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Background and aims: It was investigated whether there is a relationship between advanced atherosclerosis of the carotid artery and cancer. Method: The carotid Total Plaque Area (TPA), the maximum plaque thickness, and the cardiovascular risk based on Framingham calculator using body-mass-index were determined in healthy subjects using ultrasound. We compared the outcome in subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding) with and without statin treatment. The follow-up was collected as part of occupational health check-ups. Result: In 4207 healthy men aged 35-65 years (50±8 years) we found 578 subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding). A follow-up was available for 566 (97.9%) subjects. The average follow-up time was 48 months (range 0 to 139 months). Ten subjects were excluded because of missing data on treatment. A total number of 230 subjects was treated with a statin, 326 received no statin. Within the group of these subjects (54±6 years), 33 men died (15 cancer, 4 strokes, 11 heart attacks, 1 COPD, 1 sepsis, 1 cirrhosis of the liver). In the group with CVD death, two subjects were treated with a statin, 13 were untreated. In the group with cancer death, two subjects were treated with a statin, 13 were untreated. The death rate because of cancer and CVD was 1.7% for the treated subjects and 8.0% for the untreated subjects. In the group with low risk (n= 1890), six men died (2 traffic accidents, 1aneurysm bleeding, 2 cancer, 1 unclear, a follow-up examination has been completed for 43.9% (n= 830) of the subjects, mean follow-up time of 65 months (0-137 months). One man died (Parkinson) within the group with intermediate risk. In this group (n= 482) a follow-up examination has been completed for 55% (n= 265) with a mean follow-up time of 55 months (total range: 0-130 months). In the reference group (no atherosclerosis; n= 1257) follow-up has been completed in 38.3% (n= 482) with a mean follow-up time of 60 (0-145) months and nobody died. In 3203 healthy women aged 35-65 years nobody died of cancer. Conclusion: The development of cancer in men with advanced atherosclerosis of the carotid artery appears to be noticeable. The question of whether there is a causal relationship requires further investigations.

The quality of cardiovascular risk assessment and subsequent medical treatment for those at elevated risk is dependent on the precision of resource allocation. Several confounders may lead to unnecessary treatments, while those at elevated risk may remain untreated. Confounders occur both in calibration and discrimination. While calibration defines the threshold for individuals, which labels them as low, intermediate, high or very high subjects, discrimination describes the diagnostic accuracy of a test to detect those with future disease (Romanens et al., 2010). Once a test for cardiovascular risk assessment, such as the Framingham algorithm, has been derived from a population over decades, accuracy in different populations and continents still has to be undertaken (external validation). External validation is however difficult to obtain because contemporary performance can be assessed only after decades of observation of the outcome variable. Substitutions are however possible, e.g. with atherosclerosis imaging of carotid or coronary arteries (Romanens et al., 2017) or by measuring cardiovascular risk at the time of a cardiovascular event (Mortensen and Falk, 2017). Other important issues are the demographic or ethnic background of individuals assessed with such risk tools or the type of occupation. The working group on lipids and atherosclerosis (AGLA) recommends the use of cardiac or cardiovascular risk derived from PROCAM and SCORE respectively in Switzerland (Eckardstein, 2014). Based on predefined risk thresholds, a primary care subject is categorized into low, intermediate or high risk. For PROCAM, the categories are 0–9%, 10–19% and 20% or more; for SCORE, the categories are 0.0–0.9%, 1.0–4.9% and 5% or more (Piepoli et al., 2016). A major limitation to calculate global cardiovascular risk is present when single cardiovascular risk factors are high. Therefore, subjects with LDL above 5.0 mmol/l or systolic blood pressure above 160 mmHg are by definition high risk in Switzerland (for SCORE, the high-risk cutoffs are 8.0 mmol/l for total cholesterol and systolic blood pressure of 180 mmHg or more). The SCORE model based the risk algorithm on observations of fatal cardiovascular events in 12 European cohorts undergoing baseline examination between 1967 and 1991 (Conroy et al., 2003). In contrast, PROCAM was derived from working men, later extended to women using observations for myocardial infarction only (Assmann et al., 2007). Therefore, the accuracy of these risk assessment tools may be different in various populations. For the purpose of this study, we assess the agreement for a statin indication in German and Swiss subjects using the PROCAM/AGLA and the SCORE algorithm at various calibration thresholds.

Preventive therapy in primary care is guided by risk thresholds for future cardiovascular events. We aimed to assess whether the sensitivity of various risk calculators for the detection of subclinical carotid atherosclerosis (TPA80) could be improved by lowering risk thresholds in younger age groups. We compared sensitivity, specificity, and discriminatory performance of SCORE, SCORE-HDL, PROCAM, AGLA, FRAM and PCE coronary risk calculators to detect total plaque area > 80 mm2 (TPA80), a coronary risk equivalent, in age groups 40–55, 56–65, 66–75 from Germany (DE, N = 2942) and Switzerland (CH, N = 2202) during the years 2002 to 2016. All calculators showed good to moderate discriminatory performance to detect TPA80 with AUC ranging from 0.74 (CH-AGLA) to 0.87 (DE- SCORE), but the sensitivity of high risk risk thresholds varied widely from 39% for DE-FRAM-CVD to 5% for CH-AGLA. Lowering of the risk threshold increased sensitivity substantially at the expense of minor losses in specificity, but the sensitivity generally remained, Highlights • Low sensitivity of European and American risk calculators in two independent populations • Relatively high prevalence of advanced carotid atherosclerosis in people aged 40–65 • New thresholds for intermediate or high risk in younger subjects