Assessment of lifestyle "vital signs" in healthcare settings.

Unhealthy lifestyles, such as maintenance of poor diets and physical inactivity, are a powerful driver of disease-producing risk factors and chronic illnesses. This has led to an increasing call to assess adverse lifestyle factors in healthcare settings. This approach could be aided by designating health-related lifestyle factors as "vital signs" that can be recorded during patient visits. Just such an approach has been used for assessing patients' smoking habits since the 1990s. In this review, we assess the rationale for addressing six other health-related lifestyle factors, beyond smoking, in patient care settings: physical activity (PA), sedentary behavior (SB), participation in muscle strengthening exercises, mobility limitations, diet, and sleep quality. For each domain, we evaluate the evidence that supports currently proposed ultra-short screening tools. Our analysis indicates strong medical evidence to support the use of one to two-item screening questions for assessing patients' PA, SB, muscle strengthening activities, and presence of "pre-clinical" mobility limitations. We also present a theoretical basis for measuring patients' diet quality through use of an ultrashort dietary screen, based on evaluation of healthy food intake (fruits/vegetables) and unhealthy food intake (high consumption of highly processed meats and/or consumption of sugary foods and beverages) and a proposed evaluation of sleep quality using a single-item screener. The result is a 10-item lifestyle questionnaire that is based on patient self-report. As such, this questionnaire has the potential to be employed as a practical tool for assessing health behaviors in clinical care settings without impairing the normal workflow of healthcare providers.

Association between hypercholesterolemia and mortality risk among patients referred for cardiac imaging test: Evidence of a "cholesterol paradox?"

AIM: Some observational studies have observed a lower, rather than higher, mortality rate in association with hypercholesterolemia during follow-up of patients after cardiac stress testing. We aim to assess the relationship of hypercholesterolemia and other CAD risk factors to mortality across a wide spectrum of patients referred for various cardiac tests. METHODS AND RESULTS: We identified four cardiac cohorts: 64,357 patients undergoing coronary artery calcium (CAC) scanning, 10,814 patients undergoing coronary CT angiography (CCTA), 31,411 patients without known CAD undergoing stress/rest single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and 5051 patients with known CAD undergoing stress/rest SPECT-MPI. Each cohort was followed for all-cause mortality using risk-adjusted Cox models. We pooled the hazard ratios between cohorts with a random effects model. Baseline risk varied markedly among cohorts, from an annualized mortality rate of 0.31%/year in CAC patients to 3.63%/year among SPECT-MPI patients with known CAD. Hypertension, diabetes, and smoking were each associated with increased mortality in each patient cohort (pooled hazard ratio[95% CI]: 1.38[1.33-1.44], 1.88[1.76-2.00], and 1.67[1.48-1.86], respectively). By contrast, hypercholesterolemia was associated with decreased rather than increased mortality (pooled hazard ratio[95% CI]: 0.71[0.58-0.84]). Analysis of serum lipids among 7744 patients undergoing CAC or CCTA scanning revealed an inverse relationship between LDL cholesterol and mortality. CONCLUSIONS: Among a broad spectrum of patients referred for a variety of cardiac tests and ranging from low to high clinical risk, hypercholesterolemia was not associated with increased mortality risk. Our findings suggest that hypercholesterolemia may be sensitive to confounding by other clinical factors and post-test treatment changes in patient populations.

Coronary artery calcium is associated with long-term mortality from lung cancer: Results from the Coronary Artery Calcium Consortium.

BACKGROUND AND AIMS: Coronary artery calcium (CAC) scores have been shown to be associated with CVD and cancer mortality. The use of CAC scores for overall and lung cancer mortality risk prediction for patients in the Coronary Artery Calcium Consortium was analyzed. METHODS: We included 55,943 patients aged 44-84 years without known heart disease from the CAC Consortium. There were 1,088 cancer deaths, among which 231 were lung cancer, identified by death certificates with a mean follow-up of 12.2 ± 3.9 years. Fine-and-Gray competing-risk regression was used for overall and lung cancer-specific mortality, accounting for the competing risk of CVD death and after adjustment for CVD risk factors. Subdistribution hazard ratios (SHR) were reported. RESULTS: The mean age of all patients was 57.1 ± 8.6 years, 34.9% were women, and 89.6% were white. Overall, CAC was strongly associated with cancer mortality. Lung cancer mortality increased with increasing CAC scores, with rates per 1000-person years of 0.2 (95% CI: 0.1-0.3) for CAC = 0 and 0.8 (95% CI: 0.6-1.0) for CAC ≥400. Compared with CAC = 0, hazards were increased for those with CAC ≥400 for lung cancer mortality [SHR: 1.7 (95% CI: 1.2-2.6)], which was driven by women [SHR: 2.3 (95% CI: 1.1-4.8)], but not significantly increased for men. Risks were higher in those with positive smoking history [SHR: 2.2 (95% CI: 1.2-4.2)], with associations driven by women [SHR: 4.0 (95% CI: 1.4-11.5)]. CONCLUSIONS: CAC scores were associated with increased risks for lung cancer mortality, with strongest associations for current and former smokers, especially in women. Used in conjunction with other clinical variables, our data pinpoint a potential synergistic use of CAC scanning beyond CVD risk assessment for identification of high-risk lung cancer screening candidates.

Modeling the Recommended Age for Initiating Coronary Artery Calcium Testing Among At-Risk Young Adults.

BACKGROUND: There are currently no recommendations guiding when best to perform coronary artery calcium (CAC) scanning among young adults to identify those susceptible for developing premature atherosclerosis. OBJECTIVES: The purpose of this study was to determine the ideal age at which a first CAC scan has the highest utility according to atherosclerotic cardiovascular disease (ASCVD) risk factor profile. METHODS: We included 22,346 CAC Consortium participants aged 30-50 years who underwent noncontrast computed tomography. Sex-specific equations were derived from multivariable logistic modeling to estimate the expected probability of CAC >0 according to age and the presence of ASCVD risk factors. RESULTS: Participants were on average 43.5 years of age, 25% were women, and 34% had CAC >0, in whom the median CAC score was 20. Compared with individuals without risk factors, those with diabetes developed CAC 6.4 years earlier on average, whereas smoking, hypertension, dyslipidemia, and a family history of coronary heart disease were individually associated with developing CAC 3.3-4.3 years earlier. Using a testing yield of 25% for detecting CAC >0, the optimal age for a potential first scan would be at 36.8 years (95% CI: 35.5-38.4 years) in men and 50.3 years (95% CI: 48.7-52.1 years) in women with diabetes, and 42.3 years (95% CI: 41.0-43.9 years) in men and 57.6 years (95% CI: 56.0-59.5 years) in women without risk factors. CONCLUSIONS: Our derived risk equations among health-seeking young adults enriched in ASCVD risk factors inform the expected prevalence of CAC >0 and can be used to determine an appropriate age to initiate clinical CAC testing to identify individuals most susceptible for early/premature atherosclerosis.

Feasibility of Using an Ultrashort Lifestyle Questionnaire to Predict Future Mortality Risk among Patients with Suspected Heart Disease.

Adverse health behaviors are potent drivers of chronic disease and premature mortality. This has led to the development of various lifestyle scores to predict clinical risk, but their complexity makes them impractical for use in clinical settings. Thus, there is a need to develop a brief lifestyle score that can assess factors such as exercise and diet within the constraints of routine medical practice. Accordingly, we assessed 19,081 patients undergoing coronary artery calcium (CAC) scanning between September 1, 1998 and December 30, 2016. Each patient completed a questionnaire that included a two-item lifestyle scale regarding patients' frequency of exercise and adherence to a low saturated fat diet. Patients' responses were used to generate a lifestyle score which ranged from very low risk to high risk. Patients were followed for a median of 11.0 years for all-cause mortality. A stepwise relationship was noted between worse lifestyle scores and increased frequency of hypertension, diabetes, smoking, obesity, waist/hip ratio, and resting heart rate and blood pressure. Among patients with zero CAC scores, mortality risk was low regardless of lifestyle score, but as CAC abnormality increased, a stepwise relationship emerged between worse lifestyle scores and mortality. The lifestyle score was more predictive of mortality than conventional CAD risk factors according to multivariable Chi-square analysis. Thus, our results establish the practicality of an ultrashort lifestyle questionnaire that could be employed in nearly all clinical settings. Within our study, our two-item lifestyle scale showed a stepwise relationship to known CAD risk factors and predicted future mortality.

Thoracic Aortic Calcium for the Prediction of Stroke Mortality (from the Coronary Artery Calcium Consortium).

Thoracic aortic calcium(TAC) is an important marker of extracoronary atherosclerosis with established predictive value for all-cause mortality. We sought to explore the predictive value of TAC for stroke mortality, independent of the more established coronary artery calcium (CAC) score. The CAC Consortium is a retrospectively assembled database of 66,636 patients aged ≥18 years with no previous history of cardiovascular disease, baseline CAC scans for risk stratification, and follow-up for 12 ± 4 years. CAC scans capture the adjacent thoracic aorta, enabling assessment of TAC from the same images. TAC was available in 41,066 (62%), and was primarily analyzed as present or not present. To account for competing risks for nonstroke death, we utilized multivariable-adjusted Fine and Gray competing risk regression models adjusted for traditional cardiovascular risk factors and CAC score. The mean age of participants was 53.8 ± 10.3 years, with 34.4% female. There were 110 stroke deaths during follow-up. The unadjusted subdistribution hazard ratio (SHR) for stroke mortality in those who had TAC present compared with those who did not was 8.80 (95% confidence interval [CI]: 5.97, 12.98). After adjusting for traditional risk factors and CAC score, the SHR was 2.21 (95% CI:1.39,3.49). In sex-stratified analyses, the fully adjusted SHR for females was 3.42 (95% CI: 1.74, 6.73) while for males it was 1.55 (95% CI: 0.83, 2.90). TAC was associated with stroke mortality independent of CAC and traditional risk factors, more so in women. The presence of TAC appears to be an independent risk marker for stroke mortality.

Relation of Intake of Saturated Fat to Atherosclerotic Risk Factors, Health Behaviors, Coronary Atherosclerosis, and All-Cause Mortality Among Patients Who Underwent Coronary Artery Calcium Scanning.

Although very brief questionnaires are commonly used to assess physical activity, an analogous approach for assessing diet quality within clinical practice has not been developed. Thus, we undertook an exploratory study to evaluate the association between a single-item questionnaire regarding dietary quality and patient risk profiles, lifestyle habits, lipid values, coronary artery calcium (CAC) scores and mortality. We assessed 15,368 patients who underwent CAC scanning, followed for a median of 12.1 years for all-cause mortality. Diet quality was assessed according to a single-item question regarding self-reported adherence to a low saturated fat diet (0 = never, 10 = always), with patients categorized into 4 dietary groups based on their response, ranging from low to very high saturated fat intake. We observed a significant stepwise association between reported saturated fat intake and smoking, exercise activity, obesity, and serum cholesterol, low density lipoprotein, and triglyceride values. Following adjustment for age and risk factors, patients reporting very high saturated fat intake had an elevated hazard ratio for mortality versus low saturated fat intake: 1.22 (95% confidence interval 1.04 to 1.44). The hazard ratio was no longer significant after further adjustment for exercise activity. Upon division of patients according to baseline CAC, a stepwise relationship was noted between increasing saturated fat intake and mortality among patients with CAC scores ≥400 (p = 0.002). Thus, within our cohort, just a single-item exploratory questionnaire regarding very high saturated fat intake revealed stepwise associations with health behaviors and cardiac risk factors, suggesting the basis for further development of a practical dietary questionnaire for clinical purposes.

Percutaneous or surgical revascularization is associated with survival benefit in stable coronary artery disease.

AIMS: We assessed the association between early invasive therapy, burden of ischaemia, and survival benefit separately for percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Ischaemia involving more than 10% of the left ventricular myocardium may identify patients who benefit from revascularization. However, it is not clear whether this association exists with both PCI and CABG. MATERIALS AND RESULTS: Patients who underwent single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) between 1992 and 2012 were identified. Early revascularization was defined as PCI or CABG performed within 90 days of SPECT MPI. The association between early PCI or CABG and all-cause mortality was assessed using a doubly robust, propensity score matching analysis. In total, 54 522 patients were identified, with median follow-up 8.0 years. Early PCI was performed in 2688 patients and early CABG in 1228. In the matched cohorts, early revascularization was associated with improved survival compared to medical therapy in patients with more than 15% ischaemia for both PCI [adjusted hazard ratio (HR) 0.70, P = 0.002] and CABG (adjusted HR 0.73, P = 0.008). CONCLUSION: In this observational analysis, both PCI and CABG were associated with reduced all-cause mortality in the presence of moderate to severe ischaemia after adjusting for factors leading to revascularization. As the threshold for improved outcomes with revascularization was similar for PCI and CABG, our results suggest that decisions for PCI vs. CABG for early revascularization should be determined by coronary anatomy, patient characteristics, and shared decision making, but not by the burden of ischaemia.

Predictors of coronary artery calcium among 20-30-year-olds: The Coronary Artery Calcium Consortium.

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.

Coronary Artery Calcium and the Age-Specific Competing Risk of Cardiovascular Versus Cancer Mortality: The Coronary Artery Calcium Consortium.

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.

Coronary Artery Calcium as a Synergistic Tool for the Age- and Sex-Specific Risk of Cardiovascular and Cancer Mortality: The Coronary Artery Calcium Consortium.

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 association of coronary artery calcium score and mortality risk among smokers: The coronary artery calcium consortium.

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.

Association between coronary artery calcium and cardiovascular disease as a supporting cause in cancer: The CAC consortium.

BACKGROUND: Identifying cancer patients at high risk of CVD is important for targeting CVD prevention strategies and evaluating chemotherapy options in the context of cardiotoxicity. Coronary artery calcium (CAC), a strong marker of coronary atherosclerosis, is used clinically to enhance risk assessment, yet the value of CAC for assessing risk of CVD complications in cancer is poorly understood. OBJECTIVE: In cases of cancer mortality, to determine the value of CAC for predicting risk of CVD as a supporting cause of death. METHODS: The CAC Consortium is a multi-center cohort of 66,636 asymptomatic adults without CVD who underwent CAC scanning. During a follow-up of 12.5 years, 1129 patients died of cancer and were included in this analysis. The primary outcome was presence of CVD listed as a supporting cause of cancer mortality on official death certificates obtained from the National Death Index. Logistic regression models were used to assess the odds of CVD being listed as a supporting cause of death by CAC. RESULTS: CVD was listed as a supporting cause of death in 306 (27%) cancer mortality cases. Baseline CAC was significantly higher in individuals with CVD-supported mortality. Odds ratios of having CVD-supported death increased by ASCVD risk score category [1.15 (0.81, 1.65) for 5-20% 10-year risk and 1.97 (1.36, 2.89) for ≥20% risk, in reference to <5% 10-year ASCVD risk] and CAC category [1.07 (0.73, 1.57) for CAC 1-99, 1.29 (0.87, 1.93) for CAC 100-399, and 2.14 (1.48, 3.09) for CAC ≥400 relative to CAC 0]. In the CAC ≥400 group, these associations remained significantly elevated after adjustment for traditional CVD risk factors [1.66 (1.08, 2.55)]. A sensitivity analysis using a more specific ASCVD-supported mortality outcome, defined as coronary heart disease, stroke, and peripheral artery disease, demonstrated that adjusted odds of ASCVD-supported cancer mortality were significantly elevated in the CAC ≥400 group relative to CAC 0 [3.09 (1.39, 7.38)]. CONCLUSIONS: In cancer mortality cases, high antecedent CAC predicted risk of having CVD as a supporting cause of death on official death certificates, independently of ASCVD risk score and CVD risk factors. CAC may be useful for identifying cancer patients at high CVD risk who might benefit from more intense preventive cardiovascular therapies.

Long-Term All-Cause and Cause-Specific Mortality in Asymptomatic Patients With CAC ≥1,000: Results From the CAC Consortium.

OBJECTIVES: This study thoroughly explored the demographic and imaging characteristics, as well as the all-cause and cause-specific mortality risks of patients with a coronary artery calcium (CAC) score ≥1,000 in the largest dataset of this population to date. BACKGROUND: CAC is commonly used to quantify cardiovascular risk. Current guidelines classify a CAC score of >300 or 400 as the highest risk group, yet little is known about the potentially unique imaging characteristics and mortality risk in individuals with a CAC score ≥1,000. METHODS: A total of 66,636 asymptomatic adults were included from the CAC consortium, a large retrospective multicenter clinical cohort. Mean patient follow-up was 12.3 ± 3.9 years for patients with cardiovascular disease (CVD), coronary heart disease (CHD), cancer, and all-cause mortality. Multivariate Cox proportional hazards regression models adjusted for age, sex, and conventional risk factors were used to assess the relative mortality hazard of individuals with CAC ≥1,000 compared with, first, a CAC reference of 0, and second, with patients with a CAC score of 400 to 999. RESULTS: There were 2,869 patients with CAC ≥1,000 (86.3% male, mean 66.3 ± 9.7 years of age). Most patients with CAC ≥1,000 had 4-vessel CAC (mean: 3.5 ± 0.6 vessels) and had greater total CAC area, higher mean CAC density, and more extracoronary calcium (79% with thoracic artery calcium, 46% with aortic valve calcium, and 21% with mitral valve calcium) than those with CAC scores of 400 to 999. After full adjustment, those with CAC ≥1,000 had a 5.04- (95% confidence interval [CI]: 3.92 to 6.48), 6.79- (95% CI: 4.74 to 9.73), 1.55- (95% CI:1.23 to 1.95), and 2.89-fold (95% CI: 2.53 to 3.31) risk of CVD, CHD, cancer, and all-cause mortality, respectively, compared to those with CAC score of 0. The CAC ≥1,000 group had a 1.71- (95% CI: 1.41 to 2.08), 1.84- (95% CI: 1.43 to 2.36), 1.36- (95% CI:1.07 to 1.73), and 1.51-fold (95% CI: 1.33 to 1.70) increased risk of CVD, CHD, cancer, and all-cause mortality compared to those with CAC scores 400 to 999. Graphic analysis of CAC ≥1,000 patients revealed continued logarithmic increase in risk, with no clear evidence of a risk plateau. CONCLUSIONS: Patients with extensive CAC (CAC ≥1,000) represent a unique very high-risk phenotype with mortality outcomes commensurate with high-risk secondary prevention patients. Future guidelines should consider CAC ≥1,000 patients to be a distinct risk group who may benefit from the most aggressive preventive therapy.

All-cause and cause-specific mortality in individuals with zero and minimal coronary artery calcium: A long-term, competing risk analysis in the Coronary Artery Calcium Consortium.

BACKGROUND AND AIMS: The long-term associations between zero, minimal coronary artery calcium (CAC) and cause-specific mortality are currently unknown, particularly after accounting for competing risks with other causes of death. METHODS: We evaluated 66,363 individuals from the CAC Consortium (mean age 54 years, 33% women), a multi-center, retrospective cohort study of asymptomatic individuals undergoing CAC scoring for clinical risk assessment. Baseline evaluations occurred between 1991 and 2010. RESULTS: Over a mean of 12 years of follow-up, individuals with CAC = 0 (45% prevalence, mean age 45 years) had stable low rates of coronary heart disease (CHD) death, cardiovascular disease (CVD) death (ranging 0.32 to 0.43 per 1000 person-years), and all-cause death (1.38-1.62 per 1000 person-years). Cancer was the predominant cause of death in this group, yet rates were also very low (0.47-0.79 per 1000 person-years). Compared to CAC = 0, individuals with CAC 1-10 had an increased multivariable-adjusted risk of CVD death only under age 40. Individuals with CAC>10 had multivariable-adjusted increased risks of CHD death, CVD death and all-cause death at all ages, and a higher proportion of CVD deaths. CONCLUSIONS: CAC = 0 is a frequent finding among individuals undergoing CAC scanning for risk assessment and is associated with low rates of all-cause death at 12 years of follow-up. Our results support the emerging consensus that CAC = 0 represents a unique population with favorable all-cause prognosis who may be considered for more flexible treatment goals in primary prevention. Detection of any CAC in young adults could be used to trigger aggressive preventive interventions.

Association of Coronary Artery Calcium With Long-term, Cause-Specific Mortality Among Young Adults.

Importance: The level of coronary artery calcium (CAC) can effectively stratify cardiovascular risk in middle-aged and older adults, but its utility for young adults is unclear. Objectives: To determine the prevalence of CAC in adults aged 30 to 49 years and the subsequent association of CAC with coronary heart disease (CHD), cardiovascular disease (CVD), and all-cause mortality. Design, Setting, and Participants: A multicenter retrospective cohort study was conducted among 22 346 individuals from the CAC Consortium who underwent CAC testing (baseline examination, 1991-2010, with follow-up through June 30, 2014; CAC quantified using nonconrast, cardiac-gated computed tomography scans) for clinical indications and were followed up for cause-specific mortality. Participants were free of clinical CVD at baseline. Statistical analysis was performed from June 1, 2017, to May 31, 2018. Main Outcomes and Measures: The prevalence of CAC and the subsequent rates of CHD, CVD, and all-cause mortality. Competing risks regression modeling was used to calculate multivariable-adjusted subdistribution hazard ratios for CHD and CVD mortality. Results: The sample of 22 346 participants (25.0% women and 75.0% men; mean [SD] age, 43.5 [4.5] years) had a high prevalence of hyperlipidemia (49.6%) and family history of CHD (49.3%) but a low prevalence of current smoking (11.0%) and diabetes (3.9%). The prevalence of any CAC was 34.4%, with 7.2% having a CAC score of more than 100. During follow-up (mean [SD], 12.7 [4.0] years), there were 40 deaths related to CHD, 84 deaths related to CVD, and 298 total deaths. A total of 27 deaths related to CHD (67.5%) occurred among individuals with CAC at baseline. The CHD mortality rate per 1000 person-years was 10-fold higher among those with a CAC score of more than 100 (0.69; 95% CI, 0.41-1.16) compared with those with a CAC score of 0 (0.07; 95% CI, 0.04-0.12). After multivariable adjustment, those with a CAC score of more than 100 had a significantly increased risk of CHD (subdistribution hazard ratio, 5.6; 95% CI, 2.5-12.7), CVD (subdistribution hazard ratio, 3.3; 95% CI, 1.8-6.2), and all-cause mortality (hazard ratio, 2.6; 95% CI, 1.9-3.6) compared with those with a CAC score of 0. Conclusions and Relevance: In a large sample of young adults undergoing CAC testing for clinical indications, 34.4% had CAC, and those with elevated CAC scores had significantly higher rates of CHD and CVD mortality. Coronary artery calcium may have potential utility for clinical decision-making among select young adults at elevated risk of cardiovascular disease.

Utility of novel serum biomarkers to predict subclinical atherosclerosis: A sub-analysis of the EISNER study.

BACKGROUND AND AIMS: Certain novel biomarkers may predict atherosclerotic cardiovascular disease (ASCVD) events; however, data on their relationship to coronary atherosclerosis and its progression as measured by coronary artery calcium (CAC) scanning is lacking. We evaluated the association between novel biomarkers and presence or progression of CAC. METHODS: The EISNER study was a prospective trial of patients without known ASCVD. Data on CAC and several biomarkers (hs-CRP, LTßR, osteopontin [OPN], RAGE, TNFR1α and TROY) were available at baseline and 4-year follow-up. Biomarkers were standardized and summed for a composite score. CAC progression was defined by the square-root (CACSQRT) method and rapid (top decile) progression. Adjusted regression models created a final prediction model for baseline CAC and CAC progression. RESULTS: 1207 subjects (mean age 58.4 ±â€¯8 years, 53% male) were evaluated; 621 had a baseline CAC >0, in whom 323 progressed by CACSQRT, and 121 rapidly progressed. Baseline CAC was associated only with OPN (p = 0.03), TROY (p = 0.0058) and TNFR1α (p = 0.0039) in unadjusted analyses. In adjusted analyses, only OPN was independently related to CAC progression using CACSQRT (p = 0.04). CONCLUSIONS: OPN identifies progression of atherosclerosis in persons free of ASCVD at baseline and may be a useful predictive tool to guide ASCVD prevention management.

Extensive thoracic aortic calcification is an independent predictor of development of coronary artery calcium among individuals with coronary artery calcium score of zero.

OBJECTIVES: The predictive value of thoracic aortic calcium (TAC) scores for coronary artery calcium (CAC) conversion (CAC>0) has not been fully evaluated. METHODS: We studied 1648 asymptomatic subjects (mean age 52 ± 9 years, 54% male) with baseline CAC = 0 who underwent repeat CAC scanning 5 years later (range 3-14 years). TAC was assessed in the ascending and descending aorta. CAC and TAC were measured using Agatston scores. The cohort was categorized by baseline TAC scores: TAC = 0 (n = 1381 subjects), TAC 1-9 (n = 54), TAC 10-99 (n = 132) and TAC≥100 (n = 81). Logistic regression was used to examine the predictive value of baseline TAC scores for CAC>0 on repeat scans. RESULTS: On repeat scanning, 380 subjects (23%) developed CAC>0. The frequency of CAC>0 increased progressively across baseline TAC (TAC = 0, TAC 1-9, TAC 10-99 and TAC≥100) 22%, 26%, 26% and 37%, respectively (P for trend = 0.0025). Univariate analysis showed baseline TAC ≥100 was a significant predictor of CAC>0 in repeat scans, while either TAC 1-9 or TAC 10-99 were not, OR 2.10 [CI 1.32-3.36], P = 0.002; OR 1.25 [CI 0.67-2.33], P = 0.5; OR 1.24 [CI 0.82-1.87], P = 0.3, respectively. In multivariable analysis, TAC ≥100 OR 1.90 [CI 1.08-3.33], P = 0.026, was a significant predictor of CAC>0, along with age, male gender, diabetes, hypertension, hypercholesterolemia and time between scans. CONCLUSIONS: The likelihood of conversion to CAC>0 increases with increasing TAC scores. TAC ≥ 100 is an independent predictor of CAC conversion. Subjects with CAC = 0 and extensive TAC (TAC ≥ 100) may merit earlier repeat scanning than those with no TAC or lower TAC scores.