AI-enabled cardiac chambers volumetry in coronary artery calcium scans (AI-CACTM) predicts heart failure and outperforms NT-proBNP: The multi-ethnic study of Atherosclerosis.

INTRODUCTION: Coronary artery calcium (CAC) scans contain useful information beyond the Agatston CAC score that is not currently reported. We recently reported that artificial intelligence (AI)-enabled cardiac chambers volumetry in CAC scans (AI-CAC™) predicted incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA). In this study, we investigated the performance of AI-CAC cardiac chambers for prediction of incident heart failure (HF). METHODS: We applied AI-CAC to 5750 CAC scans of asymptomatic individuals (52% female, White 40%, Black 26%, Hispanic 22% Chinese 12%) free of known cardiovascular disease at the MESA baseline examination (2000-2002). We used the 15-year outcomes data and compared the time-dependent area under the curve (AUC) of AI-CAC volumetry versus NT-proBNP, Agatston score, and 9 known clinical risk factors (age, gender, diabetes, current smoking, hypertension medication, systolic and diastolic blood pressure, LDL, HDL for predicting incident HF over 15 years. RESULTS: Over 15 years of follow-up, 256 HF events accrued. The time-dependent AUC [95% CI] at 15 years for predicting HF with AI-CAC all chambers volumetry (0.86 [0.82,0.91]) was significantly higher than NT-proBNP (0.74 [0.69, 0.77]) and Agatston score (0.71 [0.68, 0.78]) (p â€‹< â€‹0.0001), and comparable to clinical risk factors (0.85, p â€‹= â€‹0.4141). Category-free Net Reclassification Index (NRI) [95% CI] adding AI-CAC LV significantly improved on clinical risk factors (0.32 [0.16,0.41]), NT-proBNP (0.46 [0.33,0.58]), and Agatston score (0.71 [0.57,0.81]) for HF prediction at 15 years (p â€‹< â€‹0.0001). CONCLUSION: AI-CAC volumetry significantly outperformed NT-proBNP and the Agatston CAC score, and significantly improved the AUC and category-free NRI of clinical risk factors for incident HF prediction.

Lipoprotein(a) and Long-Term Cardiovascular Risk in a Multi-Ethnic Pooled Prospective Cohort.

BACKGROUND: Lipoprotein(a) (Lp[a]) is a causal genetic risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited long-term follow-up data from large U.S. population cohorts. OBJECTIVES: This study examined the relationship of Lp(a) with ASCVD outcomes in a large, pooled, multi-ethnic U.S. METHODS: The study included data on Lp(a) and ASCVD outcomes from 5 U.S. PROSPECTIVE STUDIES: MESA (Multi-Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults), JHS (Jackson Heart Study), FHS-OS (Framingham Heart Study-Offspring), and ARIC (Atherosclerosis Risk In Communities). Lp(a) levels were classified on the basis of cohort-specific percentiles. Multivariable Cox regression related Lp(a) with composite incident ASCVD events by risk group and diabetes status. RESULTS: The study included 27,756 persons without previous ASCVD who were aged 20 to 79 years, including 55.0% women, 35.6% Black participants, and 7.6% patients with diabetes, with mean follow-up of 21.1 years. Compared with Lp(a) levels <50th percentile, Lp(a) levels in the 50th to <75th, 75th to <90th, and ≥90th percentiles had adjusted HRs of 1.06 (95% CI: 0.99-1.14), 1.18 (95% CI: 1.09-1.28), and 1.46 (95% CI: 1.33-1.59), respectively for ASCVD events. Elevated Lp(a) predicted incident ASCVD events similarly by risk group, sex, and race or ethnic groups, but more strongly in patients with vs without diabetes (interaction P = 0.0056), with HRs for Lp(a) levels ≥90th percentile of 1.92 (95% CI: 1.50-2.45) and 1.41 (95% CI: 1.28-1.55), respectively. Lp(a) also individually predicted myocardial infarction, revascularization, stroke, and coronary heart disease death, but not total mortality. CONCLUSIONS: The study shows, in a large U.S. pooled cohort, that higher Lp(a) levels are associated with an increased ASCVD risk, including in patients with diabetes.

AI-enabled left atrial volumetry in coronary artery calcium scans (AI-CACTM) predicts atrial fibrillation as early as one year, improves CHARGE-AF, and outperforms NT-proBNP: The multi-ethnic study of atherosclerosis.

BACKGROUND: Coronary artery calcium (CAC) scans contain actionable information beyond CAC scores that is not currently reported. METHODS: We have applied artificial intelligence-enabled automated cardiac chambers volumetry to CAC scans (AI-CACTM) to 5535 asymptomatic individuals (52.2% women, ages 45-84) that were previously obtained for CAC scoring in the baseline examination (2000-2002) of the Multi-Ethnic Study of Atherosclerosis (MESA). AI-CAC took on average 21 â€‹s per CAC scan. We used the 5-year outcomes data for incident atrial fibrillation (AF) and assessed discrimination using the time-dependent area under the curve (AUC) of AI-CAC LA volume with known predictors of AF, the CHARGE-AF Risk Score and NT-proBNP. The mean follow-up time to an AF event was 2.9 â€‹± â€‹1.4 years. RESULTS: At 1,2,3,4, and 5 years follow-up 36, 77, 123, 182, and 236 cases of AF were identified, respectively. The AUC for AI-CAC LA volume was significantly higher than CHARGE-AF for Years 1, 2, and 3 (0.83 vs. 0.74, 0.84 vs. 0.80, and 0.81 vs. 0.78, respectively, all p â€‹< â€‹0.05), but similar for Years 4 and 5, and significantly higher than NT-proBNP at Years 1-5 (all p â€‹< â€‹0.01), but not for combined CHARGE-AF and NT-proBNP at any year. AI-CAC LA significantly improved the continuous Net Reclassification Index for prediction of AF over years 1-5 when added to CHARGE-AF Risk Score (0.60, 0.28, 0.32, 0.19, 0.24), and NT-proBNP (0.68, 0.44, 0.42, 0.30, 0.37) (all p â€‹< â€‹0.01). CONCLUSION: AI-CAC LA volume enabled prediction of AF as early as one year and significantly improved on risk classification of CHARGE-AF Risk Score and NT-proBNP.

Thoracic versus coronary calcification for atherosclerotic cardiovascular disease events prediction.

This study compared the prognostic value of quantified thoracic artery calcium (TAC) including aortic arch on chest CT and coronary artery calcium (CAC) score on ECG-gated cardiac CT. METHODS: A total of 2412 participants who underwent both chest CT and ECG-gated cardiac CT at the same period were included in the Multi-Ethnic Study of Atherosclerosis Exam 5. All participants were monitored for incident atherosclerotic cardiovascular disease (ASCVD) events. TAC is defined as calcification in the ascending aorta, aortic arch and descending aorta on chest CT. The quantification of TAC was measured using the Agatston method. Time-dependent receiver-operating characteristic (ROC) curves were used to compare the prognostic value of TAC and CAC scores. RESULTS: Participants were 69±9 years of age and 47% were male. The Spearman correlation between TAC and CAC scores was 0.46 (p<0.001). During the median follow-up period of 8.8 years, 234 participants (9.7%) experienced ASCVD events. In multivariable Cox regression analysis, TAC score was independently associated with increased risk of ASCVD events (HR 1.31, 95% CI 1.09 to 1.58) as well as CAC score (HR 1.82, 95% CI 1.53 to 2.17). However, the area under the time-dependent ROC curve for CAC score was greater than that for TAC score in all participants (0.698 and 0.641, p=0.031). This was particularly pronounced in participants with borderline/intermediate and high 10-year ASCVD risk scores. CONCLUSION: Our study demonstrated a significant association between TAC and CAC scores but a superior prognostic value of CAC score for ASCVD events. These findings suggest TAC on chest CT provides supplementary data to estimate ASCVD risk but does not replace CAC on ECG-gated cardiac CT.

Epicardial and intra-thoracic adipose tissue and cardiovascular calcifications in type 1 diabetes (T1D) in epidemiology of diabetes Interventions and Complications (EDIC): A pilot study.

Objective: Coronary artery, aortic valve, and descending aorta calcification (CAC, AVC, DAC) are manifestations of atherosclerosis, and cardiac epicardial adipose tissue (EAT) indicates heart adiposity. This study explored the association between cardiac adipose tissue and cardiovascular calcification in participants with long-standing T1D. Methods: EAT and intra-thoracic adipose tissue (IAT) were measured in 100 T1D subjects with cardiac computed tomography (CT) scans in the EDIC study. Volume analysis software was used to measure fat volumes. Spearman correlations were calculated between CAC, AVC, DAC with EAT, and IAT. Associations were evaluated using multiple linear and logistic regression models. Results: Participants ranged in age from 32 to 57. Mean EAT, and IAT were 38.5 and 50.8 mm3, respectively, and the prevalence of CAC, AVC, and DAC was 43.6 %, 4.7 %, and 26.8 %, respectively. CAC was positively correlated with age (p-value = 0.0001) and EAT (p-value = 0.0149) but not with AVC and DAC; IAT was not associated with calcified lesions. In models adjusted for age and sex, higher levels of EAT and IAT were associated with higher CAC (p-value < 0.0001 for both) and higher AVC (p-values of 0.0111 and 0.0053, respectively), but not with DAC. The associations with CAC remained significant (p-value < 0.0001) after further adjustment for smoking, systolic blood pressure, BMI, and LDL, while the associations with AVC did not remain significant. Conclusion: In participants with T1D, higher EAT and IAT levels are correlated with higher CAC scores. EAT and IAT were not independently correlated with DAC or AVC.

Investigating peripheral blood monocyte and T-cell subsets as non-invasive biomarkers for asymptomatic hepatic steatosis: results from the Multi-Ethnic Study of Atherosclerosis.

Background: Circulating immune cells have gained interest as biomarkers of hepatic steatosis. Data on the relationships between immune cell subsets and early-stage steatosis in population-based cohorts are limited. Methods: This study included 1,944 asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis (MESA) with immune cell phenotyping and computed tomography measures of liver fat. Participants with heavy alcohol use were excluded. A liver-to-spleen ratio Hounsfield units (HU) <1.0 and liver attenuation <40 HU were used to diagnose liver fat presence and >30% liver fat content, respectively. Logistic regression estimated cross-sectional associations of immune cell subsets with liver fat parameters adjusted for risk factors. We hypothesized that higher proportions of non-classical monocytes, Th1, Th17, and memory CD4+ T cells, and lower proportions of classical monocytes and naive CD4+ T cells, were associated with liver fat. Exploratory analyses evaluated additional immune cell phenotypes (n = 19). Results: None of the hypothesized cells were associated with presence of liver fat. Higher memory CD4+ T cells were associated with >30% liver fat content, but this was not significant after correction for multiple hypothesis testing (odds ratio (OR): 1.31, 95% confidence interval (CI): 1.03, 1.66). In exploratory analyses unadjusted for multiple testing, higher proportions of CD8+CD57+ T cells were associated with liver fat presence (OR: 1.21, 95% CI: 1.02, 1.44) and >30% liver fat content (OR: 1.34, 95% CI: 1.07, 1.69). Conclusions: Higher circulating memory CD4+ T cells may reflect liver fat severity. CD8+CD57+ cells were associated with liver fat presence and severity, but replication of findings is required.

The Gut Microbial Metabolite Trimethylamine N-oxide, Incident CKD, and Kidney Function Decline.

BACKGROUND: Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite of dietary phosphatidylcholine and carnitine. Experimentally, TMAO causes kidney injury and tubulointerstitial fibrosis. Little is known about prospective associations between TMAO and kidney outcomes, especially incident CKD. We hypothesized that higher plasma TMAO levels would be associated with higher risk of incident CKD and greater rate of kidney function decline. METHODS: We included 10,564 participants from two community-based, prospective cohorts with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2 to assess incident CKD. TMAO was measured using targeted mass spectrometry at baseline and one follow-up visit. Creatinine and Cystatin C were measured up to 4 times during follow-up and used to compute eGFR. Incident CKD was defined as an eGFR decline ≥ 30% from baseline and a resulting eGFR<60 ml/min/1.73 m2. Time-varying Cox models assessed the association of serial TMAO measures with incident CKD, adjusting for sociodemographic, lifestyle, diet, and cardiovascular disease risk factors. Linear mixed models assessed the association with annualized eGFR change in 10,009 participants with at least one follow-up eGFR measure without exclusions for baseline eGFR levels. RESULTS: During a median follow-up of 9.4 years (interquartile range: 9.1-11.6 years), 979 incident CKD events occurred. Higher TMAO levels associated with higher risk of incident CKD (2nd to 5th vs. 1st quintile HR[95%CI]= 1.65 [1.22-2.23], 1.68 [1.26-2.25], 2.28 [1.72-3.02], and 2.24[1.68-2.98], respectively) and greater annualized eGFR decline ( 2nd to 5th vs. 1st quintile annualized eGFR change= -0.21 [-0.32, -0.09], -0.17 [-0.29, -0.05], -0.35 [-0.47, -0.22], and -0.43[-0.56, -0.30], respectively) with monotonic dose-response relationships. These associations were consistent across different racial/ethnic groups examined. The association with eGFR decline was similar to or larger than that seen for established CKD risk factors including diabetes, per 10 mmHg of higher systolic blood pressure, per 10 years of older age, and Black race. CONCLUSIONS: In community-based US adults, higher serial measures of plasma TMAO were associated with higher risk of incident CKD and greater annualized kidney function decline.

Comparison of risk profiles of participants in the Women's IschemiA TRial to reduce events in non-ObstRuctive CAD (WARRIOR) trial, using coronary computed tomography angiography vs invasive coronary angiography.

OBJECTIVE: To compare baseline characteristics of participants in the Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR) trial by qualification by Coronary Computed Tomography Angiography (CCTA) or Invasive Coronary Angiography (ICA). METHODS: The WARRIOR trial (NCT03417388) is an ongoing multicenter, prospective, randomized, blinded outcome evaluation of intensive medical therapy vs. usual care in women with suspected Ischemia and No Obstructive Coronary Artery Disease (INOCA) identified by either CCTA or ICA on the outcome of major adverse cardiovascular events (MACE). No coronary artery disease is defined as <50% luminal stenosis and normal coronary arteries is defined as no evidence of atherosclerosis including calcified and non-calcified plaque. Data presented was extracted on May 27, 2020. No clinical outcomes were assessed. RESULTS: An initial sample cohort of 797 women was included. The majority were younger than 65 years, White participants (73.3%), 159 had diabetes (19.9%), and 676 had angina (84.8%) with the remainder having symptoms of suspected ischemic heart disease. Over 50% of randomized participants had normal coronaries without luminal irregularities by ICA or CCTA. Participants randomized to ICA were more likely to have worse baseline clinical risk profiles with older age, higher burden of cardiac risk factors and poor quality of life with disabling angina. CONCLUSIONS: Among this initial sample of women with suspected INOCA randomized in the WARRIOR trial, there is a differential baseline cardiac risk of participants enrolled after CCTA or ICA. However, the majority had no evidence of atherosclerotic plaque or obstructive stenosis, after evaluation by ICA or CCTA. These results suggest that non-invasive evaluation with CCTA is likely to be associated with lower risk of MACE.

Trabecular bone mineral density as measured by thoracic vertebrae predicts incident hip and vertebral fractures: the multi-ethnic study of atherosclerosis.

We evaluated the relationship of bone mineral density (BMD) by computed tomography (CT), to predict fractures in a multi-ethnic population. We demonstrated that vertebral and hip fractures were more likely in those patients with low BMD. This is one of the first studies to demonstrate that CT BMD derived from thoracic vertebrae can predict future hip and vertebral fractures. PURPOSE/INTRODUCTION: Osteoporosis affects an enormous number of patients, of all races and both sexes, and its prevalence increases as the population ages. Few studies have evaluated the association between the vertebral trabecular bone mineral density(vBMD) and osteoporosis-related hip fracture in a multiethnic population, and no studies have demonstrated the predictive value of vBMD for fractures. METHOD: We sought to determine the predictive value of QCT-based trabecular vBMD of thoracic vertebrae derived from coronary artery calcium scan for hip fractures in the Multi-Ethnic Study of Atherosclerosis(MESA), a nationwide multicenter cohort included 6814 people from six medical centers across the USA and assess if low bone density by QCT can predict future fractures. Measures were done using trabecular bone measures, adjusted for individual patients, from three consecutive thoracic vertebrae (BDI Inc, Manhattan Beach CA, USA) from non-contrast cardiac CT scans. RESULTS: Six thousand eight hundred fourteen MESA baseline participants were included with a mean age of 62.2 ± 10.2 years, and 52.8% were women. The mean thoracic BMD is 162.6 ± 46.8 mg/cm3 (95% CI 161.5, 163.7), and 27.6% of participants (n = 1883) had osteoporosis (T-score 2.5 or lower). Over a median follow-up of 17.4 years, Caucasians have a higher rate of vertebral fractures (6.9%), followed by Blacks (4.4%), Hispanics (3.7%), and Chinese (3.0%). Hip fracture patients had a lower baseline vBMD as measured by QCT than the non-hip fracture group by 13.6 mg/cm3 [P < 0.001]. The same pattern was seen in the vertebral fracture population, where the mean BMD was substantially lower 18.3 mg/cm3 [P < 0.001] than in the non-vertebral fracture population. Notably, the above substantial relationship was unaffected by age, gender, race, BMI, hypertension, current smoking, medication use, or activity. Patients with low trabecular BMD of thoracic vertebrae showed a 1.57-fold greater risk of first hip fracture (HR 1.57, 95% CI 1.38-1.95) and a nearly threefold increased risk of first vertebral fracture (HR 2.93, 95% CI 1.87-4.59) compared to normal BMD patients. CONCLUSION: There is significant correlation between thoracic trabecular BMD and the incidence of future hip and vertebral fracture. This study demonstrates that thoracic vertebrae BMD, as measured on cardiac CT (QCT), can predict both hip and vertebral fractures without additional radiation, scanning, or patient burden. Osteopenia and osteoporosis are markedly underdiagnosed. Finding occult disease affords the opportunity to treat the millions of people undergoing CT scans every year for other indications.

Reference intervals for cardiometabolic risk factors in China: a national multicenter cross-sectional study on an adult population sample.

Background: The reference intervals (RIs) of adult blood lipid parameters currently used in China are not derived from the results of research in local populations and have not been adjusted for age and sex. In this study, we aimed to determine accurate RIs for blood lipid parameters and blood glucose (GluG) for Chinese adults using a national multicenter study. Methods: A total of 11,333 adults between 18 and 90 years of age were recruited in seven representative regions in China between June 2020 and December 2020. Hospitals participating in the study were regrouped into two geographical regions, southern China (Changsha, Chengdu, Hangzhou, and Nanning) and northern China (Beijing, Shenyang, and Ningxia), according to their geographical and administrative location. All samples were freshly collected and measured collectively in one laboratory on the Mindray full Automatic biochemical analyzer chemistry BS2000 analytical systems. Outliers were removed using the Tukey test. Three-level nested analysis of variance and scatter plot were used to explore the variations in sex, age, and region. Percentile curves of each indicator were plotted using the least mean square (LMS) method. The lower limit (2.5th percentile) and the upper limit (97.5th percentile) of the RI were determined by using nonparametric statistical methods. We also calculated the 90% confidence interval (CI) for the lower and upper limits. Results: A total of 8,283 participants were enrolled in the final analysis, with 3,593 (43.4%) men and 4,690 (56.6%) women. Regionality was observed in three analytes [small dense low density lipoprotein cholesterol (sd-LDLC), GluG, and apolipoprotein A1 (ApoA1)]. In northern China, the sd-LDLC and GluG levels in Shenyang were significantly higher than those in Ningxia and Beijing (P<0.05). In southern China, the sd-LDLC and GluG levels in Nanning were significantly higher than those in the three other cities (P<0.05), whereas the sd-LDLC and GluG levels in Chengdu were significantly lower than those in the three other cities (P<0.05). The level of ApoA1 in Chengdu was significantly higher than that in the three other cities. The homocysteine (HCY) level in male participants was clearly higher than that in female participants [ratio of standard deviation (SDR)sex =0.56], whereas the levels of high density lipoprotein cholesterol (HDLC) (SDRsex =0.40) and ApoA1 (SDRsex =0.27) in males were lower. The GluG and HCY level increased gradually with age. In females aged 45-55 years, there was an interesting change in scatter charts, where triglyceride (TG) and total cholesterol (TC) increased rapidly. We also found that for the age group of >55 years, the levels of TG and TC in females gradually surpassed those in males. Conclusions: The findings of this study may help establish age- and sex-specific reference values for the blood lipids of Chinese adults and serve as a valuable guide for the screening, diagnosis, treatment, prevention, and monitoring of cardiovascular disease (CVD).

Matrix Gla protein and the long-term incidence and progression of coronary artery and aortic calcification in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Matrix Gla protein (MGP) is an inhibitor of calcification that requires carboxylation by vitamin K for activity. The inactive form of MGP, dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP), has been associated with increased calcification. However, it is not known whether there is a longitudinal relationship between dephosphorylated-uncarboxylated matrix Gla protein levels and coronary and aortic calcification in large population cohorts. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) followed participants with serial cardiac computed tomography (CT) measures of vascular calcification. Dp-ucMGP was measured at baseline in a subset of participants who completed baseline and follow-up CTs approximately 10 years later and had available plasma specimens (n = 2663). Linear mixed effects models (LMMs) were used to determine the association of dp-ucMGP with the simultaneous incidence and progression of coronary artery, ascending thoracic aortic, or descending thoracic aortic calcification (CAC, ATAC, DTAC)]. RESULTS: For every one standard deviation (SD, 178 pmol/L) increment in dp-ucMGP, CAC increased by 3.44 ([95% CI = 1.68, 5.21], p < 0.001) Agatston units/year (AU/year), ATAC increased by 0.63 ([95% CI = 0.27, 0.98], p = 0.001) AU/year, and DTAC increased by 8.61 ([95% CI = 4.55, 12.67], p < 0.001) AU/year. The association was stronger for DTAC in those ≥65 years and with diabetes. CONCLUSIONS: We found a positive association of the inactive form of matrix Gla protein, dp-ucMGP, and long-term incidence/progression of CAC, ATAC, and DTAC. Future studies should investigate dp-ucMGP as a calcification regulator and MGP as a possible therapeutic target to slow progression of calcification in the vasculature.

Colchicine and plaque: A focus on atherosclerosis imaging.

Colchicine is an anti-inflammatory medication, classically used to treat a wide spectrum of autoimmune diseases. More recently, colchicine has proven itself a key pharmacotherapy in cardiovascular disease (CVD) management, atherosclerotic plaque modification, and coronary artery disease (CAD) treatment. Colchicine acts on many anti-inflammatory pathways, which translates to cardiovascular event reduction, plaque transformation, and plaque reduction. With the FDA's 2023 approval of colchicine for reducing cardiovascular events, a novel clinical pathway opens. This advancement paves the route for CVD management that synergistically merges lipid lowering approaches with inflammation inhibition modalities. This pioneering moment spurs the need for this manuscript's comprehensive review. Hence, this paper synthesizes and surveys colchicine's new role as an atherosclerotic plaque modifier, to provide a framework for physicians in the clinical setting. We aim to improve understanding (and thereby application) of colchicine alongside existing mechanisms for CVD event reduction. This paper examines colchicine's anti-inflammatory mechanism, and reviews large cohort studies that evidence colchicine's blossoming role within CAD management. This paper also outlines imaging modalities for atherosclerotic analysis, reviews colchicine's mechanistic effect upon plaque transformation itself, and synthesizes trials which assess colchicine's nuanced effect upon atherosclerotic transformation.

Coronary artery calcium and cardiovascular outcomes in patients with lymphoma undergoing autologous hematopoietic cell transplantation.

BACKGROUND: Patients undergoing autologous hematopoietic cell transplantation (HCT) have a >2-fold risk of developing cardiovascular disease (CVD; heart failure, myocardial infarction, and stroke), compared to the general population. Coronary artery calcium (CAC) is predictive of CVD in nononcology patients but is not as well studied in patients who underwent HCT and survivors of HCT.The objective of this study was to examine the association between CAC and CVD risk and outcomes after HCT in patients with lymphoma. METHODS: This was a retrospective cohort study of 243 consecutive patients who underwent a first autologous HCT for lymphoma between 2009 and 2014. CAC (Agatston score) was determined from chest computed tomography obtained <60 days from HCT. Multivariable Cox regression analysis was used to calculate hazard ratio (HR) estimates and 95% confidence intervals (CIs), adjusted for covariates (age, conventional risk factors [e.g., hypertension and dyslipidemia], and cancer treatment). RESULTS: The median age at HCT was 55.7 years (range, 18.5-75.1 years), 59% were male, and 60% were non-Hispanic White. The prevalence of CAC was 37%. The 5-year CVD incidence for the cohort was 12%, and there was an incremental increase in the incidence according to CAC score: 0 (6%), 1-100 (20%), and >100 (32%) (p = .001). CAC was significantly associated with CVD risk (HR, 3.0; 95% CI, 1.2-7.5) and worse 5-year survival (77% vs. 50%; p < .001; HR, 2.0; 95% CI, 1.1-3.4), compared to those without CAC. CONCLUSIONS: CAC is independently associated with CVD and survival after HCT. This highlights the importance of integrating readily available imaging information in risk stratification and decision-making in patients undergoing HCT, which sets the stage for strategies to optimize outcomes after HCT.

Closing the Last Mile Gap in Access to Multimodality Imaging in Rural Settings: Design of the Imaging Core of the Risk Underlying Rural Areas Longitudinal Study.

Achieving optimal cardiovascular health in rural populations can be challenging for several reasons including decreased access to care with limited availability of imaging modalities, specialist physicians, and other important health care team members. Therefore, innovative solutions are needed to optimize health care and address cardiovascular health disparities in rural areas. Mobile examination units can bring imaging technology to underserved or remote communities with limited access to health care services. Mobile examination units can be equipped with a wide array of assessment tools and multiple imaging modalities such as computed tomography scanning and echocardiography. The detailed structural assessment of cardiovascular and lung pathology, as well as the detection of extracardiac pathology afforded by computed tomography imaging combined with the functional and hemodynamic assessments acquired by echocardiography, yield deep phenotyping of heart and lung disease for populations historically underrepresented in epidemiological studies. Moreover, by bringing the mobile examination unit to local communities, innovative approaches are now possible including engagement with local professionals to perform these imaging assessments, thereby augmenting local expertise and experience. However, several challenges exist before mobile examination unit-based examinations can be effectively integrated into the rural health care setting including standardizing acquisition protocols, maintaining consistent image quality, and addressing ethical and privacy considerations. Herein, we discuss the potential importance of cardiac multimodality imaging to improve cardiovascular health in rural regions, outline the emerging experience in this field, highlight important current challenges, and offer solutions based on our experience in the RURAL (Risk Underlying Rural Areas Longitudinal) cohort study.

Factors Associated With Myocardial Infarction in a Rural Population With Peripheral Arterial Diseases.

Peripheral arterial disease (PAD) studies in rural populations are limited. The incidence of myocardial infarction (MI) is higher in patients with PAD. This study examined the association between sociodemographic and clinical risk factors and MI in patients with PAD in Central Appalachia, comprising of 230 counties across six states in the United States. Data from electronic medical records of 13,455 patients with PAD were extracted from a large health system in Central Appalachia. Bivariate and logistic regression analyses were conducted. The final sample consisted of 5574 patients with PAD, of whom 24.85% were also diagnosed with MI. The mean age was 71 ± 11.23 years, and the majority were male (56.40%). After adjusting for confounders, patients with hypertension had three times higher odds of MI (adjusted Odds Ratio [aOR] = 3.21; 95% CI: 2.50-4.14) compared with those without hypertension. The likelihood of MI increased by 51% among patients with diabetes (aOR = 1.51; 95% CI: 1.33-1.71), 34% among ever-smokers (aOR = 1.34; 95% CI: 1.18-1.52), and 45% in males (aOR = 1.45; 95% CI: 1.27-1.65). Hypertension, diabetes, smoking, and male sex were identified as significant risk factors for MI. Screening and effective management of these risk factors in rural areas could potentially prevent MI incidence among patients with PAD.

Testosterone therapy and the risk of cardiovascular disease in older, hypogonadal men.

The debate over the cardiovascular (CV) implications of testosterone therapy (TT) have resulted in diverging safety recommendations and clinical guidelines worldwide. This narrative review synthesizes and critically evaluates long-term studies examining the effects of TT within the context of aging, obesity, and endogenous sex hormones on CV disease (CVD) risk to support informed clinical decision-making. Observational studies have variably linked low endogenous testosterone with increased CVD risk, while randomized controlled trials (RCTs) demonstrate that TT yields cardiometabolic benefits without increasing short-term CV risk. The TRAVERSE trial, as the first RCT powered to assess CVD events, did not show increased major adverse cardiac events (MACE) incidence; however, its limitations - specifically the maintenance of testosterone at low-normal levels, a high participant discontinuation rate, and short follow-up - warrant a careful interpretation of its results. Furthermore, findings from the TTrials cardiovascular sub-study, which showed an increase in non-calcified plaque, indicate the need for ongoing research into the long-term CV impact of TT. The decision to initiate TT should consider the current evidence gaps, particularly for older men with known CVD. The CV effects of maintaining physiological testosterone levels through exogenous means remain to be fully explored. Until more definitive evidence is available, clinical practice should prioritize individualized care and informed discussions on the potential CV implications of TT.

Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in Coronary Artery Calcium >1,000.

BACKGROUND: Although a coronary artery calcium (CAC) of ≥1,000 is a subclinical atherosclerosis threshold to consider combination lipid-lowering therapy, differentiating very high from high atherosclerotic cardiovascular disease (ASCVD) risk in this patient population is not well-defined. OBJECTIVES: Among persons with a CAC of ≥1,000, the authors sought to identify risk factors equating with very high-risk ASCVD mortality rates. METHODS: The authors studied 2,246 asymptomatic patients with a CAC of ≥1,000 from the CAC Consortium without a prior ASCVD event. Cox proportional hazards regression modelling was performed for ASCVD mortality during a median follow-up of 11.3 years. Crude ASCVD mortality rates were compared with those reported for secondary prevention trial patients classified as very high risk, defined by ≥2 major ASCVD events or 1 major event and ≥2 high-risk conditions (1.4 per 100 person-years). RESULTS: The mean age was 66.6 years, 14% were female, and 10% were non-White. The median CAC score was 1,592 and 6% had severe left main (LM) CAC (vessel-specific CAC ≥300). Diabetes (HR: 2.04 [95% CI: 1.47-2.83]) and severe LM CAC (HR: 2.32 [95% CI: 1.51-3.55]) were associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95% CI: 0.7-0.9), although higher rates were observed for diabetes (1.4 [95% CI: 0.8-1.9]), severe LM CAC (1.3 [95% CI: 0.6-2.0]), and both diabetes and severe LM CAC (7.1 [95% CI: 3.4-10.8]). CONCLUSIONS: Among asymptomatic patients with a CAC of ≥1,000 without a prior index event, diabetes, and severe LM CAC define very high risk ASCVD, identifying individuals who may benefit from more intensive prevention therapies across several domains, including low-density lipoprotein-cholesterol lowering.