Faculty Bibliography

OBJECTIVES:This study sought to evaluate the association and burden of coronary artery calcium (CAC) with long-term, cause-specific mortality across the spectrum of baseline risk. BACKGROUND:Although CAC is a known predictor of short-term, all-cause mortality, data on long-term and cause-specific mortality are inadequate. METHODS:The CAC Consortium cohort is a multicenter cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC testing. The following risk factors (RFs) were considered: 1) current cigarette smoking; 2) dyslipidemia; 3) diabetes mellitus; 4) hypertension; and 5) family history of CHD. RESULTS:During the 12.5-years median follow-up, 3,158 (4.7%) deaths occurred; 32% were cardiovascular disease (CVD) deaths. Participants with CAC scores ≥400 had a significantly increased risk for CHD and CVD mortality (hazard ratio [HR]: 5.44; 95% confidence interval [CI]: 3.88 to 7.62; and HR: 4.15; 95% CI: 3.29 to 5.22, respectively) compared with CAC of 0. Participants with ≥3 RFs had a smaller increased risk for CHD and CVD mortality (HR: 2.09; 95% CI: 1.52 to 2.85; and HR: 1.84; 95% CI: 1.46 to 2.31, respectively) compared with those without RFs. Across RF strata, CAC added prognostic information. For example, participants without RFs but with CAC ≥400 had significantly higher all-cause, non-CVD, CVD, and CHD mortality rates compared with participants with ≥3 RFs and CAC of 0. CONCLUSIONS:Across the spectrum of RF burden, a higher CAC score was strongly associated with long-term, all-cause mortality and a greater proportion of deaths due to CVD and CHD. Absence of CAC identified people with a low risk over 12 years of follow-up, with most deaths being non-CVD in nature, regardless of RF burden.

Background Coronary artery calcium (CAC) is a predictor for the development of cardiovascular disease (CVD) and to a lesser extent cancer. The age- and sex-specific relationship of CAC with CVD and cancer mortality is unknown. Methods and Results Asymptomatic patients aged 40 to 75 years old without known CVD were included from the CAC Consortium. We calculated sex-specific mortality rates per 1000 person-years' follow-up. Using parametric survival regression modeling, we determined the age- and sex-specific CAC score at which the risk of death from CVD and cancer were equal. Among the 59 502 patients included in this analysis, the mean age was 54.9 (±8.5) years, 34% were women, and 89% were white. There were 671 deaths attributable to CVD and 954 deaths attributable to cancer over a mean follow-up of 12±3 years. Among patients with CAC=0, cancer was the leading cause of death, the total mortality rate was low (women, 1.8; men, 1.5), and the CVD mortality rate was exceedingly low for women (0.3) and men (0.3). The age-specific CAC score at which the risk of CVD and cancer mortality were equal had a U-shaped relationship for women, while the relationship was exponential for men. Conclusions The age- and sex-specific relationship of CAC with CVD and cancer mortality differed significantly for women and men. Our age- and sex-specific CAC score provides a more precise estimate and further facilitates the use of CAC as a synergistic tool in strategies for the prediction and prevention of CVD and cancer mortality.

The 2013 American College of Cardiology and the American Heart Association (ACC/AHA) guidelines resulted in broad recommendations for preventive statin therapy allocation in patients without known cardiovascular disease (CVD). Subsequent studies demonstrated significant heterogeneity of atherosclerotic cardiovascular disease risk across the primary prevention population. In 2018/2019, the guidelines were revised to optimize risk assessment and cholesterol management. We sought to evaluate the heterogeneity of risk in statin-recommended patients, using coronary artery calcium (CAC) according to 2018/2019 ACC/AHA guidelines in a primary prevention cohort. We evaluated 5,800 statin-naive patients aged 40 to 75 years without known coronary heart disease from the Cedars-Sinai Medical Center study cohort. All participants underwent clinical CAC scoring for risk stratification and were followed for all-cause and CVD-specific mortality. A total of 181 deaths occurred including 54 CVD deaths over a follow-up of 9.5 years. Overall, 1,939 participants would have been recommended statin therapy, 32% of whom had no detectable CAC. CAC = 0 participants had the lowest all-cause and CVD mortality rates in both statin-recommended and nonrecommended groups (0.2 and 0.4 CVD deaths per 1,000 person-years, respectively). Absence of CAC in statin-naive patients portends an approximately 12-fold lower CVD mortality (0.2% vs 2.4%) in those recommended for statin therapy compared with any CAC present. In conclusion, in a cohort of patients meeting the 2018/2019 ACC/AHA guidelines for statin therapy for primary prevention, there was a marked heterogeneity of CAC scores, with about one-third of the statin recommended population having no detectable CAC (CAC = 0) with a significantly lower CVD mortality compared with CAC>0.

BACKGROUND AND AIMS:We sought to understand the risk factor correlates of very early coronary artery calcium (CAC), and the potential investigational value of CAC phenotyping in adults aged 20-30 years. METHODS:We studied all participants aged 20-30 years at baseline (N = 373) in the Coronary Artery Calcium Consortium, a large multi-center cohort study of patients aged 18 years or older without known atherosclerotic cardiovascular disease (ASCVD) at baseline, referred for CAC scoring for clinical risk stratification. We described the prevalence of CAC in men and women, the frequency of risk factors by the presence of CAC (CAC = 0 vs CAC >0), and assessed the association between traditional non-demographic CVD risk factors (hypertension, hyperlipidemia, smoking, family history of CHD, and diabetes) and prevalent CAC, using age- and sex-adjusted logistic regression models. RESULTS:The mean age of the study participants was 27.5 ± 2.4 years; 324 (86.9%) had CAC = 0, and 49 (13.1%) had CAC >0. Among the 49 participants with CAC, 38 (77.6%) were men, and median CAC score was low at 4.6. In age- and sex-adjusted models, there was a graded increase in the odds of CAC >0 with increasing traditional cardiovascular disease (CVD) risk factor burden (p = 0.001 for linear trend). Participants with ≥3 traditional risk factors had a statistically significant higher odds of having prevalent CAC (OR 5.57, 95% CI; 1.82-17.03) compared to participants with no risk factors. CONCLUSIONS:Our study demonstrates the non-negligible prevalence of CAC among very high-risk young US adults, reinforcing the critical importance of traditional risk factors in the earliest development of detectable subclinical ASCVD.

BACKGROUND:Coronary artery calcium (CAC) is a guideline recommended cardiovascular disease (CVD) risk stratification tool that increases with age and is associated with non-cardiovascular disease outcomes including cancer. We sought to define the age-specific change in the association between CAC and cause-specific mortality. METHODS:The Coronary Artery Calcium Consortium includes 59,502 asymptomatic patients age 40-75 without known CVD. Age-stratified mortality rates and parametric survival regression modeling was performed to estimate the age-specific CAC score at which CVD and cancer mortality risk were equal. RESULTS:The mean age was 54±8 years (67% men) and there were 2,423 deaths over a mean 12±3 years follow-up. Among individuals with CAC = 0, cancer was the leading cause of death, with low CVD mortality rates for both younger (40-54 years) 0.2/1,000 person-years and older participants (65-75 years) 1.3/1,000 person-years. When CAC ≥400, CVD was consistently the leading cause of death among younger (71% of deaths) and older participants (56% of deaths). The CAC score at which CVD overtook cancer as the leading cause of death increased exponentially with age and was approximately 115 at age 50 and 380 at age 65. CONCLUSIONS:Regardless of age, when CAC = 0 cancer was the leading cause of death and the cardiovascular disease mortality rate was low. Our age-specific estimate for the CAC score at which CVD overtakes cancer mortality allows for a more precise approach to synergistic prediction and prevention strategies for CVD and cancer.

BACKGROUND AND AIMS:Cardiovascular disease (CVD) and cancer are the two leading causes of death in smokers. Lung cancer screening is recommended in a large proportion of smokers. We examined the implication of coronary artery calcium (CAC) score (quantitative and qualitative) for cardiovascular disease (CVD), coronary heart disease (CHD), and cancer mortality risk prediction among current smokers. METHODS:We included current smokers without known heart disease from the CAC Consortium. Cox regression (for all-cause mortality) and Fine-and-Gray competing-risk regression (for CVD, CHD, and cancer mortality) models, adjusted for traditional CVD risk factors, were used to assess the association between CAC and each mortality outcome, with CAC as a continuous (log2-transformed) or categorical variable (CAC = 0, CAC = 1-99, CAC = 100-399, and CAC ≥400). We used number of vessels with CAC as a surrogate for the qualitative measure of CAC and mortality outcomes. Analyses were repeated for lung cancer screening-eligible population (defined as ever smokers with >30 pack years smoking history) (n = 1,149). Hazard ratios (HR) for all-cause mortality and Subdistribution HRs (sHR) with 95% confidence intervals (CI) were reported. RESULTS:Over a median of 11.9 years (25th-75th percentile: 10.2-13.3) of follow-up, of 5,147 current smokers (mean age 52.5 ± 9.4, 32.4% women) 337 died (102 of CVD, 54 of CHD, and 123 of cancer). A doubling of CAC score was associated with increased HRs of all-cause mortality (1.10 (1.06-1.14)), and sHRs for CVD (1.15 (1.07-1.24)), CHD (1.26 (1.11-1.42)) and cancer mortality (1.06 (1.00-1.13)). Those with CAC ≥400 had increased sHR of CVD (3.55 (1.70-7.41)), CHD (8.80 (2.41-32.10)), and cancer mortality (1.85 (1.07-3.22)), compared with those with CAC = 0. A diffuse CAC pattern significantly increased the risk of all-cause, CVD, and CHD mortality among smokers. Results were consistent for the lung cancer screening-eligible population. CONCLUSIONS:Qualitative and quantitative CAC scores can prognosticate risk of all-cause, CVD, CHD, and cancer mortality beyond traditional risk factors among all smokers as well as those eligible for lung cancer screening.

This case reports a 47-year-old male with a history of IV drug abuse, presenting with one week of left lower back pain. During the initial treatment, the patient became hemodynamically unstable, requiring vasopressor support. Transthoracic echocardiography (TTE) revealed a 1 cm x 1 cm aortic valve vegetation with severe aortic regurgitation and potential perforation of the valve leaflet. After hemodynamic stability was achieved, the patient left against medical advice, refusing urgent valvular surgery. Subsequent follow-up unveiled repeated recurrence of symptoms and surgical repair of the aortic valve.

Routinely used automated immunoassays have been found to give unrealiable measurements of thyroid hormones in the presence of either high or low levels of thyroxine-binding globulin. Thyroid hormones are not the only analytes bound to specific binding proteins that are measured by immunoassays. Preliminary data from a series of cases, comparing IA measurements to those obtained by liquid chromatography-tandem mass spectrometry, reveal for the first time that IA measurements report falsely low (by an average of 27%) serum cortisol concentrations. Initial findings suggest that IA measurements of serum cortisol are affected by high concentrations of corticosteroid binding globulin.

OBJECTIVE:To test the hypothesis that markers of coagulation and hemostatic activation (MOCHA) help identify causes of cryptogenic stroke, we obtained serum measurements on 132 patients and followed them up to identify causes of stroke. METHODS:Consecutive patients with cryptogenic stroke who met embolic stroke of undetermined source (ESUS) criteria from January 1, 2017, to October 31, 2018, underwent outpatient cardiac monitoring and the MOCHA profile (serum D-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) obtained ≥2 weeks after the index stroke; abnormal MOCHA profile was defined as ≥2 elevated markers. Prespecified endpoints monitored during routine clinical visits included new atrial fibrillation (AF), malignancy, venous thromboembolism (VTE), or other defined hypercoagulable states (HS). RESULTS:= 0.79). The combination of 4 normal MOCHA and normal left atrial size (n = 30) had 100% sensitivity for ruling out the prespecified endpoints. CONCLUSION:The MOCHA profile identified patients with cryptogenic stroke more likely to have new malignancy, VTE, or HS during short-term follow-up and may be useful in direct evaluation for underlying causes of cryptogenic stroke.