Diagnostic Cardiac CT for the Improvement of Cardiovascular Event Prediction.

BACKGROUND: The aim of the long-term Heinz Nixdorf Recall Study (observation period 20 years) was to establish the extent to which computed tomography (CT) improves the predictability of cardiovascular events relative to determination of risk factors alone. METHODS: In the period 2000-2003, study staff examined 4355 probands (53% of them female) aged 45-75 years with no signs of cardiovascular disease. The Atherosclerotic Cardiovascular Disease (ASCVD) score was calculated on the basis of demographic data and cardiovascular risk factors. Cardiac CT was carried out over the same period and coronary artery calcification (CAC) was graded according to the Agatston score. RESULTS: The median duration of follow-up was 18.2 years for men and 17.8 years for women. Myocardial infarction or stroke occurred in 458 (11%) of the 4154 participants with complete data. Overall, estimation of risk using a combination of ASCVD score and CAC grade was superior to the ASCVD score alone-even after 10 and 20 years. Classification into established risk categories improved by 12.2% (95% confidence interval: [5.3%; 18.1%]). In the highest ASCVD risk category, we observed occurrence of a cardiovascular event over 20 years for 14% [5.0%; 23.1%] of probands with a CAC score = 0 but for 34.2% [27.5%; 41.4%] of those with a CAC score ≥ 400. In the lowest ASCVD risk category, an event occurred in 2.4% [1.4%; 3.7%] of probands with a CAC score = 0 and in 23.5% [2.3%; 35.8%] of those with a CAC score ≥ 400. CONCLUSION: Even after 20 years, individual risk prediction is improved by addition of CT-based determination of coronary artery calcification to the ASCVD score. Therefore, assessment of ASCVD risk factors should be complemented more widely by cardiac CT in the primary prevention of cardiovascular disease.

[Cardiac amyloidosis and aortic valve stenosis]. / Kardiale Amyloidose und Aortenklappenstenose.

Aortic valve stenosis in old age has become a topic of interest for cardiology and cardiac surgery after the development of transvascular and transluminal minimally invasive techniques for aortic valve implantation. The observation of amyloid deposits in surgically excised valvular material led to the diagnostics of amyloidosis of the myocardium, which was discovered in up to 20% of the patients who underwent valve implantation. Clinical signs of cardiac amyloidosis, such as carpal tunnel syndrome and ruptured distal biceps tendon should be taken into account. In addition to the electrocardiogram (ECG), echocardiogram and magnetic resonance imaging, 99mtechnetium bone scintigraphy plays a key diagnostic role. The simultaneous occurrence of severe aortic valve stenosis and amyloidosis explains the special hemodynamic situation of a low gradient with low blood flow in high-grade valve stenosis. The interventional or surgical valve implantation improves the prognosis for these patients, similarly to aortic valve stenosis alone, followed by a specific pharmaceutical treatment depending on the type of amyloidosis.

Sleep characteristics and progression of coronary artery calcification: Results from the Heinz Nixdorf Recall cohort study.

BACKGROUND AND AIMS: Sleep characteristics are associated with incident cardiovascular diseases (CVD), but there is a lack of studies on the association between sleep characteristics and incidence/progression of coronary artery calcification (CAC). METHODS: In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany, CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. In an analysis set of 3043 subjects (age at baseline 45-74 years; 47% men), we fitted logistic and linear regression models to assess associations between self-rated sleep characteristics (nocturnal and total sleep duration; napping; various sleep disorders) and CAC incidence/CAC progression. Progression was measured as 5-year progression factor, as categories of absolute CAC change, and additionally characterized as rapid or slow compared to an extrapolation of baseline CAC values. RESULTS: We observed barely any association between sleep characteristics and CAC progression regardless of the chosen statistical approach; associations between sleep and CAC incidence were slightly larger, e.g., the geometric mean of the 5-year CAC progression factor was 6.8% (95% confidence interval: -9.5; 25.9) larger for ≤5 h, 2.9% (-7.3; 14.3) larger for 5.1-6.9 h and 7.1% (-2.4; 15.7) smaller for ≥7.5 h total sleep compared to 7- <7.5 h total sleep. For subjects with any regular sleep disorder, the geometric mean of the 5-year CAC progression was 3.5% (-4.7; 11.2) smaller compared to subjects without any regular sleep disorder. CONCLUSIONS: In this German cohort study, sleep characteristics were barely associated with CAC progression.

Progression of coronary artery calcification is stronger in poorly than in well controlled diabetes: Results from the Heinz Nixdorf Recall Study.

AIM: To assess associations between HbA1c and progression of coronary artery calcification (CAC) in persons with and without diabetes. METHODS: In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany (N=3453, aged 45-74years), CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. At baseline, participants were divided into five groups: poorly (HbA1c≥7.0%) and well (HbA1c<7.0%) controlled previously known diabetes (group I/II); no previously known diabetes with HbA1c ≥6.5% (group III), HbA1c 5.7-6.4% (group IV), and HbA1c <5.7% (group V). We fitted linear, logistic and robust Poisson regression models to assess associations between diabetes group and PF5 (factor by which CAC after 5-year follow-up is larger than baseline CAC), and categories of CAC change, respectively. RESULTS: Relative to group V, adjusted percentage increase of the geometric mean of PF5 (95% CI) was: 69.1% (33.9%;113.6%), 15.4% (-5.6%;41.1%), -4.1% (-22.2%;18.2%), 4.2% (-5.4%;14.8%) for groups I-IV, respectively. The corresponding odds ratios for annual CAC increase ≥100 Agatston units (reference: <10) were 10.0 (4.8;20.6), 4.0 (2.1;7.6), 1.5 (0.7;3.2), and 1.1 (0.7;1.8). CONCLUSIONS: In known diabetes, CAC progression was stronger in poor diabetes control. For newly detected diabetes diagnosed by HbA1c ≥6.5%, associations with CAC progression were weak.

Accelerated progression of coronary artery calcification in hypertension but also prehypertension.

OBJECTIVE: To determine the role of hypertension for coronary artery calcification (CAC) progression. METHODS: The population-based Heinz Nixdorf Recall study recruited 4814 participants from a German urban population in 2000-2003. CAC was measured using electron-beam computed tomography at baseline and after 5 years. The present analyses refer to 3481 participants with repeat scan (coronary heart disease until 5 years excluded, age at baseline 45-74 years, and 53.1% women). Blood pressure (BP), Framingham risk factors, and antihypertensive medication were recorded at baseline. BP was staged according to Joint National Committee 7 guidelines. Participants under antihypertensive medication were classified as stage 2. CAC at 5 years was predicted from baseline using our dedicated, publicly available algorithm. CAC progression was accordingly classified as slow, expected, or rapid. RESULTS: Normotension was found in 20.5%, prehypertension in 27.2%, stage 1 hypertension in 15.8%, and stage 2 (ST2) in 36.5%. The frequency of rapid progression increases with BP stage (normotension: 16.7% to ST2: 21.1%, P = 0.004). Risk factor adjusted relative risk [RR (95% confidence interval), reference: normotension] of rapid progression was for prehypertension: 1.22 (0.98;1.51), stage 1: 1.29 (1.01;1.65), and ST2: 1.45 (1.17;1.79). Risk factor adjusted measures of CAC progression per 10 mmHg SBP were already elevated in women with BP below 140/90 mmHg: CAC onset, RR = 1.22 (1.07;1.40), rapid progression, RR = 1.17 (1.05;1.31), 5-year CAC progression, 6.7% (0.5;13.4). In men below 140/90 mmHg, only RR of rapid progression was considerably increased [RR = 1.11 (0.96;1.29)]. CONCLUSION: CAC progression, a sign of ongoing target organ damage, is already accelerated in prehypertensive patients, a substantial proportion of our urban population.

Blood serum atherogenicity and coronary artery calcification.

The phenomenon of blood serum atherogenicity was described as the ability of human serum to induce lipid accumulation in cultured cells. The results of recent two-year prospective study in asymptomatic men provided the evidence for association between the changes in serum atherogenicity and dynamics of carotid intima-media thickness progression. The present study was undertaken to test the hypothesis that blood serum atherogenicity and its changes in dynamics may be associated with accumulation of coronary calcium in subclinical atherosclerosis. It was performed in 782 CHD-free participants of The Heinz Nixdorf RECALL (Risk Factors, Evaluation of Coronary Calcium and Lifestyle) Study, in whom blood samples have been taken at the baseline and at the end of 5-year follow-up. Opposite to the previous findings, the changes in serum atherogenicity did not correlate neither with the extent of coronary artery calcification, nor with the changes in Agatston CAC score. There was a moderate but significant rise in serum atherogenicity after 5-year followup period, and the same dynamics was observed for Agatston CAC score, but not for convenient lipid-related risk factors. The absence of association of the changes in serum atherogenicity with the changes in Agatston CAC score, along with previous findings, provides a point of view that serum-induced intracellular cholesterol accumulation is not related to the processes of calcium deposition in arterial wall, since the last one reflects the progression of already existing subclinical atherosclerotic lesions.

Effect of smoking and other traditional risk factors on the onset of coronary artery calcification: results of the Heinz Nixdorf recall study.

BACKGROUND: Coronary artery calcium (CAC) indicates coronary atherosclerosis and can be present in very early stages of the disease. The conversion from no CAC to any CAC reflects an important step of the disease process as cardiovascular risk is increased in persons even with mildly elevated CAC. We sought to identify risk factors that determined incident CAC>0 in men and women from an unselected general population with a special focus on the role of smoking. METHODS: All 4814 persons that were initially studied in the Heinz Nixdorf Recall Study were invited to participate in the follow-up examination after 5.1 ± 0.3 years. All traditional Framingham risk factors were quantified using standard techniques. Smokers were categorized in never, former and present smokers. The CAC scores were measured from EBCT using the Agatston method. RESULTS: Overall, out of 342 men and 919 women with zero CAC at baseline, 107 (31.3%) men and 210 (22.9%) women had CAC>0 at second examination. In multivariable analysis, age (OR estimate per 5 years: 1.34 (95%CI: 1.21-1.47)), LDL cholesterol (per 10 mg/dL: 1.05 (95%CI: 1.01-1.10)), systolic blood pressure (per 10 mmHg: 1.19 (95%CI: 1.11-1.28)) and current smoking (1.49 (95%CI: 1.04-2.15)) were independent predictors of CAC onset. The probability of CAC onset steadily increased with age from 23.3% (men) and 15.3% (women) at age 45-49 years to 66.7% (men) and 42.9% (women) at age 70-74 years. The difference in age-dependent conversion rates was quantified by years between reaching a given level of CAC onset probability. We found a consistent pattern with respect to smoking status: presently (formerly) smoking middle-aged men convert to positive CAC 10 (5) years earlier than never smokers, for women (middle-aged to elderly) this time span is 8 (5) years. CONCLUSION: Several traditional CVD risk factors are associated with CAC onset during 5 years follow-up. CAC onset is accelerated by approximately 10 (5) years for present (former) compared to never smokers.

Gender-specific association of coronary artery calcium and lipoprotein parameters: the Heinz Nixdorf Recall Study.

BACKGROUND: Coronary atherosclerosis can be detected by computed tomography. The amount of coronary artery calcification (CAC) is related to cardiovascular risk factors, the strength of the gender specific relation between lipoprotein parameters and CAC has not extensively been studied. Especially, the role of routinely determined lipoproteins in contrast to less common and computed lipid parameters (e.g. ratios) remains to be clarified. METHODS AND RESULTS: The study cohort (n = 3956, 52% women, age 45-75 years) was randomly selected from three cities of a German metropolitan area. Lipoproteins-low-and high density lipoprotein (LDL-C/HDL-C), total cholesterol, apolipoprotein A-1 and B (apoA-1/apoB) as well as lipoprotein (a) (Lp(a)) were measured, while non-HDL-C was calculated. All participants received an electron-beam computed tomography (EBCT) for quantification of CAC. Adjusted for age and cardiovascular risk factors, CAC increased by a factor of 1.97 (1.51-2.57, 95% CI) and 1.94 (1.53-2.45, 95% CI) comparing the fourth to the first quartile of LDL-C for men and women, respectively. This association with LDL-C was also found after dichotomization of CAC at thresholds >0, ≥ 100 and ≥ 400. The best association of CAC was, however, found to be apoB and the second best was non HDL-C, in both men and women. For apoB, the model including all risk factors reached an explained variance for CAC of 20.2% in men and of 21.6% in women. When using LDL-C as a given parameter according to the current practice and advice, HDL-C in men and apoB in women provided an additional but small benefit. CONCLUSION: ApoB showed the best association with CAC compared to all other tested lipoproteins. Neither the ratio LDL-C/HDL-C nor apoB/apoA-1, or Lp(a) revealed a closer association with CAC. While lipoproteins are related to CAC more closely in women than in men, their association with CAC is, however, not particularly strong. Our results may influence primary and secondary prevention advices in order to improve detection of subclinical atherosclerosis, for which lipoprotein parameters can only play a minor role.

Coronary risk stratification, discrimination, and reclassification improvement based on quantification of subclinical coronary atherosclerosis: the Heinz Nixdorf Recall study.

OBJECTIVES: The purpose of this study was to determine net reclassification improvement (NRI) and improved risk prediction based on coronary artery calcification (CAC) scoring in comparison with traditional risk factors. BACKGROUND: CAC as a sign of subclinical coronary atherosclerosis can noninvasively be detected by CT and has been suggested to predict coronary events. METHODS: In 4,129 subjects from the HNR (Heinz Nixdorf Recall) study (age 45 to 75 years, 53% female) without overt coronary artery disease at baseline, traditional risk factors and CAC scores were measured. Their risk was categorized into low, intermediate, and high according to the Framingham Risk Score (FRS) and National Cholesterol Education Panel Adult Treatment Panel (ATP) III guidelines, and the reclassification rate based on CAC results was calculated. RESULTS: After 5 years of follow-up, 93 coronary deaths and nonfatal myocardial infarctions occurred (cumulative risk 2.3%; 95% confidence interval: 1.8% to 2.8%). Reclassifying intermediate (defined as 10% to 20% and 6% to 20%) risk subjects with CAC <100 to the low-risk category and with CAC ≥400 to the high-risk category yielded an NRI of 21.7% (p = 0.0002) and 30.6% (p < 0.0001) for the FRS, respectively. Integrated discrimination improvement using FRS variables and CAC was 1.52% (p < 0.0001). Adding CAC scores to the FRS and National Cholesterol Education Panel ATP III categories improved the area under the curve from 0.681 to 0.749 (p < 0.003) and from 0.653 to 0.755 (p = 0.0001), respectively. CONCLUSIONS: CAC scoring results in a high reclassification rate in the intermediate-risk cohort, demonstrating the benefit of imaging of subclinical coronary atherosclerosis. Our study supports its application, especially in carefully selected individuals with intermediate risk.

Association of pericoronary fat volume with atherosclerotic plaque burden in the underlying coronary artery: a segment analysis.

OBJECTIVE: We aimed to determine, whether the amount of local pericoronary fat volume is associated with the presence of plaque burden in the underlying coronary artery segment. METHODS: We assessed 311 coronary segments from ECG-gated contrast-enhanced dual-source computed tomography for presence of plaque as well as segmental pericoronary fat volume. For pericoronary fat evaluation, regions of interest were manually traced containing any fat surrounding a coronary artery segment, with the myocardial wall, the pericardial sac and other coronary segments as outer border. RESULTS: Per each doubling of pericoronary fat volume, we observed an 2.5-fold increase in the presence of plaque in the underlying coronary segment in unadjusted models (95% confidence interval [CI] 1.87-3.27, p<0.001), which remained after adjustment for traditional cardiovascular risk factors (odds ratio [OR] 3.07 [2.16-4.35], p<0.001) and when additionally accounting for overall pericardial fat volume (OR 2.68 [1.90-3.79], p<0.001). Associations were similar in all coronary artery segments and not related to the type of plaque (calcified or non-calcified, p<0.01 for all). CONCLUSION: Pericoronary fat is associated with atherosclerosis in the coronary arteries. Our results support the hypothesis that perivascular fat depots may function as a local endocrine risk factor in atherosclerosis development.

Smoking cessation and subclinical atherosclerosis--results from the Heinz Nixdorf Recall Study.

BACKGROUND: Smoking accounts for more than 5 million years of potential life lost per year in the US alone. Leading causes of smoking attributable mortality are acute atherothrombotic complications of coronary heart disease (CHD). Smoking cessation is a key issue in preventive medicine, but quantitative data on its benefit for the coronary arteries are sparse. METHODS: The Heinz Nixdorf Recall Study is an ongoing population-based, prospective cohort study, with 4814 participants aged 45-74 years (49.8% men). Baseline data of 4078 participants without history of established coronary heart disease or stroke are included in this report. Electron beam-computed tomography allows for non-invasive quantification of coronary artery calcium (CAC). We estimate the risk-related ageing of coronary arteries from multivariable regression of CAC on smoking behavior, sex, age and risk factors. RESULTS: Smoking 20 cigarettes per day since the age of 16 is associated with a CAC burden which is found in a person 10 years older who has never smoked (both sexes). Smoking cessation at 45, 55 or 65 leads to CAC at the age of 75 that would have been reached 9, 6 or 3 years earlier, respectively, had smoking been continued. CONCLUSIONS: In individuals without overt CHD, present smokers are about 10 years older in 'coronary artery age' than never smokers. The accumulation of CAC is accelerated by smoking and slows down after smoking cessation, but advanced CAC is persistent for a long period. These quantitative findings strongly support smoking cessation measures as early as possible, to prevent accelerated arterial ageing.

Cardiovascular risk factors and signs of subclinical atherosclerosis in the Heinz Nixdorf Recall Study.

INTRODUCTION: Modern investigation modalities allow markers of atherosclerosis to be detected at a subclinical stage. The aim of the study was to analyze the prevalence of these markers in relation to traditional risk factors. METHODS: The population based study included 4814 participants, aged 45 to 75 years, with a response rate of 55.8% of those contacted. The patients' history, psychosocial and environmental risk factors were assessed. RESULTS: The prevalence of obesity was 26.2% in men and 28.1% in women, 26% of men and 21% of women were smokers. Hypertension was found in 46% of men and 31% of women, diabetes in 9.3% of men and 6.3% of women. Markers of subclinical peripheral arterial disease were found in 6.4% of men and 5.1% of women, of subclinical carotid artery disease in 43.2% and 30.7%, and of subclinical coronary artery calcification in 82.3% and 55.2%, respectively. The prevalence of coronary calcification measured using an Agatston Score >100 was in 40% in men and 15% in women, using a score >400, 16.8% and 4.5%, respectively. DISCUSSION: A high prevalence of subclinical atherosclerosis was found in the older population. The follow-up period will demonstrate whether the detection of markers of subclinical atherosclerosis will improve risk stratification beyond that offered by traditional risk factors.

Sex related cardiovascular risk stratification based on quantification of atherosclerosis and inflammation.

OBJECTIVES: An ongoing population-based cohort study was used to assess the prevalence of risk factors, signs of inflammation based on the degree of high sensitive C-reactive protein (hs-CRP) and subclinical atherosclerosis using electron beam computed tomography for detection of coronary artery calcification (CAC). We evaluated the sex related cardiovascular risk stratification based on quantification of subclinical atherosclerosis and inflammation. BACKGROUND: The National Cholesterol Education Program in Adult Treatment Panel III (NCEP ATP III) suggests using CAC and hs-CRP in individuals at intermediate risk. The effect on risk stratification was not yet tested in the general population. METHODS: In the Heinz Nixdorf Recall study 4066 (93.2%) subjects without and 280 (6.8%) of 4345 subjects with coronary artery disease (CAD) (age 45-75 years) were screened in whom data for CAC, hs-CRP, and all risk factors for calculating the Framingham risk score (FRS) were available. This subset of participants was representative of the overall population. Age-adjusted prevalence rate ratios (RR) for prevalence of CAD in relation to risk factors were determined. Framingham risk score groups and NCEP ATP III-based risk categories were calculated. Alterations in risk classification were analyzed using three CAC and hs-CRP categories each: (1) CAC<100, 100-399 and > or =400 or >75th percentile, respectively, (2) hs-CRP< or =1, 1-3, >3mg/L, and (3) a combined CAC and hs-CRP score. RESULTS: Highest RRs of CAD were found for high CAC versus low CAC in men (RR=18.2, 95% CI=10.6-31.3) and for the combined CAC+hs-CRP index in women (RR=11.0, 95% CI=5.1-23.6, both p<0.0001). For high versus low hs-CRP-values a significant RR was found for women only (RR=2.5, 95% CI=1.3-4.6, p<0.01). RRs for other risk factors like hyperlipidemia, HDL, smoking, BMI>30 kg/m(2) were much smaller showing sex differences as well. Thirty percent males and 71% females were classified as low NCEP ATP III risk, 38% and 20% as intermediate and 31% and 9% as high risk. Adding CAC and hs-CRP to NCEP ATP risk categories changed distribution of risk categories considerably with strong differences between sexes. This sex dependence in the magnitude of change in risk categories nearly vanished, when the combined index of CAC and hs-CRP was used. CONCLUSIONS: NCEP ATP III risk categories are significantly and sex-dependently altered using CAC and hs-CRP. CAC is suggested to be of highest value in men; hs-CRP seems to be of complementary value only in women. Measuring atherosclerotic inflammation may improve sex-related risk prediction in a general population.

Population-based assessment of subclinical coronary atherosclerosis using electron-beam computed tomography.

AIMS: Coronary artery calcification (CAC) is determined as a measure of the extent of coronary atherosclerosis and can be used for expanded cardiovascular risk stratification. It was our aim to establish reference CAC scores in a population-based unselected European cohort. METHODS AND RESULTS: The Heinz Nixdorf Recall study (HNR) recruited a total of 4814 participants aged 45-74 years. Cardiovascular risk factors and medications were recorded, and CAC was measured using electron-beam CT (EBCT). CAC score distribution was compared with previous studies in subjects who were self-referred, volunteered, or were physician-referred. Of the 4472 (92.9%) subjects free of clinical coronary artery disease, the CAC score was available in 4275 (95.3%) (2027 men, 2248 women). CAC scores were lower in particular in the higher age groups (> or = 60 years) in men than in the previous studies. Also, in most age groups (except the highest, 70-74 years), subjects with no cardiovascular medications had significantly lower CAC scores than subjects using cardiovascular medications. CONCLUSIONS: The current report characterises the distribution of EBCT-derived CAC scores in a European unselected population. Compared with previous reports, CAC scores were lower in our cohort, in particular in subjects not receiving cardiovascular medications. Classification of the CAC score may underestimate true risk if previously published referral cohorts are used as the reference.

Prognostic value of extensive coronary calcium quantities in symptomatic males--a 5-year follow-up study.

AIMS: Coronary calcium scores (CSs) have been shown to predict future events in patients presenting for first-time evaluation of CAD. Long-term outcome data on symptomatic subjects with advanced CAD are limited. In this study, we evaluated the prognostic value of very high coronary CSs in symptomatic males undergoing angiography and analyzed the impact of event definitions on identification of risk predictor's. METHODS AND RESULTS: Fifty consecutive symptomatic males with electron beam computed tomography (EBT)-based CSs >1000 were matched 1:2 by age with symptomatic males with scores between 400-1000 and 100-400. All 150 patients underwent coronary angiography. CAD risk factors were ascertained. Events were analyzed after 5 years for: (1) hard coronary events (coronary death and myocardial infarction); (2) overall hard events (adding stroke and non-coronary deaths); and (3) all events (including long-term revascularizations). During follow-up, 17 deaths, two infarctions and three strokes occurred in 21 patients; 38 patients underwent 43 revascularizations. Events occurred earlier and more frequently in patients with scores >1000. Left main disease was the only independent predictor of hard coronary events (hazard ratio, 4.5; 95% confidence interval, 1.1-17.8). Left main disease (4.3; 1.4-13.0) and CSs (1.7; 1.1-2.5) independently predicted overall hard events. Only CSs>90th percentile independently predicted all events (2.5; 1.3-4.8). CONCLUSIONS: Symptomatic males with extensive CSs carry an even higher risk for future events than other symptomatic males with advanced CAD. In these patients, EBT-based calcified plaque burden and angiographic indices of disease severity may have a complementary role in predicting future cardiovascular events.

Assessment of clinically silent atherosclerotic disease and established and novel risk factors for predicting myocardial infarction and cardiac death in healthy middle-aged subjects: rationale and design of the Heinz Nixdorf RECALL Study. Risk Factors, Evaluation of Coronary Calcium and Lifestyle.

BACKGROUND: In view of consistently high cardiovascular morbidity and mortality rates, international efforts are aimed at developing tools for more precise risk prediction to allow preventive treatment targeted at high-risk individuals. Direct visualization of anatomic, preclinical atherosclerotic disease has the potential for individualized risk discrimination. Further, a variety of risk factors are actively evaluated, including markers of the activity of atherosclerotic disease, thrombogenic risk, and genetic polymorphisms. METHODS: The Heinz Nixdorf RECALL (Risk Factors, Evaluation of Coronary Calcium and Lifestyle) study is a population-based, prospective cohort study of the comparative value of modern risk stratification techniques for "hard" cardiac events. It is designed and powered to define the relative risk associated with the specific extent of coronary atherosclerosis measured by means of electron-beam computed tomography (EBCT)-derived coronary calcium quantities for myocardial infarction and cardiac death in 5 years in 4200 males and females aged 45 to 75 years in an unselected urban population from the large, heavily industrialized Ruhr area. Additionally, the predictive values of conventional cardiovascular risk factors, new candidate and socioeconomic risk factors, certain genetic polymorphisms, and direct signs of subclinical disease are examined with the ankle-brachial index, resting and stress electrocardiograms, and determination of carotid artery intima-media thickness. Prospective clinical risk-benefit and health economic analyses are an inherent part of the study. Study findings with established clinical significance are reported to the participants, but the EBCT findings are withheld until the conclusion of the study. CONCLUSIONS: The Heinz Nixdorf RECALL study will define appropriate methods for identifying high-risk subgroups in the general urban population who may derive the greatest benefit from preventive treatment.