Although the traditional Agatston coronary artery calcium (CAC) score is a powerful predictor of mortality, it is unknown if the regional distribution of CAC further improves cardiovascular risk ...prediction. We retrospectively studied 23,058 patients referred for Agatston CAC scoring, of whom 61% had CAC (n = 14,084). CAC distribution was defined as the number of vessels with CAC (0 to 4, including left main). For multivessel CAC, “diffuse” CAC was defined by decreasing percentage of CAC in the single most affected vessel and by ≤75% total Agatston CAC score in the most calcified vessel. All-cause mortality was ascertained through the social security death index. The mean age was 55 ± 11 years, with 69% men. There were 584 deaths (2.5%) over 6.6 ± 1.7 years. Considerable heterogeneity existed between the Agatston CAC score group and the number of vessels with CAC. In each CAC group, increasing number of vessels with CAC was associated with an increased mortality rate. After adjusting for age, gender, Agatston CAC score, and cardiovascular risk factors, increasing number of vessels with CAC was associated with higher mortality risk compared with single-vessel CAC (2-vessel: HR 1.61 95% CI 1.14 to 2.25, 3-vessel: 1.99 1.44 to 2.77, and 4-vessel: 2.22 1.53 to 3.23). “Diffuse” CAC was associated with a higher mortality rate in the CAC 101 to 400 and >400 groups. Left main CAC was associated with increased mortality risk. In conclusion, increasing number of vessels with CAC and left main CAC predict increased all-cause mortality and improve the prognostic power of the traditional Agatston CAC score.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Whether resting heart rate (RHR) predicts mortality independent of fitness is not well established, particularly among women. We analyzed data from 56,634 subjects (49% women) without known coronary ...artery disease or atrial fibrillation who underwent a clinically indicated exercise stress test. Baseline RHR was divided into 5 groups with <60 beats/min as reference. The Social Security Death Index was used to ascertain vital status. Cox hazard models were performed to determine the association of RHR with all-cause mortality, major adverse cardiovascular events, myocardial infarction, or revascularization after sequential adjustment for demographics, cardiovascular disease risk factors, medications, and fitness (metabolic equivalents). The mean age was 53 ± 12 years and mean RHR was 73 ± 12 beats/min. More than half of the participants were referred for chest pain; 81% completed an adequate stress test and mean metabolic equivalents achieved was 9.2 ± 3. There were 6,255 deaths over 11.0-year mean follow-up. There was an increased risk of all-cause mortality with increasing RHR (p trend <0.001). Compared with the lowest RHR group, participants with an RHR ≥90 beats/min had a significantly increased risk of mortality even after adjustment for fitness (hazard ratio 1.22, 95% confidence interval 1.10 to 1.35). This relationship remained significant for men, but not significant for women after adjustment for fitness (p interaction <0.001). No significant associations were seen for men or women with major adverse cardiovascular events, myocardial infarction, or revascularization after accounting for fitness. In conclusion, after adjustment for fitness, elevated RHR was an independent risk factor for all-cause mortality in men but not women, suggesting gender differences in the utility of RHR for risk stratification.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background The American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelines have significantly broadened the scope of candidates eligible for ...statin therapy. Objectives This study evaluated the implications of the absence of coronary artery calcium (CAC) in reclassifying patients from a risk stratum in which statins are recommended to one in which they are not. Methods MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6,814 men and women 45 to 84 years of age without clinical atherosclerotic cardiovascular disease (ASCVD) risk at enrollment. We excluded 1,100 participants (16%) on lipid-lowering medication, 87 (1.3%) without low-density lipoprotein levels, 26 (0.4%) with missing risk factors for calculation of 10-year risk of ASCVD, 633 (9%) >75 years of age, and 209 (3%) with low-density lipoprotein <70 mg/dl from the analysis. Results The study population consisted of 4,758 participants (age 59 ± 9 years; 47% males). A total of 247 (5.2%) ASCVD and 155 (3.3%) hard coronary heart disease events occurred over a median (interquartile range) follow-up of 10.3 (9.7 to 10.8) years. The new ACC/AHA guidelines recommended 2,377 (50%) MESA participants for moderate- to high-intensity statins; the majority (77%) was eligible because of a 10-year estimated ASCVD risk ≥7.5%. Of those recommended statins, 41% had CAC = 0 and had 5.2 ASCVD events/1,000 person-years. Among 589 participants (12%) considered for moderate-intensity statin, 338 (57%) had a CAC = 0, with an ASCVD event rate of 1.5 per 1,000 person-years. Of participants eligible (recommended or considered) for statins, 44% (1,316 of 2,966) had CAC = 0 at baseline and an observed 10-year ASCVD event rate of 4.2 per 1,000 person-years. Conclusions Significant ASCVD risk heterogeneity exists among those eligible for statins according to the new guidelines. The absence of CAC reclassifies approximately one-half of candidates as not eligible for statin therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background The transition from no coronary artery calcium (CAC) to detectable CAC is important, as even mild CAC is associated with increased cardiovascular events. We sought to characterize ...the anatomic distribution and burden of newly detectable CAC over 10-year follow-up. Methods We evaluated 3112 participants (mean age, 58 years; 64% female) with baseline CAC = 0 from the Multi-Ethnic Study of Atherosclerosis. Participants underwent repeat CAC testing at different time intervals (between 2–10 years after baseline) per the Multi-Ethnic Study of Atherosclerosis protocol. Among participants who developed CAC on a follow-up scan, we used logistic regression and marginal probability modeling to describe the coronary distribution and burden of new CAC by age, sex, and race after adjustment for cardiovascular risk factors and time to detection. Results A total of 1125 participants developed detectable CAC during follow-up with a mean time to detection of 6.1 ± 3 years. New CAC was most commonly isolated to 1 vessel (72% of participants), with the left anterior descending artery (44% of total) most commonly affected followed by the right coronary (12%), left circumflex (10%), and left main (6%). These patterns were similar across age, sex, and race. In multivariate models, residual predictors of multivessel CAC (28% of total) included male sex, African American or Hispanic race, hypertension, obesity, and diabetes. At the first detection of CAC >0, burden was usually low with median Agatston CAC score of 7.1 and <5% with CAC scores >100. Conclusion New-onset CAC most commonly involves just 1 vessel, occurs in the left anterior descending artery, and has low CAC burden. New CAC can be detected at an early stage when aggressive preventive strategies may provide benefit.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To determine which routinely collected exercise test variables most strongly correlate with survival and to derive a fitness risk score that can be used to predict 10-year survival.
This was a ...retrospective cohort study of 58,020 adults aged 18 to 96 years who were free of established heart disease and were referred for an exercise stress test from January 1, 1991, through May 31, 2009. Demographic, clinical, exercise, and mortality data were collected on all patients as part of the Henry Ford ExercIse Testing (FIT) Project. Cox proportional hazards models were used to identify exercise test variables most predictive of survival. A "FIT Treadmill Score" was then derived from the β coefficients of the model with the highest survival discrimination.
The median age of the 58,020 participants was 53 years (interquartile range, 45-62 years), and 28,201 (49%) were female. Over a median of 10 years (interquartile range, 8-14 years), 6456 patients (11%) died. After age and sex, peak metabolic equivalents of task and percentage of maximum predicted heart rate achieved were most highly predictive of survival (P<.001). Subsequent addition of baseline blood pressure and heart rate, change in vital signs, double product, and risk factor data did not further improve survival discrimination. The FIT Treadmill Score, calculated as percentage of maximum predicted heart rate + 12(metabolic equivalents of task) - 4(age) + 43 if female, ranged from -200 to 200 across the cohort, was near normally distributed, and was found to be highly predictive of 10-year survival (Harrell C statistic, 0.811).
The FIT Treadmill Score is easily attainable from any standard exercise test and translates basic treadmill performance measures into a fitness-related mortality risk score. The FIT Treadmill Score should be validated in external populations.
We hypothesized that anthropometric measures of abdominal obesity would have a stronger positive association with nonalcoholic fatty liver disease (NAFLD) measured by noncontrast computed tomography ...versus general measures of obesity. The Multiethnic Study of Atherosclerosis comprised participants aged 45 to 84 years free of known cardiovascular disease. We studied 4,088 participants with adequate liver and spleen computed tomography imaging and no previous use of oral steroids, class 3 antiarrhythmics, moderately heavy alcohol use, or cirrhosis. Prevalent NAFLD was defined as a liver:spleen Hounsfield attenuation ratio of <1. Multivariable log-linear regression modeled the association of 4 obesity measures—weight, body mass index (BMI), waist circumference, and waist-to-hip ratio—with prevalent NAFLD. Receiver-operator curve analysis compared NAFLD discrimination. Median age was 63 years, and 55% were women. For each obesity measure, adjusted prevalence ratios for NAFLD were fourfold to fivefold greater in the highest versus the lowest quartile (p <0.001). Waist circumference and BMI had the highest prevalence ratios, and waist circumference had the best discrimination, for NAFLD in the total population, although an abnormal BMI categorized subjects with NAFLD as well if not better than waist circumference. In ethnic-specific analysis, whites and Chinese had the strongest association of obesity and NAFLD compared with other ethnicities. In conclusion, although waist circumference provided the best discrimination for NAFLD, BMI may perform similarly well in clinical settings to screen for NAFLD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Aortic valve calcium (AVC) can be quantified on the same computed tomographic scan as coronary artery calcium (CAC). Although CAC is an established predictor of cardiovascular events, limited ...evidence is available for an independent predictive value for AVC. We studied a cohort of 8,401 asymptomatic subjects (mean age 53 ± 10 years, 69% men), who were free of known coronary heart disease and were undergoing electron beam computed tomography for assessment of subclinical atherosclerosis. The patients were followed for a median of 5 years (range 1 to 7) for the occurrence of mortality from any cause. Multivariate Cox regression models were developed to predict all-cause mortality according to the presence of AVC. A total of 517 patients (6%) had AVC on electron beam computed tomography. During follow-up, 124 patients died (1.5%), for an overall survival rate of 96.1% and 98.7% for those with and without AVC, respectively (hazard ratio 3.39, 95% confidence interval 2.09 to 5.49). After adjustment for age, gender, hypertension, dyslipidemia, diabetes mellitus, smoking, and a family history of premature coronary heart disease, AVC remained a significant predictor of mortality (hazard ratio 1.82, 95% confidence interval 1.11 to 2.98). Likelihood ratio chi-square statistics demonstrated that the addition of AVC contributed significantly to the prediction of mortality in a model adjusted for traditional risk factors (chi-square = 5.03, p = 0.03) as well as traditional risk factors plus the presence of CAC (chi-square = 3.58, p = 0.05). In conclusion, AVC was associated with increased all-cause mortality, independent of the traditional risk factors and the presence of CAC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objectives We sought to quantify the mortality rates associated with absent and low positive (CAC 1 to 10) coronary artery calcium (CAC). Background There is increasing interest in the absence of CAC ...as a “negative” cardiovascular risk factor. However, published event rates for individuals with no CAC vary, likely owing to differences in baseline risk, follow-up period, and outcome ascertainment. The prognostic significance of low CAC (CAC 1 to 10) is not well described. Methods Annualized all-cause mortality rates were assessed in 44,052 consecutive asymptomatic patients referred for CAC testing. Mean follow-up of the cohort was 5.6 ± 2.6 years (range 1 to 13 years). Results A total of 19,898 patients (45%) had no CAC on screening electron beam tomography, whereas 5,388 (12%) had low levels of CAC (CAC 1 to 10), and 18,766 (43%) had CAC >10. There were 104 deaths in those with no CAC (0.52%), 58 deaths in those with CAC 1 to 10 (1.06%), and 739 deaths in those with CAC >10 (3.96%). Annualized all-cause mortality rates for CAC = 0, CAC 1 to 10, and CAC >10 were 0.87, 1.92, and 7.48 deaths/1,000 person-years, respectively. The hazard ratio (HR) for all-cause mortality among CAC 1 to 10 versus CAC = 0 after adjustment for traditional risk factors was 1.99 (95% confidence interval CI: 1.44 to 2.75). Smoking (HR: 3.97, 95% CI: 2.75 to 5.41) and diabetes mellitus (HR: 3.36, 95% CI: 2.09 to 5.41) were associated with few events observed in CAC = 0 group. Conclusions In appropriately selected asymptomatic patients, the absence of CAC predicts excellent survival with 10-year event rates of approximately 1%. A finding of 0 CAC might be used as a rationale to emphasize lifestyle therapies rather than pharmacotherapy and to forgo repeated imaging studies. Individuals with low CAC score (CAC 1 to 10) are at increased risk above individuals with a 0 score and could be considered a distinct risk group by physicians and investigators.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Cardiorespiratory fitness protects against mortality; however, little is known about the benefits of improved fitness in individuals with a family history of coronary heart ...disease. We studied the association between cardiorespiratory fitness and risk of incident coronary heart disease and all-cause mortality, hypothesizing an inverse relationship similar to individuals without a family history of coronary heart disease. Methods We included 57,999 patients (53±13 years; 49% females; 29% Black), from the Henry Ford Exercise Testing (FIT) Project. Cardiorespiratory fitness was expressed in metabolic equivalents of task based on exercise stress testing. Family history was determined as self-reported coronary heart disease in a first-degree relative at any age. We used Cox proportional hazards models adjusted for demographics and cardiovascular disease risk factors to examine the association between cardiorespiratory fitness and risk of incident coronary heart disease and mortality over median (interquartile range; IQR) follow up of 5.5 (5.6) and 10.4 (6.8) years. Results Overall, 51% reported a positive family history. Each 1 unit MET increase was associated with lower incident coronary heart disease and mortality risk regardless of family history status. The HR (95% CI) for family history negative and family history positive were as follows: 0.87 (0.84, 0.89) and 0.87 (0.85,0.89) for incident coronary heart disease, and 0.83 (0.82, 0.84) and 0.83 (0.82, 0.85) for mortality, respectively. There was no significant interaction between family history and categorical cardiorespiratory fitness, sex, or age (P>0.05 for all). Conclusion Higher cardiorespiratory fitness is strongly protective in all patients regardless of family history status, supporting recommendations for regular exercise in those with a family history.
Baseline coronary artery calcification (CAC) accurately identifies coronary atherosclerosis and might improve prediction of future cardiac events. Serial assessment of CAC scores has been proposed ...for monitoring atherosclerosis progression and for assessing the effectiveness of medical therapies aimed at reducing cardiac risk. However, whether knowledge of progression of CAC scores over time further improves risk prediction is unclear. Several trials relating medical therapies to CAC progression have been performed without any formal guidelines on the definition of CAC progression and how it is best quantified. We conducted a comprehensive review of published reports on CAC progression. Increased CAC progression is associated with many known cardiac risk factors. We found that CAC progression correlates with worsening atherosclerosis and may facilitate prediction of future cardiac events. These findings support the notion that slowing CAC progression with therapeutic interventions might provide prognostic benefit. However, despite promising early data, such interventions (most notably with statin therapy) have not been shown to slow the progression of CAC in any randomized controlled trial to date, outside of post hoc subgroup analyses. Thus, routine quantification of CAC progression cannot currently be recommended in clinical practice. First, standards of how CAC progression should be defined and assessed need to be developed. In addition, there remains a need for further studies analyzing the effect of other cardiac therapies on CAC progression and cardiac outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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