium-sized manufacturing factory.

Rotating shift work is associated with an increased risk of cardiovascular disease (CVD). This study compared the CVD risk score in 129 male line workers aged 22-49 years on different shifts in a medium-sized metal production factory from 2017 to 2020. We classified workers into four groups: permanent day shift, weekly rotation involving five consecutive nights, weekly rotation involving 3-4 consecutive nights, and monthly rotation involving two consecutive nights. We used the Framingham Risk Score to estimate the 30-yr risks of general and hard CVD (CVD risk estimates). We investigated the differences in CVD risk estimates between different groups using linear mixed models. The average 30-yr Framingham CVD risk estimates of each group ranged from 17.5% to 31.2% for general CVD and from 10.5% to 20.5% for hard CVD. Workers on weekly rotations involving 3-5 consecutive nights had 5%-10% significantly higher CVD risk estimates than workers on the permanent day shift. Workers on weekly rotations also had 6%-8% higher BMI-based CVD risk estimates than those on the monthly rotation involving two consecutive nights. While 24-h shift rotations are unavoidable, our findings underscored the potential CVD risk among workers on weekly rotations involving more consecutive nights.

Breast Arterial Calcification: a Novel Cardiovascular Risk Enhancer Among Postmenopausal Women.

Breast arterial calcification (BAC), a common incidental finding in mammography, has been shown to be associated with angiographic coronary artery disease and cardiovascular disease (CVD) outcomes. We aimed to (1) examine the association of BAC presence and quantity with hard atherosclerotic CVD (ASCVD) and global CVD; (2) ascertain model calibration, discrimination and reclassification of ASCVD risk; (3) assess the joint effect of BAC presence and 10-year pooled cohorts equations risk on ASCVD. A cohort study of 5059 women aged 60-79 years recruited after attending mammography screening between October 2012 and February 2015 was conducted in a large health plan in Northern California, United States. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Prespecified end points were incident hard ASCVD and a composite of global CVD. Twenty-six percent of women had BAC >0 mg. After a mean (SD) follow-up of 6.5 (1.6) years, we ascertained 155 (3.0%) ASCVD events and 427 (8.4%) global CVD events. In Cox regression adjusted for traditional CVD risk factors, BAC presence was associated with a 1.51 (95% CI, 1.08-2.11; P=0.02) increased hazard of ASCVD and a 1.23 (95% CI, 1.002-1.52; P=0.04) increased hazard of global CVD. While there was no evidence of dose-response association with ASCVD, a threshold effect was found for global CVD at very high BAC burden (95th percentile when BAC present). BAC status provided additional risk stratification of the pooled cohorts equations risk. We noted improvements in model calibration and reclassification of ASCVD: the overall net reclassification improvement was 0.12 (95% CI, 0.03-0.14; P=0.01) and the bias-corrected clinical-net reclassification improvement was 0.11 (95% CI, 0.01-0.22; P=0.04) after adding BAC status. Our results indicate that BAC has potential utility for primary CVD prevention and, therefore, support the notion that BAC ought to be considered a risk-enhancing factor for ASCVD among postmenopausal women.

Long-Term Prognostic Implications and Role of Further Testing in Adults Aged ≤55 Years With a Coronary Calcium Score of Zero (from the Multi-Ethnic Study of Atherosclerosis)

The long-term prognostic significance of a coronary artery calcium (CAC) score of 0 is poorly defined in younger adults. We evaluated this among participants aged 45 to 55years from the Multi-Ethnic Study of Atherosclerosis, and assessed whether additional biomarkers can identify subgroups at increased absolute risk. We included 1,407 participants (61% women) without diabetes or severe hypercholesterolemia, with estimated 10-year risk <20% and CAC=0. We evaluated all and hard cardiovascular disease (CVD) events, overall and among subjects with each of the following: high-sensitivity C-reactive protein levels ≥2mg/L, homocysteine ≥10µmol/L, high-sensitivity cardiac troponin T ≥95th percentile, lipoprotein (a) >50mg/dl, triglycerides ≥175mg/dl, apolipoprotein B ≥130mg/dl, albuminuria, thoracic aortic calcium, aortic valve calcium (AVC), mitral annular calcium, ankle-brachial index <0.9, any carotid plaque, and maximum internal carotid artery intima-media thickness (ICA-IMT) ≥1.5mm. Median follow-up was 16years, and overall CVD event rates were low (4% at 15years). For most exposures evaluated, rates of all CVD events were <6 per 1,000 person-years, except for ICA-IMT ≥1.5mm (6.43) and AVC (13.8). The number needed to screen to detect ICA-IMT ≥1.5mm was 8, and 84 for AVC. Among participants with borderline/intermediate risk or premature family history, hard CVD event rates were <7 per 1,000 for most exposures, except for ICA-IMT ≥1.5mm (8.25), albuminuria (8.30), and AVC (13.47). Nonsmokers and those with ICA-IMT <1.5mm had very low rates. In conclusion, our results demonstrate a favorable long-term prognosis of CAC=0 among adults aged ≤55 years, particularly among nonsmokers. ICA-IMT testing could be considered for further risk assessment in adults ≤55years with CAC=0 and uncertain management.

Ultra-processed foods and ten-year cardiovascular disease incidence in a Mediterranean population: results from a population-based cohort study

Abstract Background/Introduction Although cardiovascular disease (CVD) guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grain products, nuts and seeds, less attention has been given to the importance of minimizing ultra-processed foods, probably due to the paucity of studies that exist. Purpose The aim of the present work was to investigate the association between the consumption of ultra-processed foods and ten-year first fatal/non fatal CVD event in a sample from Greece. Methods A prospective study was conducted during 2001–2012 studying n=1,514 men and n=1,528 women (&amp;gt;18 years old) free of CVD. Baseline dietary assessment was based on a validated semi-quantitative food frequency questionnaire. Ultra-processed foods were defined according to a standardized procedure and included among others sweets and desserts, beverages, salty snacks, breakfast cereals and fast foods. Follow-up assessment of first fatal/non fatal CVD event (2011–2012) was achieved in n=2,020 participants (n=317 cases). Cox proportional hazards models were constructed to determine the multiadjusted association between ultra-processed food intake (energy-adjusted servings per week) and incident fatal/non fatal CVD. Results On average, participants consumed about 15 servings of ultra-processed foods per week. Ranking from 1st to 3rd ultra-processed food consumption tertile (low to high level of intake) CVD incidence was 8.1%, 12.2%, 16.6% (p=0.006). Each additional weekly serving of ultra-processed food was associated with 10% higher CVD risk within the decade (Hazard Ratio (HR)=1.10, 95% Confidence Interval (95% CI) (1.02, 1.21), p=0.04). This association was reexamined according to participants' level of adherence to a cardiac friendly dietary pattern i.e. Mediterranean diet (defined through MedDietScore, range 1–55). In particular, the aggravating effect of ultra-processed foods was retained and only slightly attenuated even in the subset of participants with moderate to high level of adherence to Mediterranean diet (defined as MedDietScore&amp;gt;27) (HRper 1 serving/week=1.08, 95% CI (0.98, 1.19), p=0.09). On the other side, it became even stronger in case of low level of adherence to this pattern (HRper 1 serving/week=1.19, 95% CI (1.12, 1.25), p=0.02). Conclusions Current findings support that even in a population with Mediterranean origins and easy access to healthy least processed choices, systematic consumption of ultra-processed foods on a weekly basis was associated with increased risk of hard CVD events. Tailor-made public health initiatives and nutrition policies are demanded to promote healthy and sustainable dietary patterns with less-processed foods of high nutritional value. Funding Acknowledgement Type of funding sources: None.

Long term prognostic implication of newly detected abnormal glucose tolerance among patients with stable cardiovascular disease: a population-based cohort study

BackgroundFasting plasma glucose (FPG) and 2-h post challenge plasma glucose (2 h-PCPG), whether as continuous or categorical variables, are associated with incident cardiovascular disease (CVD) and diabetes; however, their role among patients with existing CVD is a matter of debate. We aimed to evaluate associations of different glucose intolerance states with recurrent CVD and incident diabetes among subjects with previous CVD.MethodsFrom a prospective population-based cohort, 408 Iranians aged ≥ 30 years, with history of CVD and without known diabetes were included. Associations of impaired fasting glucose (IFG) according to the American Diabetes Association (ADA) and World Health Organization (WHO) criteria, impaired glucose tolerance (IGT), newly diagnosed diabetes (NDM) with outcomes of interest were determined by multivariable Cox proportional hazard models after adjustment for traditional risk factors. Furthermore, FPG and 2 h-PCPG were entered as continuous variables.ResultsOver a decade of follow-up, 220 CVD events including 89 hard events (death, myocardial infarction and stroke) occurred. Regarding prediabetes, only IFG-ADA was associated with increased risk of hard CVD [hazard ratio(HR), 95%CI: 1.62,1.03–2.57] in the age-sex adjusted model. In patients with NDM, those with FPG ≥ 7 mmol/L were at higher risk of incident CVD/coronary heart disease(CHD) and their related hard outcomes (HR ranged from 1.89 to 2.84, all P < 0.05). Moreover, those with 2 h-PCPG ≥ 11.1 mmol/L had significant higher risk of CVD (1.46,1.02–2.11), CHD (1.46,1.00–2.15) and hard CHD (1.95:0.99–3.85, P = 0.05). In the fully adjusted model, each 1 SD increase in FPG was associated with 20, 27, 15 and 25% higher risk of CVD, hard CVD, CHD and hard CHD, respectively; moreover each 1 SD higher 2 h-PCPG was associated with 21% and 16% higher risk of CVD, and CHD, respectively. Among individuals free of diabetes at baseline (n = 361), IFG-ADA, IFG-WHO and IGT were significantly associated with incident diabetes (all P < 0.05); significant associations were also found for FPG and 2 h-PCPG as continuous variables (all HRs for 1-SD increase > 2, P < 0.05).ConclusionsAmong subjects with stable CVD, NDM whether as high FPG or 2 h-PCPG, but not pre-diabetes status was significantly associated with CVD/CHD and related hard outcomes.

Breast Arterial Calcification and Cardiovascular Risk Among Postmenopausal Women

Background: Breast arterial calcification (BAC) is commonly seen in mammograms but considered an incidental finding. Prior studies have shown correlation of BAC with angiographic coronary artery disease and cardiovascular disease (CVD) outcomes. To shed light on the utility of BAC for primary prevention, we aimed to: 1) Examine the association of BAC presence and quantity with hard atherosclerotic CVD (ASCVD) and global CVD; 2) Ascertain improvement in model calibration, discrimination and reclassification of ASCVD risk; 3) Assess the joint effect of BAC presence and 10-year Pooled Cohorts Equation (PCE) risk on ASCVD. Methods: Cohort study of 5,059 women aged 60-79 years when they attended mammography screening (10/2012 - 2/2015) followed up for 6.5 years (SD=1.6 years). BAC status (presence vs. absence) and quantity (mg of calcium mass) were determined using digital mammograms. Findings: Twenty-six percent of women had BAC > 0 mg. BAC presence was associated with age, ethnicity, education level, diabetes, hypertension and parity. In adjusted Cox regression, BAC presence was associated with a 1.51 (95% CI, 1.08-2.11; p=0.02) increased hazard of ASCVD and a 1.23 (95% CI, 1.002-1.52; p=0.04) increased hazard of global CVD. There was evidence of dose-response associations and of additional risk stratification of the PCE risk by BAC status. We noted improvements in model calibration, discrimination and reclassification (22 to 28%) after adding BAC information. Interpretation: Our results add to the body of evidence that presence and quantity of BAC assessed with contemporary digital mammography has potential utility for primary CVD prevention among post-menopausal women. Funding: MINERVA is an investigator-initiated cohort study funded by the National Heart, Lung, and Blood Institute (RO1HL106-043; multiple PIs Iribarren and Molloi). Declaration of Interest: None to declare. Ethical Approval: The study was approved by the Institutional Review Boards of the participating institutions and all participants signed an informed consent.

Atherosclerotic Cardiovascular Disease in Rheumatoid Arthritis: Impact of Inflammation and Antirheumatic Treatment.

Patients with rheumatoid arthritis (RA) are at approximately 1.5-fold risk of atherosclerotic cardiovascular disease (CVD) compared with the general population, a phenomenon resulting from combined effects of traditional CVD risk factors and systemic inflammation. Rheumatoid synovitis and unstable atherosclerotic plaques share common inflammatory mechanisms, such as expression of proinflammatory cytokines interleukin (IL)-1, tumour necrosis factor (TNF)-α and IL-6. RA patients are undertreated in terms of CVD prevention, and structured CVD prevention programmes are warranted. Alongside management of traditional risk factors, suppressing systemic inflammation with antirheumatic medication is fundamental for the reduction of CVD risk among this high-risk patient group. Many antirheumatic drugs, especially methotrexate, TNF-α-inhibitors and IL-6-inhibitors are associated with reduced risk of CVD in observational studies among RA patients, but randomised controlled trials with hard CVD endpoints are lacking. In patients without rheumatic disease, anti-inflammatory therapies targeting nucleotide-binding oligomerisation domain, leucine-rich repeat and pyrin domain-containing protein 3 inflammasome and the IL-1/IL-6 pathway arise as potential therapies after an atherosclerotic CVD event.

Does Gender-Affirming Hormonal Treatment Affect 30-Year Cardiovascular Risk in Transgender Persons? A Two-Year Prospective European Study (ENIGI)

BackgroundCardiovascular (CV) implications of long-term gender affirming hormonal treatment (GAHT) in transgender individuals still remain largely unknown. AimTo evaluate changes in the 30-year Framingham cardiovascular disease (CVD) risk in a large cohort of transgender individuals after the start of GAHT. MethodsIn a multicenter prospective study, a consecutive series of 309 participants (165 transmen and 144 transwomen) was evaluated during a 2-year follow-up. Prospectively, after the start of GAHT a physical examination was performed and blood samples were drawn. CVD risk was calculated for each person, according to the Framingham 30-year CVD risk estimate. Main Outcome MeasureChanges in CV risk factors and 30-year Framingham CVD risk during GAHT. Clinical ImplicationsIn transmen testosterone-induced lipid profile alterations may have a clinical relevance on the individual long-term CVD risk. Strengths & LimitationsThe strength of the present study is the possibility to predict long-term CV outcomes in transgender individuals receiving GAHT based on a short observation; whereas the main limitation is that CVD risk prospective changes mainly represent the expression of risk factors changes during GAHT. ResultsIn transwomen a significant decrease in triglycerides, total cholesterol and LDL-cholesterol was observed during the 2-year follow-up (P < .05), whereas unfavorable lipid changes – such as increased total cholesterol, triglycerides, and LDL cholesterol levels and decreased HDL cholesterol levels (P < .05)- occurred after the start of GAHT in transmen. These changes in risk factors led to an increase in the risk of general and hard CVD events based on lipid profile over time in transmen (P = .001 and P = .005, respectively). No significant changes in general and hard CVD risk based on lipid profile were observed in transwomen over time. ConclusionsOur findings confirmed the unfavorable lipid changes in transmen after the start of GAHT even during a longer follow-up, empathizing the potential clinical impact of these modifications on individual long-term CVD risk.Cocchetti C, Castellini G, Iacuaniello D, et al. Does Gender-Affirming Hormonal Treatment Affect 30-Year Cardiovascular Risk in Transgender Persons? A Two-Year Prospective European Study (ENIGI). J Sex Med 2021;18:821–829.

Ultra-Processed Foods and Incident Cardiovascular Disease in the Framingham Offspring Study

BackgroundUltra-processed foods provide 58% of total energy in the U.S. diet, yet their association with cardiovascular disease (CVD) remains understudied. ObjectivesThe authors investigated the associations between ultra-processed foods and CVD incidence and mortality in the prospective Framingham Offspring Cohort. MethodsThe analytical sample included 3,003 adults free from CVD with valid dietary data at baseline. Data on diet, measured by food frequency questionnaire, anthropometric measures, and sociodemographic and lifestyle factors were collected quadrennially from 1991 to 2008. Data regarding CVD incidence and mortality were available until 2014 and 2017, respectively. Ultra-processed foods were defined according to the NOVA framework. The authors used Cox proportional hazards models to determine the multivariable association between ultra-processed food intake (energy-adjusted servings per day) and incident hard CVD, hard coronary heart disease (CHD), overall CVD, and CVD mortality. Multivariable models were adjusted for age, sex, education, alcohol consumption, smoking, and physical activity. ResultsDuring follow-up (1991 to 2014/2017), the authors identified 251, 163, and 648 cases of incident hard CVD, hard CHD, and overall CVD, respectively. On average, participants consumed 7.5 servings per day of ultra-processed foods at baseline. Each additional daily serving of ultra-processed foods was associated with a 7% (95% confidence interval [CI]: 1.03 to 1.12), 9% (95% CI: 1.04 to 1.15), 5% (95% CI: 1.02 to 1.08), and 9% (95% CI: 1.02 to 1.16) increase in the risk of hard CVD, hard CHD, overall CVD, and CVD mortality, respectively. ConclusionsThe current findings support that higher consumption of ultra-processed foods is associated with increased risk of CVD incidence and mortality. Although additional research in ethnically diverse populations is warranted, these findings suggest cardiovascular benefits of limiting ultra-processed foods.