Marcus Bauer

Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study.

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 1(st) 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 Harrells 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, R(2) = 2.73% to R(2) = 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.

Coronary Artery Calcification Is an Independent Stroke Predictor in the General Population

Background and Purpose— Coronary artery calcification (CAC) is a noninvasive marker of plaque load that predicts myocardial infarcts in the general population. Herein, we investigated whether CAC predicts stroke events in addition to established risk factors that are part of the Framingham risk score. Methods— A total of 4180 subjects from the population-based Heinz Nixdorf Recall study (45–75 years of age; 47.1% men) without previous stroke, coronary heart disease, or myocardial infarction were evaluated for stroke events over 94.9±19.4 months. Cox proportional hazards regressions were used to examine CAC as stroke predictor in addition to established vascular risk factors (age, sex, systolic blood pressure, low-density lipoprotein, high-density lipoprotein, diabetes mellitus, smoking, and atrial fibrillation). Results— Ninety-two incident strokes occurred (82 ischemic, 10 hemorrhagic). Subjects suffering a stroke had significantly higher CAC values at baseline than the remaining subjects (median, 104.8[Q1;Q3, 14.0;482.2] vs 11.2[0;106.2]; P<0.001). In a multivariable Cox regression, log10(CAC+1) was an independent stroke predictor (hazards ratio, 1.52 [95% confidence interval, 1.19–1.92]; P=0.001) in addition to age (1.35 per 5 years [1.15–1.59]; P<0.001), systolic blood pressure (1.25 per 10 mm Hg [1.14–1.37]; P<0.001), and smoking (1.75 [1.07–2.87]; P=0.025). CAC predicted stroke in men and women, particularly in subjects <65 years of age and independent of atrial fibrillation. CAC discriminated stroke risk specifically in participants belonging to the low (<10%) and intermediate (10%–20%) Framingham risk score categories. Conclusions— CAC is an independent stroke predictor in addition to classical risk factors in subjects at low or intermediate vascular risk.

Carotid intima-media thickness as a biomarker of subclinical atherosclerosis

Intima-media thickness of the carotid artery (CIMT) and its increase is associated with several cardiovascular risk factors and manifest cardiovascular diseases. CIMT is suggested to be an important biomarker of subclinical atherosclerosis. CIMT is measured in B-mode ultrasound images of the carotid tree as a typical double line of the arterial wall. CIMT is best visible in the measurement segment of the distal common carotid artery with lowest measurement variability. The measurement is most reliable over a one centimeter-segment with automatic or semi-automatic reading methods, which minimises reading errors. Further structured training of sonographer and reader is important for valid and reproducible results. CIMT is an accepted predictor for future cardiovascular events independent of age, gender and cardiovascular risk factors. Measurement seems to be best applicable in patients with intermediate risk in order to readjust cardiovascular risk. Plaques in the carotid tree and thickening of the CIMT are different atherosclerotic processes. From childhood to early adulthood CIMT is the only atherosclerotic marker of the carotid tree; plaques occur later in life. Both parameters contribute independently to risk assessment for future cardio-vascular events. Aims of this review are to outline measurement procedures, reproducibility, prognostic value and ability to discriminate healthy subject and patients with manifest disease in a practical and scientifically contemporary manner.

Subclinical Coronary Atherosclerosis Predicts Cardiovascular Risk in Different Stages of Hypertension Result of the Heinz Nixdorf Recall Study

Prehypertension is a frequent condition and has been demonstrated to increase cardiovascular risk. However, the association with coronary atherosclerosis as part of target organ damage is not well understood. We investigated the cross-sectional relationship and longitudinal outcome between blood pressure categories and coronary artery calcification (CAC), quantified by electron beam computed tomography, in 4181 participants from the population-based Heinz Nixdorf Recall Study cohort. At baseline, we observed a continuous increase in calcium scores with increasing blood pressure categories. During a median follow-up period of 7.18 years, 115 primary end points (2.8%; fatal and nonfatal myocardial infarction) and 152 secondary end points (3.6%; stroke and coronary revascularization) occurred. We observed a continuous increase in age- and risk factor-adjusted secondary endpoints (hazard ratios [95% CI]) with increasing blood pressure categories (referent: normotension) in men: prehypertension, 1.80 (0.53–6.13); stage 1 hypertension, 2.27 (0.66–7.81); and stage 2 hypertension, 4.10 (1.27–13.24) and in women: prehypertension, 1.13 (0.34–3.74); stage 1 hypertension, 2.14 (0.67–6.85); and stage 2 hypertension, 3.33 (1.24–8.90), respectively, but not in primary endpoints. Cumulative event rates were determined by blood pressure categories and the CAC. In prehypertension, the adjusted hazard ratios for all of the events were, for CAC 1 to 99, 2.05 (0.80–5.23; P=0.13); 100 to 399, 3.12 (1.10–8.85; P=0.03); and ≥400, 7.72 (2.67–22.27; P=0.0002). Risk of myocardial infarction and stroke in hypertension but also in prehypertension depends on the degree of CAC. This marker of target-organ damage might be included, when lifestyle modification and pharmacotherapeutic effects in prehypertensive individuals are tested to avoid exposure to risk and increase benefit.

Investigating Air Pollution and Atherosclerosis in Humans: Concepts and Outlook

Although ambient particulate matter contributes to atherosclerosis in animal models, its role in atherogenesis in humans needs to be established. This article discusses concepts, study design, and choice of health outcomes to efficiently investigate the atherogenic role of ambient air pollution, with an emphasis on early preclinical biomarkers of atherosclerosis that are unaffected by short-term exposure to air pollution (eg, carotid intima-media thickness [CIMT] and functional performance of the vessel). Air pollution studies using these end points are summarized. The CIMT is currently the most frequently used outcome in this field (6 studies). The continuous nature of CIMT, the lack of short-term variation, its relationship to atherosclerotic changes in the artery wall, its predictive value for coronary heart disease, and the noninvasiveness of the assessment make it a useful candidate for cross-sectional and longitudinal studies investigating the role of air pollution in atherogenesis.

Progression of coronary artery calcification seems to be inevitable, but predictable - results of the Heinz Nixdorf Recall (HNR) study

Aim Coronary artery calcification (CAC), as a sign of atherosclerosis, can be detected and progression quantified using computed tomography (CT). We develop a tool for predicting CAC progression. Methods and results In 3481 participants (45–74 years, 53.1% women) CAC percentiles at baseline (CACb) and after five years (CAC5y) were evaluated, demonstrating progression along gender-specific percentiles, which showed exponentially shaped age-dependence. Using quantile regression on the log-scale (log(CACb+1)) we developed a tool to individually predict CAC5y, and compared to observed CAC5y. The difference between observed and predicted CAC5y (log-scale, mean±SD) was 0.08±1.11 and 0.06±1.29 in men and women. Agreement reached a kappa-value of 0.746 (95% confidence interval: 0.732–0.760) and concordance correlation (log-scale) of 0.886 (0.879–0.893). Explained variance of observed by predicted log(CAC5y+1) was 80.1% and 72.0% in men and women, and 81.0 and 73.6% including baseline risk factors. Evaluating the tool in 1940 individuals with CACb>0 and CACb<400 at baseline, of whom 242 (12.5%) developed CAC5y>400, yielded a sensitivity of 59.5%, specificity 96.1%, (+) and (−) predictive values of 68.3% and 94.3%. A pre-defined acceptance range around predicted CAC5y contained 68.1% of observed CAC5y; only 20% were expected by chance. Age, blood pressure, lipid-lowering medication, diabetes, and smoking contributed to progression above the acceptance range in men and, excepting age, in women. Conclusion CAC nearly inevitably progresses with limited influence of cardiovascular risk factors. This allowed the development of a mathematical tool for prediction of individual CAC progression, enabling anticipation of the age when CAC thresholds of high risk are reached.

Association of obstructive sleep apnoea with subclinical coronary atherosclerosis.

BACKGROUND Accumulating evidence suggests a role of obstructive sleep apnoea (OSA) as a risk factor for coronary atherosclerosis. This study aimed i) to assess the prevalence of OSA in the general population and ii) to analyse the association of this disorder with traditional cardiovascular disease risk factors and subclinical coronary atherosclerosis. METHODS In a cross-sectional analysis of the Heinz Nixdorf Recall study a subgroup of 1604 subjects (791 men, age 50-80 years) underwent OSA screening. Furthermore, coronary artery calcium (CAC) was measured. OSA was defined as apnoea-hypopnoea index (AHI) ≥ 15/h. RESULTS OSA was observed in 29.1% of men and 15.6% of women. In a multiple linear regression analysis adjusted for risk factors AHI was associated with CAC in men aged ≤65 years (estimated log-transformed increase of CAC = 0.25, 95% confidence interval (CI) = -0.001-0.50, p = 0.051) and in women of any age (estimated log-transformed increase = 0.23, 95% CI = 0.04-0.41, p = 0.02). Doubling of the AHI was associated with a 19% increase of CAC in men aged ≤65 years and with a 17% increase in women of any age. CONCLUSIONS In the general population aged ≥50 years OSA is associated with subclinical atherosclerosis in men aged ≤65 years and in women of any age, independent of traditional cardiovascular risk factors.

The effect of age and risk factors on coronary and carotid artery atherosclerotic burden in males―Results of the Heinz Nixdorf Recall Study

BACKGROUND Increased arterial intima-media thickness (IMT) and coronary artery calcification (CAC) are measures of subclinical arteriosclerosis burden. Little is known, however, whether risk factors have an impact differently on atherosclerosis in these distinct vascular territories in the same individuals. METHODS AND DESIGN For 1620 men without coronary artery disease (CAD) and stroke, aged 45-75 years (59+/-8), IMT was measured 1cm proximal to the bulb in the common carotid artery (CCA). Both sides were measured and the average of the right and left artery were applied. Electron-beam CT was used to quantify coronary artery calcium (CAC). Cardiovascular risk factors were measured with standard techniques. RESULTS IMT increased with age from 0.64+/-0.12mm in the lowest decade (45-54 years) up to 0.76+/-0.14mm in the highest decade (65-74 years) (p<0.0001). CAC and IMT showed a significant correlation across the cohort. Individual variation in the extent of IMT and CAC was, however, high (r=0.26, p<0.0001). Standard risk factors had a similar impact on IMT and CAC relative to 5 years of ageing, except for diabetes and HDL, which had a higher impact on IMT than on CAC. The effect of diabetes mellitus on IMT exceeded the effect of 5 years of ageing. CONCLUSIONS IMT may be more sensitive to the atherosclerotic impact of diabetes than CAC, while blood pressure showed a higher effect on CAC. Thus, cardiovascular risk factors seem to have a different atherosclerotic impact on carotid arteries compared with coronary arteries.

A comparison of outcomes with coronary artery calcium scanning in unselected populations: The Multi-Ethnic Study of Atherosclerosis (MESA) and Heinz Nixdorf RECALL study (HNR)

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.

Association of epicardial adipose tissue and left atrial size on non-contrast CT with atrial fibrillation: The Heinz Nixdorf Recall Study

AIMS Epicardial adipose tissue (EAT) is increased in subjects with atrial fibrillation (AF). Likewise, EAT is associated with left atrial (LA) size, as itself is a strong predictor of AF. We aimed to determine the association of EAT and LA size as computed tomography (CT)-derived measures with prevalent and incident AF and investigated whether both measures independently predict AF. METHODS AND RESULTS Participants from the Heinz Nixdorf Recall study without known cardiovascular disease were included. At baseline, EAT, defined as fat volume inside the pericardial sac, and LA size, defined as an axial area at the level of the mitral valve, were quantified from non-contrast enhanced cardiac CT. AF was determined from electrocardiogram at baseline and also at 5-year follow-up examination. Overall, 3467 participants (age: 58.9 ± 7.6 years, 47% male) were included. Ninety-six subjects had AF (46 prevalent and 50 incident). A 1-standard deviation (SD) change of EAT was associated with nearly two-fold increased prevalence of AF in univariate analysis, which persisted after adjustment for AF risk factors [odds ratio (OR) (95% confidence interval, 95% CI): 1.38 (1.11-1.72), P = 0.003]. Ancillary adjusting for LA reduced the effect [1.26 (0.996-1.60), P = 0.054]. For incident AF, no relevant effect was observed for EAT when adjusting for risk factors [1.19 (0.88-1.61), P = 0.26]. In contrast, a 1-SD chance of LA was strongly associated with AF independently of EAT and risk factors [2.70 (2.22-2.20), P < 0.0001]. LA but not EAT as non-contrast CT-derived measures improved the prediction of AF over risk factors (receiver operating characteristics: 0.810-0.845, P = 0.025). CONCLUSION LA size from non-contrast CT is strongly associated with prevalent and incident AF and ultimately diminishes the link of EAT with AF.