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Importance: Besides age, other discriminators of atherosclerotic cardiovascular disease (ASCVD) risk are needed in older adults., Objectives: To examine the predictive ability of coronary artery calcium (CAC) score vs age for incident ASCVD and how risk prediction changes by adding CAC score and removing only age from prediction models., Design, Setting, and Participants: We conducted an analysis of pooled US population-based studies, including the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Results were compared with 2 European cohorts, the Rotterdam Study and the Heinz Nixdorf Recall Study. Participants underwent CAC scoring between 1998 and 2006 using cardiac computed tomography. The participants included adults older than 60 years without known ASCVD at baseline., Exposures: Coronary artery calcium scores., Main Outcomes and Measures: Incident ASCVD events including coronary heart disease (CHD) and stroke., Results: The study included 4778 participants from 3 US cohorts, with a mean age of 70.1 years; 2582 (54.0%) were women, and 2431 (50.9%) were nonwhite. Over 11 years of follow-up (44 152 person-years), 405 CHD and 228 stroke events occurred. Coronary artery calcium score (vs age) had a greater association with incident CHD (C statistic, 0.733 vs 0.690; C statistics difference, 0.043; 95% CI of difference, 0.009-0.075) and modestly improved prediction of incident stroke (C statistic, 0.695 vs 0.670; C statistics difference, 0.025; 95% CI of difference, -0.015 to 0.064). Adding CAC score to models including traditional cardiovascular risk factors, with only age being removed, provided improved discrimination for incident CHD (C statistic, 0.735 vs 0.703; C statistics difference, 0.032; 95% CI of difference, 0.002-0.062) but not for stroke. Coronary artery calcium score was more likely than age to provide higher category-free net reclassification improvement among participants who experienced an ASCVD event (0.390; 95% CI, 0.312-0.467 vs 0.08; 95% CI -0.001 to 0.181) and to result in more accurate reclassification of risk for ASCVD events among these individuals. The findings were similar in the 2 European cohorts (n = 4990)., Conclusions and Relevance: Coronary artery calcium may be an alternative marker besides age to better discriminate between lower and higher CHD risk in older adults. Whether CAC score can assist in guiding the decision to initiate statin treatment for primary prevention in older adults requires further investigation.

Objective: To investigate the relationship between LV size as determined by non-contrast enhanced cardiac CT with incident cardiovascular disease in the general population free of clinical cardiovascular disease., Methods: LV axial area was quantified from non-contrast CT in axial, end-diastolic images at a mid-ventricular slice in participants from the population-based Heinz Nixdorf recall study, free of cardiovascular disease (n=3926, 59±8years, 53%female). LV size index (LVI) was defined as the quotient of LV area and body surface area. Major CV events (coronary events, stroke, CV death) were assessed during follow-up. Association of LVI with events was assessed using Cox regression analysis in unadjusted and multivariable adjusted models., Results: During 8.0±1.5years of follow-up, 219 subjects developed a major CV event. Those with events had larger LVI at baseline (2258±352 vs. 2149±276 mm2/m2, p<0.0001). In univariate analysis, increase of LVI by 1 standard deviation was associated with 40% higher risk of events (HR(95%CI):1.41(1.26-1.59), p<0.0001). Associations remained statistically significant after adjustment for CV risk factors (1.24(1.10-1.40), p=0.0007) and when further adjusting for CAC (1.21(1.07-1.37), p=0.003). There was a trend towards stronger association for subjects with low CAC-score (CAC<100:1.41(1.16-1.71), p=0.0005, CAC≥100:1.24(1.06-1.44), p=0.006) in univariate analysis which persisted after multivariable adjustment (CAC<100: 1.41(1.14-1.73), p=0.001, CAC≥100: 1.12(0.96-1.31), p=0.16)., Conclusion: CT-derived LV size is associated with incident major CV events independent of traditional risk factors and CAC-score in a population-based cohort and may improve the prediction of hard events especially in subjects with low CAC-scores., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: We develop a new diabetes CHD risk estimator using traditional risk factors plus coronary artery calcium (CAC), ankle-brachial index (ABI), high sensitivity C-reactive protein, family history of CHD, and carotid intima-media thickness and compared it with United Kingdom Prospective Diabetes study (UKPDS), Framingham risk and the NCEP/ATP III risk scores in type 2 diabetes mellitus (T2DM)., Methods and Results: We combined data from T2DM without clinical CVD in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (N = 1343). After a mean follow-up of 8.5 years, 85 (6.3%) participants had incident CHD. Among the novel risk markers, CAC best predicted CHD independent of the FRS [hazard ratio: HR (95% CI): log (CAC +25):1.69 (1.45-1.97), p < 0.0001; CAC categories: CAC ≤ 25 as reference, >25 and ≤125:2.29 (0.87-5.95), >125 and ≤400: 3.87 (1.57-9.57), >400: 5.97 (2.57-13.84), respectively). The MESA-HNR diabetes CHD risk score has better accuracy for the main outcome versus the FRS or UKPDS [area under curve (AUC) of 0.76 vs. 0.70 and 0.69, respectively; all p < 0.05]. The MESA-HNR risk score improved risk classification versus the FRS (net reclassification improvement (NRI) = 0.19 and integrated discrimination improvement (IDI) = 0.046, p < 0.05) and UKPDS (NRI = 0.215 and IDI = 0.046, p < 0.05). Compared with the ATP III guidelines, the MESA-HNR score has an NRI of 0.74 for the main outcome., Conclusions: This new CHD risk estimator has better discriminative ability for incident CHD than the FRS, UKPDS, and the ATP III/NCEP recommendations in a multi-ethnic cohort with T2DM., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

A parental history of premature coronary heart disease (CHD) is an established risk factor for CHD events in descendants. The study aim was to investigate whether subclinical coronary artery calcification (CAC) differs between asymptomatic individuals (a) without a parental CHD history, (b) with a parental history and (c) without knowledge of parental CHD history. The inclusion of individuals without knowledge of parental CHD history is a new approach. We also differentiated between CHD of mother and father to gain insight into their individual contributions. Data was obtained for 4,301 subjects aged 45-75 years free of overt CHD from the baseline screening of the population-based Heinz Nixdorf Recall study. CAC, measured by electron-beam computed tomography, was modeled conducting logistic regressions. Model 1 included family history, Model 2 was adjusted for age (and gender) and Model 3 added common CHD risk factors. The CAC score was dichotomized using the age and sex-specific 75th percentile. The odds ratio (OR) for CAC ≥ age and sex-specific 75th percentile was 1.33 among individuals with parental premature CHD history (95 % confidence interval [95 %CI]: 1.08, 1.63), which did not change after full adjustment (OR 1.40, 95 %CI: 1.13, 1.74). Individuals with an unknown biological father or mother had a high chance of elevated CAC scores (fully adjusted; father: OR 1.38, 95 %CI: 1.01, 1.90, mother: OR 1.86, 95 %CI: 0.90, 3.84) compared to the reference group. The current study showed an association between parental CHD history and CAC independent of common CHD risk factors. This association affirms the use of parental CHD history in cardiovascular risk assessment among asymptomatic adults in routine practice. The observation that individuals who did not know their mother or father are prone to increased CAC scores needs further confirmation in large scale studies.

For selected indications, coronary computed tomographic (CT) angiography is an established clinical technology for evaluation in patients suspected of having or known to have coronary artery disease. In coronary CT angiography, image quality is highly dependent on heart rate, with heart rate reduction to less than 60 beats per minute being important for both image quality and radiation dose reduction, especially when single-source CT scanners are used. β-Blockers are the first-line option for short-term reduction of heart rate prior to coronary CT angiography. In recent years, multiple β-blocker administration protocols with oral and/or intravenous application have been proposed. This review article provides an overview of the indications, efficacy, and safety of β-blockade protocols prior to coronary CT angiography with respect to different scanner techniques. Moreover, implications for radiation exposure and left ventricular function analysis are discussed., (© RSNA, 2010.)

Traffic is one of the major sources of environmental pollution in metropolitan areas, emitting pollutants such as particulate matter and noise. Epidemiological evidence links both particulate matter (PM) and noise to cardiovascular disease and increased cardiovascular mortality. Short-term exposure to traffic may trigger acute cardiovascular events. Long-term residential traffic exposure is associated with the degree of subclinical atherosclerosis, prevalence of coronary heart disease and incidence of myocardial infarction. This review will present recent epidemiological findings regarding long-term exposure to traffic and its association with coronary heart disease, using results from the Heinz Nixdorf Recall Study, an ongoing prospective cohort study of 4814 unselected participants living in three large adjacent cities of the highly industrialized Ruhr Area in western Germany. Special focus is placed on the association of long-term traffic exposure with subclinical atherosclerosis, the major underlying pathology for cardiovascular disease.

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.

Objective: To study the role of the coronary microcirculation in response to different-sized microemboli, we measured changes in intramyocardial microvascular blood volume (Bv), perfusion (F) and transit time (TT) and also microvascular patterns of injury., Methods: Bv, F and TT were quantitated in 24 pigs at baseline and again 2 min after repeat injections of 10- or 100-microm microspheres at rest or during intracoronary adenosine infusion. The association of Bv and TT was assessed in the microsphere pigs and in nine control pigs. Microvascular injury was studied on gross-pathologic and histologic samples., Results: At rest, initial injection of 10-microm microspheres led to increases in Bv and F, but progressively decreased with additional injections. In contrast, even small numbers of 100-microm microspheres always led to decreases in Bv and F. Injection of microspheres during adenosine-induced vasodilation always resulted in decreases in peak Bv and F irrespective of their diameters, but microvascular TTs remained unaltered. In control pigs, however, TTs were inversely related to adenosine-induced changes in Bv. Histologically, 100-microm microspheres resulted in patchy distribution of microcirculatory plugging, while 10-microm microspheres induced contiguous hemorrhagic myocardial injury., Conclusion: Microsphere-induced changes in intramyocardial Bv and F and the associated pattern of myocardial injury are related to the size of embolized microvessels and the initial perfusion state. Microvascular functional volume reserve mechanisms appear to play a key role accompanying flow- and TT-preservation.

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. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with diabetes mellitus (DM) have an increased risk for periprocedural complications and adverse cardiac events after percutaneous coronary intervention. We addressed the potential for coronary microvascular obstruction and restenosis in patients with and without DM undergoing stenting for saphenous vein bypass graft (SVG) stenosis under protection with a distal occlusion/aspiration device. Methods SVG plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Percent diameter stenosis was determined from quantitative coronary angiography before, immediately after and 6 months after stent implantation. Coronary aspirate was retrieved during stent implantation and divided into particulate debris and plasma. Total calcium, several vasoconstrictors, and tumor necrosis factor (TNF)α in particulate debris and coronary aspirate plasma were determined. Results Patients with and without DM had similar plaque volume, but larger necrotic core and greater particulate debris release in patients with than without DM (20.3±2.7 vs. 12.7±2.6% and 143.9±19.3 vs. 75.1±10.4 mg, Pvs. 5.1±2.4 pmol/mg and 2.2±0.7 vs. 1.1±0.2 pmol/L, Pvs. 6.34±1.11%, PP Conclusion In diabetics, particulate debris and coronary aspirate plasma contained more TNFα, which might reflect the activity of the underlying atherosclerotic process. Trial registration URL: http://www.clinicaltrials.gov/ct2/results?term=NCT01430884; unique identifier: NCT01430884

IMPORTANCE The role of coronary artery calcium (CAC) testing for guiding preventive strategies among women at low cardiovascular disease (CVD) risk based on the American College of Cardiology and American Heart Association CVD prevention guidelines is unclear. OBJECTIVE To assess the potential utility of CAC testing for CVD risk estimation and stratification among low-risk women. DESIGN, SETTING, AND PARTICIPANTS Women with 10-year atherosclerotic CVD (ASCVD) risk lower than 7.5% from 5 large population-based cohorts: the Dallas Heart Study (United States), the Framingham Heart Study (United States), the Heinz Nixdorf Recall study (Germany), the Multi-Ethnic Study of Atherosclerosis (United States), and the Rotterdam Study (the Netherlands). The 5 cohorts were selected based on the availability of CAC data in a sizable group of low-risk women from the general population together with the long detailed follow-up data. Across the cohorts, events were assessed from the date of CAC scan (performed from 1998 through 2006) until January 1, 2012; January 1, 2014; or March 6, 2015. Fixed-effects meta-analysis was conducted to combine the results of the 5 studies. EXPOSURES CAC score by computed tomography. MAIN OUTCOMES AND MEASURES Main outcome was incident ASCVD, including nonfatal myocardial infarction, coronary heart disease (CHD) death, and stroke. Association of CAC with ASCVD was examined using Cox proportional hazards models. To assess whether CAC was associated with improved ASCVD risk predictions beyond the traditional risk factors, the C statistic and the continuous net reclassification improvement (cNRI) index were calculated. RESULTS Among 6739 women with low ASCVD risk from the 5 studies, mean age ranged from 44 to 63 years and CAC was present in 36.1%. Across the cohorts, median follow-up ranged from 7.0 to 11.6 years. A total of 165 ASCVD events occurred (64 nonfatal myocardial infarctions, 29 CHD deaths, and 72 strokes), with the ASCVD incidence rates ranging from 1.5 to 6.0 per 1000 person-years. Compared with the absence of CAC (CAC = 0), presence of CAC (CAC >0) was associated with an increased risk of ASCVD (incidence rates per 1000 person-years, 1.41 for CAC absence vs 4.33 for CAC presence; difference, 2.92 [95% CI, 2.02-3.83]; multivariable-adjusted hazard ratio, 2.04 [95% CI, 1.44-2.90]). The addition of CAC to traditional risk factors improved the C statistic from 0.73 (95% CI, 0.69-0.77) to 0.77 (95% CI, 0.74-0.81) and provided a cNRI of 0.20 (95% CI, 0.09-0.31) for ASCVD prediction. CONCLUSIONS AND RELEVANCE Among women at low ASCVD risk, CAC was present in approximately one-third and was associated with an increased risk of ASCVD and modest improvement in prognostic accuracy compared with traditional risk factors. Further research is needed to assess the clinical utility and cost-effectiveness of this additional accuracy. [ABSTRACT FROM AUTHOR]

Stent implantation into atherosclerotic coronary arteries releases particulate debris and soluble substances that contribute to impaired microvascular perfusion. Here we addressed the potential for microvascular obstruction in patients with stenotic native right coronary arteries (nRCA) compared with saphenous vein grafts on right coronary arteries (SVG-RCA). We enrolled symptomatic, male patients with stable angina pectoris and a flow-limiting stenosis in their nRCA or SVG-RCA (n = 18/18). Plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation under protection with a distal occlusion/aspiration device and divided into particulate debris and plasma. The release of catecholamines, endothelin, serotonin, thromboxane B2, and tumor necrosis factor-α was measured. The response of rat mesenteric arteries with intact (+E) and denuded (-E) endothelium to aspirate plasma (without and with selective endothelin receptor blockade) was normalized to that by potassium chloride (KClmax = 100%). Plaque volume and composition were not different between nRCA and SVG-RCA. There was less particulate debris (65 ± 8 vs. 146 ± 23 mg; P < 0.05) and more endothelin release (5.8 ± 0.8 vs. 1.3 ± 0.7 pg/ml; P < 0.05) in nRCA than in SVG-RCA, whereas the release of the other mediators was not different. Aspirate from nRCA induced stronger vasoconstriction than that from SVG-RCA [nRCA, 78 ± 6% (+E)/84 ± 5% (-E); SVG-RCA, 59 ± 6% (+E)/68 ± 3% (-E); P < 0.05 nRCA vs. SVG-RCA], which was attenuated by a nonspecific endothelin and a specific endothelin receptor A antagonist. Thus coronary aspirate from stented nRCA is characterized by less debris but more endothelin and stronger vasoconstrictor response than that from SVG-RCA. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis is the primary cause of coronary heart disease (CHD), preceding the onset of cardiovascular disease by decades in most cases. Here we examine the association between single nucleotide polymorphisms (SNPs) integrated on Metabochip and coronary artery calcification (CAC), a valid risk factor for CHD, in an unselected, population-based German cohort. Methods: The Metabochip is a custom iSELECT array containing >195,000 SNPs that was designed to support large-scale follow-up of putative associations for metabolic and cardiovascular-associated traits. We used generalized linear regression models to explore the impact of Metabochip SNPs on quantitative CAC in 4,329 participants. Results: The 9p21 variant, rs1537373, was most strongly associated (Beta = 0.30; 95% confidence interval (CI) = 0.21-0.39; p = 4.05x10-11) with quantitative CAC. The second strongest association with CAC was with rs9349379 in the phosphatase and actin regulator 1 gene, PHACTR1, (Beta = 0.30; 95% CI = 0.22-0.40; p = 4.67x10-11). Both SNPs remained nominally significant in dichotomized analyses for the presence of any CAC (odds ratiors1537373 (OR) = 1.19; 95% CI = 1.07-1.31; p = 0.001 and ORrs9349379 = 1.26; 95% CI = 1.14-1.40); p = 1.5×10-5). Fine mapping of the 9p21 and PHACTR1 gene region revealed several other SNPs that were strongly associated with CAC. Conclusion: We demonstrate that SNPs near 9p21 and in PHACTR1 that have previously been shown to be associated with CHD are strongly associated with CAC in the Heinz Nixdorf Recall Study cohort. Our findings suggest that the 9p21 and 6q24 loci might be involved in cardiac outcome via promoting development of atherosclerosis in the coronary arteries. [ABSTRACT FROM AUTHOR]

Background: Secondhand smoke (SHS) consists of fine particulate matter, carcinogens, and various toxins that affect large parts of the population. SHS increases the risk for acute cardiovascular events and may contribute to the development of atherosclerosis. Objectives: We investigated the association of SHS with coronary artery calcification (CAC). Methods: In this cross-sectional analysis, we used baseline data (2000-2003) from 1,766 never-smokers without clinically manifested coronary heart disease, 45-75 years of age, from the Heinz Nixdorf Recall Study, an ongoing, prospective, population-based cohort study in Germany. Self-reported frequent SHS at home, at work, and in other places was assessed by questionnaire. CAC scores were derived based on electron-beam computed tomography. We conducted multiple linear regression analysis using exposure to SHS as the explanatory variable and In(CAC+1) as the response variable. We conducted logistic regression to estimate the odds ratio (OR) for presence of any CAC. Results: Frequent exposure to SHS was reported by 21.5% of participants. After adjustment forage, sex, and socioeconomic status, CAC + 1 was 21.1% [95% confidence interval (CI): -5.5%, 55.2%] higher in exposed than in unexposed participants. After adjusting for other cardiovascular risk factors, the association was attenuated (15.4%; 95% CI: -9.6%, 47.2%). SHS exposure was also associated with a CAC score > 0 (fully adjusted OR = 1.38; 95% CI: 1.03, 1.84). Conclusions: Self-reported frequent exposure to SHS was associated with subclinical coronary atherosclerosis in our cross-sectional study population. Considering the widespread exposure and the clinical relevance of coronary atherosclerosis, this result, if confirmed, is of public health importance. [ABSTRACT FROM AUTHOR]

The article presents a study which aimed to quantify the release of vasoconstrictors during stent implantation into atherosclerotic plaques and to determine the efficacy of coronary dilators to attenuate their action. Results showed serotonin as the main coronary vasoconstrictor released after stenting with thromboxane and tumor necrosis factor (TNF)α potentiating the response. Nitroprusside and verapamil were found to be more potent than adenosine in attenuating the aspirate plasma-induced vasoconstriction.

Background: The value of assessing coronary artery calcium (CAC) with regard to characterizing unstable coronary artery disease remains controversial. Purpose: To evaluate the amount of CAC in patients with an acute marker-positive coronary syndrome in segments containing the culprit lesion compared with the remote coronary segments. Material and Methods: Thirty-two patients with a marker-positive acute coronary syndrome were examined using electron-beam computed tomography (EBCT), selective coronary angiography and, in some, intravascular ultrasound. The coronary anatomy was analyzed according to the segmental classification proposed by the American Heart Association (AHA). Results: The total EBCT coronary artery calcium score (CAC, Agatston method) was 251±371 (range 0-1629). In 81% of the patients, a greater CAC score was observed than expected on the basis of age and gender. In 30 patients, significant stenoses were detected. The CAC score of the culprit vessel was 108±163 vs 78±134 in the non-culprit vessels and did not differ significantly (P=0.4). The mean CAC score of the coronary segment (AHA classification) containing the culprit lesion was 51±82 vs 29±45 in the other coronary artery segments (P=0.14). Of the two patients with no CAC detected by EBCT, one had no coronary atherosclerosis (confirmed by intravascular ultrasound) and one had one vessel coronary artery disease. Conclusion: Coronary calcium related to the culprit lesion in patients with a marker-positive acute coronary syndrome showed a tendency for an increased amount but was not statistically different from the amount of coronary calcium in remote vessel segments. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Inhabitants of deprived neighbourhoods are at higher risk of coronary heart disease. In this study we investigate the hypothesis that social inequalities at neighbourhood level become already manifest in subclinical coronary atherosclerosis, as defined by electron-beam computed tomography derived measures. Coronary artery calcification was assessed as a marker of atherosclerosis in a population based sample of 4301 men and women (45–75 years) without a history of coronary heart disease. Participants lived in three adjacent cities in Germany and were examined between 2000 and 2003 as part of the Heinz Nixdorf Recall Study. Individual level data was combined with neighbourhood level information about unemployment, welfare and living space per inhabitant. This dataset was analysed with descriptive and multilevel regression methods. An association between neighbourhood deprivation and subclinical coronary calcification was observed. After adjustment for age and individual socioeconomic status male inhabitants of high unemployment neighbourhoods had an odds ratio of 1.45 (1.11, 1.96) of exhibiting a high calcification score (>75th percentile) compared to men living in low unemployment areas. The respective odds for women was 1.29 (0.97, 1.70). Additional explorative analyses suggest that clustering of unhealthy lifestyles in deprived neighbourhoods contributes to the observed association. In conclusion, findings suggest that certain neighbourhood characteristics promote the emergence of coronary atherosclerosis. This might point to a pathway from neighbourhood deprivation to manifest coronary heart disease. [ABSTRACT FROM AUTHOR]

The article focuses on the significance of non-invasive screening for coronary artery disease. The incidence of sudden cardiac death (SCD) in patients with known risk of SCD is in the region of 30% annually. The use of algorithms provided by the international and national societies as a first step was recommended for individual risk assessment. Fluoroscopy allows the detection of calcification of the coronary arteries.

Abstract: 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 (≥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. [Copyright &y& Elsevier]

Objective The C825T polymorphism of the gene encoding the human G protein beta-3 subunit ( GNB3 ) is associated with hypertension and obesity. Moreover, genotypes of the GNB3 polymorphism have been associated with development of coronary artery disease, and the 825T allele is thought to influence the process of atherosclerosis. However, the potential of the C825T polymorphism to predict coronary events has been poorly explored in a longitudinal setting at the population level. Methods In 4159 Caucasian subjects from the Heinz Nixdorf Recall study cohort (age: 45–75 years, 48% male), genotypes of the GNB3 C825T polymorphism (rs5443) were determined and associated with fatal and non-fatal myocardial infarction (hard coronary events). Established cardiovascular risk factors were used to adjust for confounders. Results The median follow-up time was 9.9 years (1st/3rd quartiles 9.5/10.2). 148 subjects (3.6%) experienced a hard coronary event. The 10-year event-free survival rate was CC, 96.1%; CT 96.9%, TT, 93.7% ( p = 0.018). Multivariable analysis showed that the TT genotype is a significant risk factor for hard coronary events (hazard ratio (HR) = 1.9 (95% confidence interval (CI) 1.2–2.9); p = 0.008) after adjustment for age, sex, diabetes, systolic blood pressure, body mass index, high-density lipoprotein, and coronary artery calcification as determined by electron beam computed tomography at baseline. While prognosis in females was independent of GNB3 genotypes, analysis in males even elevated the HR for TT versus C-allele to 2.6 (95% CI 1.6–4.2; p < 0.001). Conclusion The GNB3 825 TT genotype is a significant and independent risk factor for hard coronary events independent of other established cardiovascular risk factors at a population level in males. [ABSTRACT FROM AUTHOR]

Background: Computed tomography (CT) allows estimation of coronary artery calcium (CAC) progression. We evaluated several progression algorithms in our unselected, population-based cohort for risk prediction of coronary and cardiovascular events.Methods: In 3281 participants (45-74 years of age), free from cardiovascular disease until the second visit, risk factors, and CTs at baseline (b) and after a mean of 5.1 years (5y) were measured. Hard coronary and cardiovascular events, and total cardiovascular events including revascularization, as well, were recorded during a follow-up time of 7.8±2.2 years after the second CT. The added predictive value of 10 CAC progression algorithms on top of risk factors including baseline CAC was evaluated by using survival analysis, C-statistics, net reclassification improvement, and integrated discrimination index. A subgroup analysis of risk in CAC categories was performed.Results: We observed 85 (2.6%) hard coronary, 161 (4.9%) hard cardiovascular, and 241 (7.3%) total cardiovascular events. Absolute CAC progression was higher with versus without subsequent coronary events (median, 115 [Q1-Q3, 23-360] versus 8 [0-83], P<0.0001; similar for hard/total cardiovascular events). Some progression algorithms added to the predictive value of baseline CT and risk assessment in terms of C-statistic or integrated discrimination index, especially for total cardiovascular events. However, CAC progression did not improve models including CAC5y and 5-year risk factors. An excellent prognosis was found for 921 participants with double-zero CACb=CAC5y=0 (10-year coronary and hard/total cardiovascular risk: 1.4%, 2.0%, and 2.8%), which was for participants with incident CAC 1.8%, 3.8%, and 6.6%, respectively. When CACb progressed from 1 to 399 to CAC5y≥400, coronary and total cardiovascular risk were nearly 2-fold in comparison with subjects who remained below CAC5y=400. Participants with CACb≥400 had high rates of hard coronary and hard/total cardiovascular events (10-year risk: 12.0%, 13.5%, and 30.9%, respectively).Conclusions: CAC progression is associated with coronary and cardiovascular event rates, but adds only weakly to risk prediction. What counts is the most recent CAC value and risk factor assessment. Therefore, a repeat scan >5 years after the first scan may be of additional value, except when a double-zero CT scan is present or when the subjects are already at high risk. [ABSTRACT FROM AUTHOR]

Background B-type natriuretic peptide (BNP) as well as N-terminal-proBNP (NT-proBNP) are associated with cardiac events in the general population. Yet, data from the general population comparing both peptides for their prognostic value is lacking. Methods Participants from the population-based Heinz-Nixdorf-Recall-study without cardiovascular diseases were included. Associations of BNP and NT-proBNP with incident cardiovascular events (incident myocardial infarction, stroke, or cardiovascular death) were assessed using Cox regression; prognostic value was addressed using Harrell's c statistic. Results From overall 3589 subjects (mean age: 59.3 ± 7.7 yrs, 52.5% female), 235 subjects developed a cardiovascular event during 8.9 ± 2.2 yrs of follow-up. In regression analysis both natriuretic peptides were associated with incident cardiovascular events, independent of traditional risk factors (hazard ratio (HR) per unit increase on log-scale (95% CI): NT-proBNP: 1.60 (1.39; 1.84); BNP: 1.37 (1.19; 1.58), p < 0.0001 respectively). Specifically looking at subjects < 60 yrs only NT-proBNP, was linked with events (HR (95% CI): 1.59 (1.19; 2.13) for NT-proBNP, p = 0.0019; HR: 1.25 (0.94; 1.65) for BNP, p = 0.12, after adjustment for age and gender). Similar results were observed for females (HR (95% CI) 1.65 (1.28; 2.12), p = 0.0001 for NT-proBNP, and 1.24 (0.96; 1.61), p = 0.10 for BNP after adjustment for age). Adding NT-proBNP/BNP to traditional risk factors increased the prognostic value, with effects being stronger for NT-proBNP (Harrell's c, 0.724 to 0.741, p = 0.034) as compared to BNP (0.724 to 0.732, p = 0.20). Conclusion Both, NT-proBNP and BNP are associated with future cardiovascular events in the general population. However, when both are available, NT-proBNP seems to be superior due to its higher prognostic value, especially in younger subjects and females. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]