Coronary Artery Calcium Scores and Atherosclerotic Cardiovascular Disease Risk Stratification in Smokers.

This study assessed the utility of the pooled cohort equation (PCE) and/or coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk assessment in smokers, especially those who were lung cancer screening eligible (LCSE). The U.S. Preventive Services Task Force recommended and the Centers for Medicare & Medicaid Services currently pays for annual screening for lung cancer with low-dose computed tomography scans in a specified group of cigarette smokers. CAC can be obtained from these low-dose scans. The incremental utility of CAC for ASCVD risk stratification remains unclear in this high-risk group. Of 6,814 MESA (Multi-Ethnic Study of Atherosclerosis) participants, 3,356 (49.2% of total cohort) were smokers (2,476 former and 880 current), and 14.3% were LCSE. Kaplan-Meier, Cox proportional hazards, area under the curve, and net reclassification improvement (NRI) analyses were used to assess the association between PCE and/or CAC and incident ASCVD. Incident ASCVD was defined as coronary death, nonfatal myocardial infarction, or fatal or nonfatal stroke. Smokers had a mean age of 62.1 years, 43.5% were female, and all had a mean of 23.0 pack-years of smoking. The LCSE sample had a mean age of 65.3 years, 39.1% were female, and all had a mean of 56.7 pack-years of smoking. After a mean of 11.1 years of follow-up 13.4% of all smokers and 20.8% of LCSE smokers had ASCVD events; 6.7% of all smokers and 14.2% of LCSE smokers with CAC = 0 had an ASCVD event during the follow-up. One SD increase in the PCE 10-year risk was associated with a 68% increase risk for ASCVD events in all smokers (hazard ratio: 1.68; 95% confidence interval: 1.57 to 1.80) and a 22% increase in risk for ASCVD events in the LCSE smokers (hazard ratio: 1.22; 95% confidence interval: 1.00 to 1.47). CAC was associated with increased ASCVD risk in all smokers and in LCSE smokers in all the Cox models. The C-statistic of the PCE for ASCVD was higher in all smokers compared with LCSE smokers (0.693 vs. 0.545). CAC significantly improved the C-statistics of the PCE in all smokers but not in LCSE smokers. The event and nonevent net reclassification improvements for all smokers and LCSE smokers were 0.018 and -0.126 versus 0.16 and -0.196, respectively. In this well-characterized, multiethnic U.S. cohort, CAC was predictive of ASCVD in all smokers and in LCSE smokers but modestly improved discrimination over and beyond the PCE. However, 6.7% of all smokers and 14.2% of LCSE smokers with CAC = 0 had an ASCVD event during follow-up.

Leigh A ，McEvoy JW ，Garg P ，Carr JJ ，Sandfort V ，Oelsner EC ，Budoff M ，Herrington D ，Yeboah J ... -  《-》

Use of coronary artery calcium testing to improve coronary heart disease risk assessment in a lung cancer screening population: The Multi-Ethnic Study of Atherosclerosis (MESA).

Assessment of coronary artery calcium (CAC) during lung cancer screening chest computed tomography (CT) represents an opportunity to identify asymptomatic individuals at increased coronary heart disease (CHD) risk. We determined the improvement in CHD risk prediction associated with the addition of CAC testing in a population recommended for lung cancer screening. We included 484 out of 6814 Multi-Ethnic Study of Atherosclerosis (MESA) participants without baseline cardiovascular disease who met U.S. Preventive Service Task Force CT lung cancer screening criteria and underwent gated CAC testing. 10 year-predicted CHD risks with and without CAC were calculated using a validated MESA-based risk model and categorized into low (<5%), intermediate (5%-10%), and high (≥10%). The net reclassification improvement (NRI) and change in Harrell's C-statistic by adding CAC to the risk model were subsequently determined. Of 484 included participants (mean age = 65; 39% women; 32% black), 72 (15%) experienced CHD events over the course of follow-up (median = 12.5 years). Adding CAC to the MESA CHD risk model resulted in 17% more participants classified into the highest or lowest risk categories and a NRI of 0.26 (p = 0.001). The C-statistic improved from 0.538 to 0.611 (p = 0.01). CHD event rates were high in this lung cancer screening eligible population. These individuals represent a high-risk population who merit consideration for CHD prevention measures regardless of CAC score. Although overall discrimination remained poor with inclusion of CAC scores, determining whether those reclassified to an even higher risk would benefit from more aggressive preventive measures may be important.

Garg PK ，Jorgensen NW ，McClelland RL ，Leigh JA ，Greenland P ，Blaha MJ ，Yoon AJ ，Wong ND ，Yeboah J ，Budoff MJ ... -  《-》

Coronary Artery Calcium Volume and Density: Potential Interactions and Overall Predictive Value: The Multi-Ethnic Study of Atherosclerosis.

This study sought to determine the possibility of interactions between coronary artery calcium (CAC) volume or CAC density with each other, and with age, sex, ethnicity, the new atherosclerotic cardiovascular disease (ASCVD) risk score, diabetes status, and renal function by estimated glomerular filtration rate, and, using differing CAC scores, to determine the improvement over the ASCVD risk score in risk prediction and reclassification. In MESA (Multi-Ethnic Study of Atherosclerosis), CAC volume was positively and CAC density inversely associated with cardiovascular disease (CVD) events. A total of 3,398 MESA participants free of clinical CVD but with prevalent CAC at baseline were followed for incident CVD events. During a median 11.0 years of follow-up, there were 390 CVD events, 264 of which were coronary heart disease (CHD). With each SD increase of ln CAC volume (1.62), risk of CHD increased 73% (p < 0.001) and risk of CVD increased 61% (p < 0.001). Conversely, each SD increase of CAC density (0.69) was associated with 28% lower risk of CHD (p < 0.001) and 25% lower risk of CVD (p < 0.001). CAC density was inversely associated with risk at all levels of CAC volume (i.e., no interaction was present). In multivariable Cox models, significant interactions were present for CAC volume with age and ASCVD risk score for both CHD and CVD, and CAC density with ASCVD risk score for CVD. Hazard ratios were generally stronger in the lower risk groups. Receiver-operating characteristic area under the curve and Net Reclassification Index analyses showed better prediction by CAC volume than by Agatston, and the addition of CAC density to CAC volume further significantly improved prediction. The inverse association between CAC density and incident CHD and CVD events is robust across strata of other CVD risk factors. Added to the ASCVD risk score, CAC volume and density provided the strongest prediction for CHD and CVD events, and the highest correct reclassification.

Criqui MH ，Knox JB ，Denenberg JO ，Forbang NI ，McClelland RL ，Novotny TE ，Sandfort V ，Waalen J ，Blaha MJ ，Allison MA ... -  《-》

Greater Volume but not Higher Density of Abdominal Aortic Calcium Is Associated With Increased Cardiovascular Disease Risk: MESA (Multi-Ethnic Study of Atherosclerosis).

Abdominal aortic calcium (AAC) and coronary artery calcium (CAC) independently and similarly predict cardiovascular disease (CVD) events. The standard AAC and CAC score, the Agatston method, upweights for greater calcium density, thereby modeling higher calcium density as a CVD hazard. Computed tomography scans were used to measure AAC and CAC volume and density in a multiethnic cohort of community-dwelling individuals, and Cox proportional hazard was used to determine their independent association with incident coronary heart disease (CHD, defined as myocardial infarction, resuscitated cardiac arrest, or CHD death), cardiovascular disease (CVD, defined as CHD plus stroke and stroke death), and all-cause mortality. In 997 participants with Agatston AAC and CAC scores >0, the mean age was 66±9 years, and 58% were men. During an average follow-up of 9 years, there were 77 CHD, 118 CVD, and 169 all-cause mortality events. In mutually adjusted models, additionally adjusted for CVD risk factors, an increase in ln(AAC volume) per standard deviation was significantly associated with increased all-cause mortality (hazard ratio=1.20; 95% confidence interval, 1.08-1.33; P<0.01) and an increased ln(CAC volume) per standard deviation was significantly associated with CHD (hazard ratio=1.17; 95% confidence interval, 1.04-1.59; P=0.02) and CVD (hazard ratio=1.20; 95% confidence interval, 1.05-1.36; P<0.01). In contrast, both AAC and CAC density were not significantly associated with CVD events. The Agatston method of upweighting calcium scores for greater density may be inappropriate for CVD risk prediction in both the abdominal aorta and coronary arteries.

Forbang NI ，Michos ED ，McClelland RL ，Remigio-Baker RA ，Allison MA ，Sandfort V ，Ix JH ，Thomas I ，Rifkin DE ，Criqui MH ... -  《-》

Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019: The MESA Study (Multi-Ethnic Study of Atherosclerosis).

Cainzos-Achirica M ，Miedema MD ，McEvoy JW ，Al Rifai M ，Greenland P ，Dardari Z ，Budoff M ，Blumenthal RS ，Yeboah J ，Duprez DA ，Mortensen MB ，Dzaye O ，Hong J ，Nasir K ，Blaha MJ ... -  《-》