Abstract Objectives The aim of this study was to assess the difference in indication for statin therapy by European Society of Cardiology (ESC) versus American Heart Association/American College of ...Cardiology (AHA/ACC) guidelines and to quantify the potential additional role of coronary artery calcification (CAC) score over updated guidelines in a primary prevention cohort. Background Recently, ESC and AHA/ACC updated the guidelines regarding statin therapy in primary prevention. Methods In 3,745 subjects (59 ± 8 years of age, 47% men) from the population based longitudinal Heinz Nixdorf Recall cohort study without cardiovascular disease or lipid-lowering therapy at baseline CAC score was assessed between 2000 and 2003. Subjects remained unaware of their initial CAC score. Statin indication was determined according to 2012 ESC and 2013 AHA/ACC guidelines based on subjects individual baseline characteristics. Results The frequency of statin recommendation was lower according to ESC compared to AHA/ACC guidelines (34% vs. 56%; p < 0.0001), whereas low CAC score (<100) was common in subjects with statin indication by both guidelines (59% for ESC, 62% for AHA/ACC). During 10.4 ± 2.0 years of follow-up, 131 myocardial infarctions occurred. For ESC recommendations, CAC score differentiated risk for subjects without (1.0 95% confidence interval (CI): 0.4 to 1.5 vs. 6.5 95% CI: 4.1 to 8.9 coronary events per 1,000 person-years for CAC 0 vs. ≥100) and with statin indication (2.6 95% CI: 0.6 to 4.7 vs. 9.9 95% CI: 7.3 to 12.5 per 1,000 person-years for CAC 0 vs. ≥100). Likewise, CAC score stratified proportions experiencing events subjects with statin indication according to AHA/ACC (2.7 95% CI: 1.1 to 4.2 vs. 9.1 95% CI: 7.0 to 11.0 per 1,000 person-years for CAC 0 vs. ≥100), whereas event rate in subjects without statin indication was low (1.1 95% CI: 0.65 to 1.68 per 1,000 person-years). Conclusions Current ESC and AHA/ACC guidelines lead to markedly different recommendation regarding statin therapy in a German primary prevention cohort. Quantification of CAC score in addition to the guidelines improves stratification between subjects at high versus low risk for coronary events, indicating that CAC scoring may help to match intensified risk factor modification to atherosclerotic plaque burden as well as actual risk while avoiding therapy in subjects with low coronary atherosclerosis that have low 10-year event rate.
Objectives This study sought to determine whether epicardial fat volume predicts coronary events in the general population. Background Epicardial adipose tissue (EAT) is suggested to promote plaque ...development in the coronary artery tree. Methods We quantified EAT volume in participants from the prospective population-based Heinz Nixdorf Recall cohort study free of cardiovascular disease. Incident coronary events were assessed during a follow-up period of 8.0 ± 1.5 years. Multivariable association of EAT with cardiovascular risk factors, coronary artery calcification (CAC), and coronary events was assessed using regression analysis. Results From the overall 4,093 participants (age 59.4 years, 47% male), 130 subjects developed a fatal or nonfatal coronary event. Incidence of coronary events increased by quartile of EAT (0.9% vs. 4.7% for 1st and 4th quartile, respectively, p < 0.001). Doubling of EAT was associated with a 1.5-fold risk of coronary events when adjusting for cardiovascular risk factors (hazard ratio HR 95% confidence interval (CI): 1.54 1.09 to 2.19), which remained unaltered after further adjustment for CAC score (HR 95% CI: 1.50 1.07 to 2.11). For discrimination of subjects with events from those without, we observed a trend for improvement of Harrell's C and explained variance by EAT over traditional cardiovascular risk factors, which, however, did not reach statistical significance (0.720 to 0.730 for risk factors alone and with EAT added, respectively, p = 0.10, R2 = 2.73% to R2 = 2.92%, time-dependent integrated discrimination improvement = 0.196%). Conclusions Epicardial fat is associated with fatal and nonfatal coronary events in the general population independent of traditional cardiovascular risk factors and complements information from cardiac computed tomography above the CAC score.
Objectives This study sought to determine whether the evaluation of the combined presence of coronary artery calcium (CAC) and high-sensitivity C-reactive protein (hsCRP) improves discrimination and ...stratification of hard coronary events and all-cause mortality in the general population. Background Coronary atherosclerosis is a chronic inflammatory disease. Both hsCRP as a measure of inflammation and CAC as a measure of coronary plaque burden have been shown to improve risk appraisal. Methods Framingham risk variables, hsCRP, and CAC were measured in 3,966 subjects without known coronary artery disease or acute inflammation. After 5 years, incident coronary deaths, nonfatal myocardial infarction, and all-cause mortality were determined. Results CAC and hsCRP independently predicted 91 coronary events (adjusted hazard ratios HRs: log2 (CAC+1) = 1.25 95% confidence interval (CI): 1.16 to 1.34, p < 0.0001; hsCRP = 1.11 95% CI: 1.02 to 1.21, p = 0.019) and 130 deaths (adjusted HRs: log2 (CAC+1) = 1.12 95% CI: 1.06 to 1.19, p < 0.0001; hsCRP = 1.11 95% CI: 1.04 to 1.19, p = 0.004). For coronary events, net reclassification improvement (NRI) was 23.8% (p = 0.0007) for CAC and 10.5% (p = 0.026) for hsCRP. Adding CAC to Framingham risk variables and hsCRP further improved discrimination of coronary risk but not vice versa. Among persons without CAC, those with hsCRP >3 mg/l versus <3 mg/l had a significantly higher coronary risk (p = 0.006). For all-cause mortality, integrated discrimination improvement (IDI) was positive when CAC or hsCRP were added to age and sex (+0.51%, p < 0.001 and +0.43%, p = 0.012, respectively). Adjusted HRs in the highest versus lowest category of a risk index derived from established CAC and hsCRP thresholds (i.e., CAC = 100 and hsCRP = 3 mg/l) were 5.92 (95% CI: 3.14 to 11.16) for coronary events and 3.02 (95% CI: 1.82 to 5.01) for all-cause mortality (p < 0.0001 each). The adjusted HR for coronary events in intermediate risk subjects was 6.98 (95% CI: 2.47 to 19.73), p < 0.001. Conclusions The risk of coronary events and all-cause mortality that is mediated by the presence of coronary atherosclerosis and systemic inflammation can be estimated by CAC and hsCRP. An improvement in coronary risk prediction and discrimination was predominantly driven by CAC, whereas hsCRP appears to have a role especially in persons with very low CAC scores.
Abstract Background Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. Thus, identifying subjects with unknown AF or at higher risk for ...future AF in the general population is of importance. B-type natriuretic peptide (BNP) is linked with silent cardiac diseases. We evaluated the association of BNP with incident AF in a large population-based cohort study. Methods We included subjects from the population-based Heinz Nixdorf Recall study without known coronary heart disease, prior stroke, history of open heart surgery, heart-device therapy, or prevalent AF at baseline. Association of continuous and binary (≥31 pg/ml for male, ≥45 pg/ml for female) BNP with incident AF after 5 years was assessed using logistic regression analysis. Results A total of 3067 subjects (mean age 58.9 years, 47.9% male) were included in this analysis. Subjects with incident AF ( n = 42) had higher levels of BNP (median (Q1; Q3): 33.2 pg/ml (19.4; 50.5) vs. 16.9 pg/ml (9.2; 30.2)). Likewise, BNP was associated with incidence of AF both in univariate model and when adjusting for AF risk factors (odds ratio (OR) (95% confidence interval (CI)): BNP as continuous variable: 1.27 (1.09; 1.47), p = 0.002; BNP as binary variable: 2.68 (1.41; 5.11) with AF risk factor adjustment). Notably, especially younger subjects (<60 years) showed stronger association with incident AF than older ones (OR (95%CI) for dichotomized BNP: 7.20 (1.60; 32.49), p = 0.01 for <60 years, vs. 2.13 (0.89; 5.09), p = 0.09 for 60–70 years, and 4.40 (1.29; 14.97), p = 0.02 for >70 years). Conclusions Elevated levels of BNP are associated with significant excess of incident AF, independent of traditional AF risk factors in the general population. Gender-specific BNP thresholds may help in prevention by detecting unknown or future AF, which carries a high risk of stroke events.
The measurement of carotid intima-media thickness (CIMT) is a valid method to quantify levels of atherosclerosis. The present study was conducted to compare the strengths of associations between CIMT ...and cardiovascular risk factors in two different populations.
The Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR) are two population-based prospective cohort studies of subclinical cardiovascular disease. All Caucasian subjects aged 45 to 75 years from these cohorts who were free of baseline cardiovascular disease (n = 2,820 in HNR, n = 2,270 in MESA) were combined. CIMT images were obtained using B-mode sonography at the right and left common carotid artery and measured 1 cm starting from the bulb.
In both studies, age, male sex, and systolic blood pressure showed the strongest association (P < .0001 for each) for a higher CIMT. The mean of mean far wall CIMT was slightly higher in MESA participants (0.71 vs 0.67 mm). Almost all significant variables were consistent between the two cohorts in both magnitude of association with CIMT and statistical significance, including age, sex, smoking, diabetes, cholesterol levels, and blood pressure. For example, the association with systolic blood pressure was (ΔSD = 0.011; 95% confidence interval, 0.0009 to 0.014) per mm Hg in MESA and (ΔSD = 0.010; 95% confidence interval, 0.005 to 0.021) per mm Hg in HNR. This consistency persisted throughout the traditional (Framingham) risk factors.
A comparison of the associations between traditional cardiovascular risk factors and CIMT across two culturally diverse populations showed remarkable consistency.
Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. This study aims to determine whether current standard magnetic resonance imaging (MRI) is providing ...markers that can distinguish between subjects with amnestic MCI (aMCI), nonamnestic MCI (naMCI), and healthy controls (HCs).
A subset of 126 MCI subjects and 126 age-, gender-, and education-appropriate HCs (mean age, 70.9 years) were recruited from 4157 participants in the longitudinal community-based Heinz Nixdorf Recall Study. The burden of white matter hyperintensities (WMHs), cerebral microbleeds, and brain atrophy was evaluated on transversal MR images from a single 1.5-T MR scanner by two blinded neuroradiologists. Logistic regression and receiver-operating characteristic analysis were used for statistical analysis.
Occipital WMH burden was significantly increased in aMCI, but not in naMCI relative to HCs (P = .01). The combined MCI group showed brain atrophy relative to HCs (P = .01) pronounced at caudate nuclei (P = .01) and temporal horn level (P = .004) of aMCI patients and increased at the frontal and occipital horns of naMCI patients compared to either aMCI or HCs. Microbleeds were equally distributed in the MCI and control group, but more frequent in aMCI (22 of 84) compared to naMCI subjects (3 of 23).
In his cohort, increased occipital WMHs and cortical and subcortical brain atrophies at temporal horn and caudate nuclei level distinguished aMCI from naMCI subjects and controls. Volumetric indices appear of interest and should be assessed under reproducible conditions to gain diagnostic accuracy.
Abstract Background Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk ...prediction. However, to date, no risk score incorporating CAC has been developed. Objectives The goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors. Methods Algorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study). Results Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p < 0.0001). External validation in both the HNR and DHS studies provided evidence of very good discrimination and calibration. Harrell’s C-statistic was 0.779 in HNR and 0.816 in DHS. Additionally, the difference in estimated 10-year risk between events and nonevents was approximately 8% to 9%, indicating excellent discrimination. Mean calibration, or calibration-in-the-large, was excellent for both studies, with average predicted 10-year risk within one-half of a percent of the observed event rate. Conclusions An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies.
Abstract Background The Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf RECALL (Risk factors, Evaluation of Coronary Calcium and Lifestyle Factors) study (HNR) differed in regard ...to informing physicians and patients of the results of their subclinical atherosclerosis. Objective This study investigates whether the association of the presence of coronary calcium with incident nonfatal and fatal cardiovascular events is different among these 2 large, population-based observational studies. Methods All white subjects aged 45 to 75 years, free of baseline cardiovascular disease were included (n = 2232 in MESA; n = 3119 HNR participants). We studied the association between coronary calcium and event rates at 5 years, including hard cardiac events (myocardial infarction, cardiac death, resuscitated cardiac arrest), and separately added revascularizations and strokes (fatal and nonfatal) to determine adjusted hazard ratios. Results Both cohorts showed low coronary heart disease (including revascularization) rates with zero coronary calcium (1.13% and 1.16% over 5 years in MESA and HNR, respectively) and increasing significantly in both groups with Agatston score 100 to 399 (6.71% and 4.52% in MESA and HNR, respectively) and Agatston score > 400 (12.5% and 13.54% in MESA and HNR, respectively) and showing strong independent predictive values for Agatston scores of 100 to 399 and >400, despite multivariable adjustment for risk factors. Risk factor-adjusted 5-year revascularization rates were nearly identical for HNR and MESA and were generally low for both studies (1.4% 45 of 3119 for HNR and 1.9% 43 of 2232 for MESA) over 5 years. Conclusions Across 2 culturally diverse populations, Agatston score >400 is a strong predictor of events. High Agatston score did not statistically result in revascularization, and knowledge of the presence of coronary calcium did not increase revascularizations.
Abstract Objectives This study sought to determine whether epicardial adipose tissue (EAT) volume predicts the progression of coronary artery calcification (CAC) score in the general population. ...Background EAT predicts coronary events and is suggested to influence the development of atherosclerosis. Methods We included 3,367 subjects (mean age 59 ± 8 years; 47% male) from the population-based Heinz Nixdorf Recall study without known coronary artery disease at baseline. CAC was quantified from noncontrast cardiac electron beam computed tomography at baseline and after 5 years. EAT was defined as fat volume inside the pericardial sac and was quantified from axial computed tomography images. Association of EAT volume with CAC progression (logCAC(follow-up) + 1 − logCAC(baseline) + 1) was depicted as percent progression of CAC + 1 per SD of EAT. Results Subjects with progression of CAC above the median had higher EAT volume than subjects with less CAC change (101.1 ± 47.1 ml vs. 84.4 ± 43.4 ml; p < 0.0001). In regression analysis, 6.3% (95% confidence interval CI: 2.3% to 10.4%; p = 0.0019) of progression of CAC + 1 was attributable to 1 SD of EAT, which persisted after adjustment for risk factors (6.1% 95% CI: 1.2% to 11.2%; p = 0.014). For subjects with a CAC score of >0 to ≤100, progression of CAC + 1 by 20% (95% CI: 11% to 31%; p < 0.0001) was attributable to 1 SD of EAT. Effect sizes decreased with CAC at baseline, with no relevant link for subjects with a CAC score ≥400 (0.2% 95% CI: −3.5% to 4.2%; p = 0.9). Likewise, subjects age <55 years at baseline showed the strongest association of EAT with CAC progression (20.6% 95% CI: 9.7% to 32.5%; p < 0.0001). Interestingly, the effect of EAT on CAC progression was more pronounced in subjects with low body mass index (BMI), and decreased with degree of adiposity (BMI ≤25 kg/m2 : 19.8% 95% CI: 9.2% to 31.4%; p = 0.0001, BMI >40 kg/m2 : 0.8% 95% CI: −26.7% to 38.9%; p = 0.96). Conclusions EAT is associated with the progression of CAC, especially in young subjects and subjects with low CAC score, suggesting that EAT may promote early atherosclerosis development.
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