Coronary Artery Calcium for Risk Stratification Among Persons With Very High HDL Cholesterol.

Background: Compared to normal high-density lipoprotein (HDL) cholesterol values, very high HDL cholesterol is associated with a higher incidence of mortality and atherosclerotic cardiovascular disease (ASCVD). As such, clinical risk stratification among persons with very high HDL cholesterol is challenging. Objectives: Among persons with very high HDL cholesterol, the purpose was to determine the prevalence of coronary artery calcium (CAC) and compare the association between traditional risk factors vs CAC for all-cause mortality and ASCVD. Methods: The primary analysis was completed among 446 participants from the Cedars-Sinai Medical Center of the CAC Consortium with very high HDL cholesterol (≥77 mg/dL in men, ≥97 mg/dL in women). Cox proportional hazards regression assessed the association of CAC and traditional risk factors with all-cause mortality during a median follow-up of 10.7 years. Replication and validation analyses were performed for all-cause mortality among 119 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with very high HDL cholesterol, who also had information on incident ASCVD. Results: The mean age was 57.9 years old, 49% were women, and the median HDL cholesterol was 98 mg/dL. One-half of participants (50%) had prevalent CAC, in whom the median CAC score was 118. Prevalent CAC conferred a 3.6-fold higher risk of all-cause mortality (HR: 3.64; 95% CI: 1.21-11.01), which appeared to be a more robust predictor than individual traditional risk factors beyond age. In the validation sample, prevalent CAC but not individual traditional risk factors were associated with all-cause mortality (HR: 2.39; 95% CI: 1.07-5.34) and a 4.0-fold higher risk of ASCVD (HR: 4.06; 95% CI: 1.11-14.84). Conclusions: Measurement of CAC may facilitate clinical risk assessment among individuals with very high HDL cholesterol.

Predictors of incident stroke among individuals without coronary artery calcification: A pooled cohort analysis from the Multi-Ethnic Study of Atherosclerosis, Jackson Heart Study, and Framingham Heart Study.

INTRODUCTION: The absence of coronary artery calcium (CAC = 0) is associated with low risk of stroke events; however, predictors of incident stroke among those with CAC = 0 are not known. METHODS: Individual participant-level data were pooled from three prospective cohorts (Multi-Ethnic Study of Atherosclerosis, Jackson Heart Study, and Framingham Heart Study). Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors and incident adjudicated stroke among individuals with CAC = 0 who were free of clinical atherosclerotic cardiovascular disease at baseline. RESULTS: Among 6180 participants (mean age 53 [SD 11] years, 62% women, and 44% White, 36% Black, and 20% other individuals), over a median (IQR) follow up of 15 (12-16) years, there were 122 strokes (95 ischemic, 27 hemorrhagic) with an overall unadjusted event rate of 2.0 per 1000 person-years. After multivariable adjustment, risk factors associated with overall stroke included (hazard ratio [95% CI]) systolic blood pressure (SBP): 1.19 (1.05-1.36) per 10-mmHg increase and carotid intima-media thickness (CIMT): 1.21 (1.04-1.42) per 0.1-mm increment. Current cigarette smoking: 2.68 (1.11-6.50), SBP: 1.23 (1.06-1.42) per 10-mmHg increase, and CIMT: 1.25 (1.04-1.49) per 0.1-mm increment were associated with ischemic stroke, whereas C-reactive protein was associated with hemorrhagic stroke risk (0.49, 0.25-0.93). CONCLUSION: In a large cohort of individuals with CAC = 0, the rate for incident stroke was low (2.0 per 1000-person years) and was associated with modifiable risk factors.

Branched-Chain Amino Acids, Alanine, and Thyroid Function: A Cross-Sectional, Nuclear Magnetic Resonance (NMR)-Based Approach from ELSA-Brasil.

The association of thyroid function with essential and non-essential amino acids is understudied, despite their common metabolic roles. Thus, our aim was to evaluate the association of thyroid function with the levels of branched-chain amino acids (BCAAs-leucine, isoleucine, and valine) and of alanine in the general population. We utilized data from the São Paulo research center of ELSA-Brasil, a longitudinal population-based cohort study. Thyroid parameters included thyroid stimulating hormone (TSH), free T4 and free T3 levels, and the FT4:FT3 ratio. BCAAs and alanine were analyzed on a fully automated NMR platform. The current analysis included euthyroid participants and participants with subclinical hyperthyroidism and hypothyroidism. We used Pearson's coefficient to quantify the correlation between thyroid-related parameters and amino acids. Linear regression models were performed to analyze whether thyroid parameters were associated with BCAAs and alanine levels. We included 4098 participants (51.3 ± 9.0 years old, 51.5% women) in this study. In the most adjusted model, higher levels of TSH were associated with higher levels of alanine, FT4 levels were inversely associated with isoleucine levels, FT3 levels were statistically significant and positively associated with valine and leucine, and the T3:T4 ratio was positively associated with all amino acids. We observed that subclinical hypothyroidism was positively associated with isoleucine and alanine levels in all models, even after full adjustment. Our findings highlight the association of subclinical hypothyroidism and thyroid-related parameters (including TSH, free T4, free T3, and FT4:FT3 ratio) with BCAAs and alanine. Further studies are needed to explore the mechanisms underlying this association. These insights contribute to our understanding of the influence of thyroid-related parameters on BCAA and alanine metabolism.

Associations of Dietary Calcium and Phosphorus With Vascular and Valvular Calcification: The ARIC Study.

Background: High dietary calcium and phosphorus may accelerate vascular calcification, but epidemiological data are inconsistent. Most of those studies assessed diet at one point and have not been systematically evaluated. Objectives: The purpose of this study was to assess the associations of dietary calcium and phosphorus intakes in middle age with coronary artery and extra-coronary calcification at older age. Methods: We studied 1,914 participants from the ARIC (Atherosclerosis Risk In Communities) study (mean age 80.5 years) without coronary heart disease who underwent chest computed tomography scans at visit 7 (2018-2019) and completed a 66-item food frequency questionnaire at 2 earlier visits (visit 1 [1987-1989] and visit 3 [1993-1995]). Dietary calcium and phosphorus intakes were averaged between these 2 visits. Calcification was quantified by the Agatston score in coronary artery, ascending aorta, descending aorta, aortic valve ring, aortic valve, and mitral valve. Results: Dietary calcium intake was inversely associated with coronary artery and ascending aorta calcification, whereas the association was not significant for other measures of extra-coronary calcification. For example, the highest vs lowest quartile of calcium intake showed an adjusted OR of 0.66 (95% CI: 0.45-0.98) for coronary artery calcification (Agatston score ≥75th percentile). Dietary phosphorus intake demonstrated similar results, but the magnitude of the association was weaker than dietary calcium intake. Conclusions: Dietary calcium and phosphorus intakes at middle age were not positively associated with vascular and valvular calcification at over 75 years old. Our findings did not support the link between a calcium or phosphorus-rich diet and vascular and valvular calcification.

Coronary Atherosclerotic Plaque Burden Assessment by Computed Tomography and Its Clinical Implications.

Recent studies have demonstrated that coronary plaque burden carries greater prognostic value in predicting adverse atherosclerotic cardiovascular disease outcomes than myocardial ischemia, thereby challenging the existing paradigm. Advances in plaque quantification through both noncontrast and contrast-enhanced computed tomography (CT) methods have led to earlier and more cost-effective detection of coronary disease compared with traditional stress testing. The 2 principal techniques of noninvasive coronary plaque quantification assessment are coronary artery calcium scoring by noncontrast CT and coronary CT angiography, both of which correlate with disease burden on invasive angiography. Plaque quantification from these imaging modalities has shown utility in risk stratification and prognostication of adverse cardiovascular events, leading to increased incorporation into clinical practice guidelines and preventive care pathways. Furthermore, due to their expanding clinical value, emerging technologies such as artificial intelligence are being integrated into plaque quantification platforms, placing more advanced measures of plaque burden at the forefront of coronary plaque evaluation. In this review, we summarize recent clinical data on coronary artery calcium scoring and coronary CT angiography plaque quantification in the evaluation of adverse atherosclerotic cardiovascular disease in patients with and without chest pain, highlight how these methods compare to invasive quantification approaches, and directly compare the performance characteristics of coronary artery calcium scoring and coronary CT angiography.

Low-density lipoprotein-cholesterol and subclinical coronary atherosclerosis in a middle-aged asymptomatic U.S. population: The Miami Heart Study at Baptist Health South Florida.

BACKGROUND AND AIMS: We aimed to investigate the interplay between low-density lipoprotein-cholesterol (LDL-C) and coronary plaque in asymptomatic cohorts undergoing coronary tomography angiography (CCTA) assessment in the United States. METHODS: A cross-sectional analysis of baseline data from 1808 statin-naïve participants in the Miami Heart Study was conducted. We assessed CCTA-detected atherosclerosis (any plaque, noncalcified plaque, maximal stenosis ≥50%, high-risk plaque) across LDL-C levels, coronary artery calcium (CAC) scores (0, 1-99, ≥100), and 10-year cardiovascular risk categories. RESULTS: Atherosclerosis presence varied across LDL-C levels: 40% of those with LDL-C ≥190 mg/dL had no coronary plaque, while 33% with LDL-C <70 mg/dL had plaque (22.4% with noncalcified plaque). Among those with CAC 0, plaque prevalence ranged from 13.2% (LDL-C <70 mg/dL) to 28.2% (LDL-C ≥190 mg/dL), noncalcified plaque from 13.2% to 25.6%, stenosis ≥50% from 0 to 2.6%, and high-risk plaque from 0 to 5.1%. Conversely, with CAC ≥100, all had coronary plaque, with noncalcified plaque prevalence ranging from 25.0% (LDL-C <70 mg/dL) to 83.3% (LDL-C ≥190 mg/dL), stenosis ≥50% from 25.0% to 50.0%, and high-risk plaque from 0 to 66.7%. Among low-risk participants, 76.7% had CAC 0, yet 31.5% had any plaque and 18.3% had noncalcified plaque. Positive trends between LDL-C and any plaque (17.9%-45.2%) or noncalcified plaque (12.8%-23.8%) were observed in the low-risk group, but no clear trends were seen in higher-risk groups. CONCLUSIONS: Heterogeneity exists in subclinical atherosclerosis across LDL-C, CAC, and estimated cardiovascular risk levels. The value of CCTA in risk-stratifying asymptomatic adults should be further explored.

The Princeton IV Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease.

The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative symposium dedicated to optimizing sexual function and preserving cardiovascular health. The Fourth Princeton Consensus Conference was convened on March 10-11, 2023, at the Huntington Medical Research Institutes in Pasadena, California. Princeton panels I to III addressed the clinical management of men with erectile dysfunction (ED) who also had cardiovascular disease. Thirteen years since Princeton III, Princeton IV builds on previous foundations in several key areas. Mounting evidence supports the need for providers to treat men with ED as being at risk for cardiac events until proven otherwise. Algorithms for the diagnosis and treatment of ED are updated with new recommendations for coronary artery calcium scoring for advanced cardiovascular risk stratification. Optimization of oral phosphodiesterase type 5 inhibitors in the treatment of men with ED and cardiovascular disease is thoroughly explored, including recent evidence of potential cardioprotective effects of these drugs.

National and State Estimates of SELECT Trial Eligibility and Its Public Health Impact in the US.

This cross-sectional study of US adults examines the geographical distribution of individuals eligible to participate in the Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial to estimate potential cardiovascular health impacts of implementing the trial findings at state and national levels.

Lipoprotein(a) and Coronary Plaque in Asymptomatic Individuals: The Miami Heart Study at Baptist Health South Florida.

BACKGROUND: Elevated levels of lipoprotein(a) (Lp(a)) are independently associated with an increased risk of atherosclerotic cardiovascular disease events. However, the mechanisms driving this association are poorly understood. We aimed to evaluate the association between Lp(a) and coronary plaque characteristics in a contemporary US cohort without clinical atherosclerotic cardiovascular disease, undergoing coronary computed tomography angiography, the noninvasive gold standard for the assessment of coronary atherosclerosis. METHODS: We used baseline data from the Miami Heart Study-a community-based, prospective cohort study-which included asymptomatic adults aged 40 to 65 years evaluated using coronary computed tomography angiography. Those taking any lipid-lowering therapies were excluded. Elevated Lp(a) was defined as ≥125 nmol/L. Outcomes included any plaque, coronary artery calcium score >0, maximal stenosis ≥50%, presence of any high-risk plaque feature (positive remodeling, spotty calcification, low-attenuation plaque, napkin ring), and the presence of ≥2 high-risk plaque features. RESULTS: Among 1795 participants (median age, 52 years; 54.3% women; 49.6% Hispanic), 291 (16.2%) had Lp(a) ≥125 nmol/L. In unadjusted analyses, individuals with Lp(a) ≥125 nmol/L had a higher prevalence of all outcomes compared with Lp(a) <125 nmol/L, although differences were only statistically significant for the presence of any coronary plaque and ≥2 high-risk features. In multivariable models, elevated Lp(a) was independently associated with the presence of any coronary plaque (odds ratio, 1.40, [95% CI, 1.05-1.86]) and with ≥2 high-risk features (odds ratio, 3.94, [95% CI, 1.82-8.52]), although only 35 participants had this finding. Among participants with a coronary artery calcium score of 0 (n=1200), those with Lp(a) ≥125 nmol/L had a significantly higher percentage of any plaque compared with those with Lp(a) <125 nmol/L (24.2% versus 14.2%; P<0.001). CONCLUSIONS: In this contemporary analysis, elevated Lp(a) was independently associated with the presence of coronary plaque. Larger studies are needed to confirm the strong association observed with the presence of multiple high-risk coronary plaque features.

Association between a diagnosis of diabetes mellitus and smoking abstinence: An analysis of the National Health Interview Survey (2006-2018).

OBJECTIVE: Both diabetes and smoking significantly increase the risk of cardiovascular disease (CVD). Understanding whether a diagnosis of diabetes can be leveraged to promote smoking cessation is a gap in the literature. METHODS: We used data from the US National Health Interview Survey, 2006 to 2018, to investigate the relationship between self-report of diagnosis of diabetes and subsequent smoking abstinence among 142,884 respondents who reported regular smoking at baseline. Effect sizes were presented as hazard ratios (HRs) derived from multivariable Cox regression models adjusted for potential confounders using diabetes as a time-dependent covariate. Subgroup-specific estimates were obtained using interaction terms between diabetes and variables of interest. RESULTS: A self-reported diagnosis of diabetes was associated with smoking abstinence (HR: 1.21; 95% CI: 1.16 to 1.27). The strength of the association varied based on race (P for interaction: 0.004), where it was strongest in African Americans (HR: 1.44; 95% CI: 1.29 to 1.60); income (P for interaction <0.001), where it was strongest in those with a yearly income less than $35,000 (HR: 1.45; 95% CI: 1.36 to 1.53); and educational attainment (P for interaction <0.001), where it was strongest in those who did not attend college (HR: 1.48; 95% CI: 1.40 to 1.57). CONCLUSION: Among adults who smoke, a diagnosis of diabetes is significantly associated with subsequent smoking abstinence. The association is strongest in socially disadvantaged demographics, including African Americans, low-income individuals, and those who did not attend college.

Chest Symptoms and Long-Term Risk of Incident Cardiovascular Disease.

BACKGROUND: We sought to evaluate the associations of chest pain and dyspnea with the long-term risk of cardiovascular disease including coronary disease, heart failure, atrial fibrillation, and stroke. METHODS: In 13,200 participants without cardiovascular disease in the Atherosclerosis Risk in Communities study (1987-1989), chest pain was categorized into definite angina, possible angina, non-anginal chest pain, and no chest pain using the Rose questionnaire. Dyspnea was categorized into grades 3-4, 2, 1, and 0 by the modified Medical Research Council scale. The associations of chest pain and dyspnea with incident myocardial infarction, heart failure, atrial fibrillation, and stroke over a median follow-up of ∼27 years were quantified with multivariable Cox models. RESULTS: Definite angina and possible angina were associated with myocardial infarction (adjusted hazard ratios [HR] 1.80 [95%CI 1.45-2.13] and 1.65 [1.27-2.15]). Although lesser magnitude than myocardial infarction, both definite and possible angina were associated with heart failure. For atrial fibrillation, possible angina showed higher HR than definite angina. Dyspnea showed similar HRs for myocardial infarction and heart failure in grades 3-4 (2.00 [1.61-2.49] and 1.94 [1.62-2.32]). Stroke was least associated with chest symptoms. Chest pain and dyspnea significantly improved the discrimination of cardiovascular disease except stroke, beyond traditional risk factors. CONCLUSIONS: In individuals without cardiovascular disease, chest pain and dyspnea were independently associated with incident cardiovascular disease for about 3 decades, suggesting the need for evaluating chest pain from a broader perspective of cardiovascular disease beyond coronary disease and the importance of dyspnea for cardiovascular risk assessment including myocardial infarction.

Nontraditional Risk Markers for Incident Coronary Artery Calcium Among Persons ≥65 Years of Age.

Background: The initiation of coronary artery calcium (CAC) is an important physiologic milestone associated with increased cardiovascular disease risk. However, traditional risk factors (RF) do not perform well for predicting incident CAC among the 54 million older U.S. adults. Objectives: The authors sought to assess the association between nontraditional cardiovascular disease RF and incident CAC in older persons. Methods: There were 815 MESA (Multi-Ethnic Study of Atherosclerosis) participants ≥65 years of age who had CAC = 0 at Visit 1 and a follow-up CAC scan. Multivariable adjusted Cox hazards ratios (aHR) and C-statistics were calculated to examine the association of nontraditional RF with incident CAC. Results: The mean age was 70.2 years and 67% were women. The median follow-up time to repeat CAC scan was 3.6 years (IQR: 2.6-9.2 years) and 45% of participants developed incident CAC. Albuminuria (aHR: 1.50, 95% CI: 1.07-2.09), carotid plaque (aHR: 1.32, 95% CI: 1.04-1.66), and thoracic aortic calcification (TAC) (aHR: 1.38, 95% CI: 1.10-1.75) were significantly associated with incident CAC, while higher levels of nontraditional RF including apolipoprotein-B, lipoprotein(a), high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide were not. When added to demographics, albuminuria, carotid plaque, and TAC provided a greater C-statistic improvement (+0.047, P = 0.004) vs all traditional RF combined (+0.033, P = 0.05). Conclusions: Among nontraditional RF and measures of subclinical atherosclerosis, only albuminuria, carotid plaque, and TAC were significantly associated with incident CAC in persons ≥65 years of age. Identification of albuminuria or extracoronary atherosclerosis may help guide the timing of repeat CAC scoring in older persons with baseline CAC = 0.

Canadian Cost-Effectiveness of Coronary Artery Calcium Screening Based on the Multi-Ethnic Study of Atherosclerosis.

Background: Cost-effectiveness of testing for coronary artery calcium (CAC) relative to other treatment strategies is not established in Canada. Objectives: The purpose of this study was to evaluate the cost-effectiveness of using CAC score-guided statin treatment compared with universal statin therapy among intermediate-risk, primary prevention patients eligible for statins. Methods: A state transition, microsimulation model used data from Canadian sources and the Multi-Ethnic Study of Atherosclerosis to simulate clinical and economic consequences of cardiovascular disease from a Canadian publicly funded health care system perspective. In the CAC score-guided treatment arm, statins were started when CAC ≥1. Outcome of interest was the incremental cost-effectiveness ratio at 5 and 10 years; an incremental cost-effectiveness ratio <$50,000 per quality-adjusted life year (QALY) gained was considered cost-effective. Sensitivity analyses examined uncertainty in model parameters. Results: Compared with universal statin treatment at 5 and 10 years, CAC score-guided statin treatment was projected to increase mean costs by $326 (95% CI: $325-$326) and $172 (95% CI: $169-$175), increase mean QALYs by 0.01 (95% CI: 0.01-0.01) and 0.02 (95% CI: 0.02-0.02), and cost $54,492 (95% CI: $52,342-$56,816) and $8,118 (95% CI: $7,968-$8,279) per QALY gained, respectively. The model was most sensitive to statin cost, CAC testing cost, adherence to statin monitoring, and disutility associated with daily statin use. At 5 years, CAC score-guided statin treatment was cost-effective when CAC test costs ranged from $80 to $160 in different scenarios. Conclusions: CAC score-guided statin initiation in comparison to universal statin treatment was borderline cost-neutral at 5 years and cost-effective at 10 years in statin-eligible Canadian patients at intermediate cardiovascular disease risk.

The Association of Mitral Annular Calcification With Cardiovascular and Noncardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis.

Mitral annular calcification (MAC) may be a potential marker of biologic aging. However, the association of MAC with noncardiovascular measures, including bone mineral density (BMD), incident renal failure, dementia, and noncardiovascular mortality, is not well-studied in a multiracial cohort. We used data from 6,814 participants (mean age: 62.2 ± 10.2 years, 52.9% women) without cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC was assessed with noncontrast cardiac computed tomography at study baseline. Using multivariable-adjusted linear and logistic regression, we assessed the cross-sectional association of MAC with BMD and walking pace. Furthermore, using Cox proportional hazards, we evaluated the association of MAC with incident renal failure, dementia, and all-cause mortality. In addition, we assessed the association of MAC with cardiovascular and noncardiovascular mortality using competing risks regression. The prevalence of MAC was 9.5% and was higher in women (10.7%) than in men (8.0%). MAC was associated with low BMD (coefficient -0.04, 95% confidence interval [CI] -0.06 to -0.02), with significant interaction by gender (p-interaction = 0.035). MAC was, however, not associated with impaired walking pace (odds ratio 1.09, 95% CI 0.89 to 1.33). Compared with participants without MAC, those with MAC had an increased risk of incident renal failure, albeit nonsignificant (hazard ratio [HR] 1.18, 95% CI 0.95 to 1.45), and a significantly higher hazards of dementia (HR 1.36, 95% CI 1.10 to 1.70). In addition, participants with MAC had a substantially higher risk of all-cause (HR 1.47, 95% CI 1.29 to 1.69), cardiovascular (subdistribution HR 1.39, 95% CI 1.04 to 1.87), and noncardiovascular mortality (subdistribution HR 1.35, 95% CI 1.14 to 1.60) than those without MAC. MAC ≥100 versus <100 was significantly associated with reduced BMD, incident renal failure, dementia, all-cause, cardiovascular, and noncardiovascular mortality. In conclusion, MAC was associated with reduced BMD and dementia and all-cause, cardiovascular, and noncardiovascular mortality in this multiracial cohort. Thus, MAC may be a marker not only for atherosclerotic burden but also for other metabolic and inflammatory factors that increase the risk of noncardiovascular outcomes and death from other causes.

Association of Autoimmune Diseases With Coronary Atherosclerosis Severity and Ischemic Events.

BACKGROUND: Some autoimmune diseases carry elevated risk for atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanism and the influence of traditional risk factors remain unclear. OBJECTIVES: This study sought to determine whether autoimmune diseases independently correlate with coronary atherosclerosis and ASCVD risk and whether traditional cardiovascular risk factors modulate the risk. METHODS: The study included 85,512 patients from the Western Denmark Heart Registry undergoing coronary computed tomography angiography. A diagnosis of 1 of 18 autoimmune diseases was assessed. Adjusted OR (aOR) for any plaque, any coronary artery calcification (CAC), CAC of >90th percentile, and obstructive coronary artery disease as well as adjusted HR (aHR) for ASCVD were calculated. RESULTS: During 5.3 years (Q1-Q3: 2.8-8.2 years) of follow-up, 3,832 ASCVD events occurred. A total of 4,064 patients had a diagnosis of autoimmune disease, which was associated with both presence of any plaque (aOR: 1.29; 95% CI: 1.20-1.40), any CAC (aOR: 1.28; 95% CI: 1.19-1.37), and severe CAC of >90th percentile (aOR: 1.53; 95% CI: 1.39-1.68), but not with having obstructive coronary artery disease (aOR: 1.04; 95% CI: 0.91-1.17). Patients with autoimmune diseases had a 46% higher risk (aHR: 1.46; 95% CI: 1.29-1.65) for ASCVD. Traditional cardiovascular risk factors were strongly associated with future ASCVD events, and a favorable cardiovascular risk factor profile in autoimmune patients was associated with ∼54% lower risk compared to patients with presence of risk factors (aHR: 0.46; 95% CI: 0.27-0.81). CONCLUSIONS: Autoimmune diseases were independently associated with higher burden of coronary atherosclerosis and higher risk for future ASCVD events, with risk accentuated by traditional cardiovascular risk factors. These findings suggest that autoimmune diseases increase risk through accelerated atherogenesis and that cardiovascular risk factor control is key for improving prognosis in patients with autoimmune diseases.

Identifying People at High Risk for Severe Aortic Stenosis: Aortic Valve Calcium Versus Lipoprotein(a) and Low-Density Lipoprotein Cholesterol.

BACKGROUND: Aortic valve calcification (AVC), Lp(a) [lipoprotein(a)], and low-density lipoprotein cholesterol (LDL-C) are associated with severe aortic stenosis (AS). We aimed to determine which of these risk factors were most strongly associated with the risk of incident severe AS. METHODS: A total of 6792 participants from the MESA study (Multi-Ethnic Study of Atherosclerosis) had computed tomography-quantified AVC, Lp(a), and LDL-C values at MESA visit 1 (2000-2002). We calculated the absolute event rate of incident adjudicated severe AS per 1000 person-years and performed multivariable adjusted Cox proportional hazards regression. RESULTS: The mean age was 62 years old, and 47% were women. Over a median 16.7-year follow-up, the rate of incident severe AS increased exponentially with higher AVC, regardless of Lp(a) or LDL-C values. Participants with AVC=0 had a very low rate of severe AS even with elevated Lp(a) ≥50 mg/dL (<0.1/1000 person-years) or LDL-C ≥130 mg/dL (0.1/1000 person-years). AVC >0 was strongly associated with severe AS when Lp(a) <50 mg/dL hazard ratio (HR) of 33.8 (95% CI, 16.4-70.0) or ≥50 mg/dL HR of 61.5 (95% CI, 7.7-494.2) and when LDL-C <130 mg/dL HR of 31.1 (95% CI, 14.4-67.1) or ≥130 mg/dL HR of 50.2 (95% CI, 13.2-191.9). CONCLUSIONS: AVC better identifies people at high risk for severe AS compared with Lp(a) or LDL-C, and people with AVC=0 have a very low long-term rate of severe AS regardless of Lp(a) or LDL-C level. These results suggest AVC should be the preferred prognostic risk marker to identify patients at high risk for severe AS, which may help inform participant selection for future trials testing novel strategies to prevent severe AS.

Association of aortic valve calcium with dementia and stroke: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Calcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: AVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1-99, 100-299, ≥300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1000 person-years) and multivariable adjusted Cox proportional hazards ratios (HR). RESULTS: Overall, 6812 participants had AVC quantified with a mean age of 62.1 years old, 52.9 % were women, and the median 10-year estimated atherosclerotic cardiovascular disease (ASCVD) risk was 13.5 %. Participants with AVC >0 were older and less likely to be women compared to those with AVC=0. Over a median 16-year follow-up, there were 535 cases of dementia and 376 cases of stroke. The absolute risk of newly diagnosed dementia increased in a stepwise pattern with higher AVC scores, and stroke increased in a logarithmic pattern. In multivariable analyses, AVC was significantly associated with newly diagnosed dementia as a log-transformed continuous variable (HR 1.09; 95 % CI 1.04-1.14) and persons with AVC ≥300 had nearly a two-fold higher risk (HR 1.77; 95 % CI 1.14-2.76) compared to those with AVC=0. AVC was associated with an increased risk of stroke after adjustment for age, sex, and race/ethnicity, but not after adjustment for ASCVD risk factors. CONCLUSIONS: After multivariable adjustment, AVC >0 was significantly associated with an increased risk of newly diagnosed dementia, but not incident stroke. This suggests that AVC may be an important risk factor for the long-term risk of dementia beyond traditional ASCVD risk factors.

Overcoming barriers to implementation: Improving incidental coronary calcium reporting on non-EKG gated chest CT scans.

BACKGROUND: Current guidelines recommend the reporting of incidental coronary artery calcification (CAC) on non-electrocardigram-gated computed tomography (CT) scans of the chest. The finding of incidental moderate or severe CAC on non-cardiac non-contrast chest CT correlates with a CAC score ≥ 100 Agatston units, a guideline-based indication for a clinician-patient discussion regarding the initiation of statin therapy. In contemporary practice, whether the presence and severity of incidental CAC are routinely reported on such CT scans of the chest is unknown. METHODS: At a major university hospital, we collected a one-month convenience sample of 297 patients who had chest CT imaging for indications other than lung cancer screening (OICT) and 42 patients who underwent lung cancer chest CT screening (LSCT). We evaluated reporting patterns of incidental CAC in the body and impression of the reports as compared to the overreading of such studies by a board-certified CT chest radiologist. We hypothesized and demonstrated that there was underreporting of incidental CAC on these scans. We then undertook an initiative to educate reporting radiologists on the importance of reporting CAC and implemented a reporting template change to encourage routine reporting. Then we repeated another one-month sample (n= 363 for the OICT and n= 63 for the LSCT groups) to evaluate reporting patterns following our intervention. RESULTS: The presence of incidental moderate and severe CAC was systematically underreported in the OICT group (0 and 4.8 %) and the severity was never mentioned in the impression of reports. In the LSCT group, the presence of incidental moderate and severe CAC was also underreported (66.7 % and 75 %) and the severity of CAC was mentioned 50 % of the time in the impression of the reports. Following the initiation of an educational program and radiology reporting template change, there was a significant increase in reporting of moderate or severe CAC in the OICT group (0 vs. 80.0 %, p < 0.001) and (4.8 vs. 93.5 %, p < 0.001) respectively and a significant increase in the reporting of the severity of incidental CAC for those with severe CAC in the LSCT group (50 vs. 94.1 %, p=0.006). CONCLUSION: Despite guideline recommendations, incidental CAC was underreported at a large academic center. We implemented a system that significantly improved reporting patterns of incidental CAC. Failure to report incidental CAC represents a missed opportunity to initiate preventive therapies. Hospital systems interested in improving the quality of their radiology reporting procedures should examine their practices to assure that CAC quantification is routinely performed.

The association of carotid plaque burden and composition and the coronary artery calcium score in intermediate cardiovascular risk patients.

Both the carotid ultrasound and coronary artery calcium (CAC) score quantify subclinical atherosclerosis and are associated with cardiovascular disease and events. This study investigated the association between CAC score and carotid plaque quantity and composition. Adult participants (n = 43) without history of cardiovascular disease were recruited to undergo a carotid ultrasound. Maximum plaque height (MPH), total plaque area (TPA), carotid intima-media thickness (CIMT), and plaque score were measured. Grayscale pixel distribution analysis of ultrasound images determined plaque tissue composition. Participants then underwent CT to determine CAC score, which were also categorized as absent (0), mild (1-99), moderate (100-399), and severe (400+). Spearman correlation coefficients between carotid variables and CAC scores were computed. The mean age of participants was 63 ± 11 years. CIMT, TPA, MPH, and plaque score were significantly associated with CAC score (ρ = 0.60, p < 0.0001; ρ = 0.54, p = 0.0002; ρ = 0.38, p = 0.01; and ρ = 0.49, p = 0.001). Echogenic composition features %Calcium and %Fibrous tissue were not correlated to a clinically relevant extent. There was a significant difference in the TPA, MPH, and plaque scores of those with a severe CAC score category compared to lesser categories. While carotid plaque burden was associated with CAC score, plaque composition was not. Though CAC score reliably measures calcification, carotid ultrasound gives information on both plaque burden and composition. Carotid ultrasound with assessment of plaque features used in conjunction with traditional risk factors may be an alternative or additive to CAC scoring and could improve the prediction of cardiovascular events in the intermediate risk population.