The association between liver fat and systemic calcified atherosclerosis.

BACKGROUND: The association of nonalcoholic fatty liver disease (NAFLD) with systemic calcified atherosclerosis, other than the coronary arteries, has not been clearly elucidated. We investigated the association between NAFLD and calcification in eight different vascular beds. METHODS: In a community-based cohort with computed tomography scans for carotid artery, coronary artery, thoracic aorta, abdominal aorta, iliac artery, renal artery, celiac trunk, and superior mesenteric artery, the association between NAFLD and arterial calcification was evaluated with adjustment for age, sex, hypertension, dyslipidemia, diabetes, obesity, current smoking status, and family history of heart disease in the first-degree relatives. RESULTS: In age- and sex-adjusted models, NAFLD was significantly associated with calcification in the coronary artery, carotid artery, thoracic aorta, celiac trunk, and superior mesenteric artery vascular beds (P < .05). However, adjustment for the traditional chronic venous disease risk factors attenuated the associations, except in the case of the thoracic aorta (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.09-1.78) and celiac trunk (OR, 2.05; 95% CI, 1.16-3.65). In addition, NAFLD was independently associated with multiarterial calcification (four or more [OR, 1.33; 95% CI, 1.01-1.74], five or more [OR, 1.46; 95% CI, 1.09-1.97], and six or more [OR, 1.58; 95% CI, 1.09-2.30] of eight evaluated arterial segments). CONCLUSIONS: The association between NAFLD and arterial calcification is mainly mediated by conventional risk factors. The independent association between NAFLD and calcification in the thoracic aorta and celiac trunk as well as in a larger number of vascular beds needs confirmation in future prospective studies in diverse populations.

Superior mesenteric artery calcification is associated with cardiovascular risk factors, systemic calcified atherosclerosis, and increased mortality.

BACKGROUND: Atherosclerosis is a major risk factor for morbidity and mortality. However, epidemiologic data are sparse regarding risk factors for superior mesenteric artery calcification (SMAC), the association between SMAC and disease in other arterial beds, or the independent contribution of SMAC to risk of mortality. The objective of this study was to test the hypothesis that presence and extent of SMAC are associated with cardiovascular disease (CVD) risk factors, calcification in other arterial beds, and both cardiovascular and all-cause mortality, independent of classic risk factors and calcification in other arterial beds. METHODS: Arterial calcification in the superior mesenteric artery, celiac trunk, coronaries, thoracic aorta, abdominal aorta, and iliac arteries was evaluated by computed tomography in adults with no known CVD. Multiple logistic regression models examined risk factor associations for SMAC and SMAC as a risk factor for calcification in other arterial beds. Cox models were used to examine the association between SMAC and mortality. RESULTS: The average age of subjects was 56 years; 43.7% (1877/4300) were women, and 6.7% (290) had SMAC. Age (odds ratio [OR], 1.09; 95% confidence interval, 1.06-1.11), male sex (OR, 1.79; 95% CI, 1.08-3.03), dyslipidemia (OR, 1.38; 95% CI, 1.01-1.88), and any smoking (OR, 1.60; 95% CI, 1.20-2.14) were associated with SMAC presence. Notably, body mass index, body fat percentage, hypertension, diabetes, and family history of coronary heart disease were not significant risk factors for the presence of SMAC. SMAC presence was associated with calcification in all five other arterial beds (OR, 6.02; 95% CI, 3.76-9.66). During a median follow-up time of 9.4 years, there were 234 deaths, 76 of which were CVD related. SMAC extent (represented as per-unit increase in log [SMAC score + 1]; OR, 1.31; 95% CI, 1.01-1.71) was significantly associated with CVD mortality after full adjustment for risk factors and calcification in other arterial beds. SMAC presence (OR, 1.52; 95% CI, 1.10-2.12) and extent (OR, 1.25; 95% CI, 1.06-1.48) were also both significantly associated with all-cause mortality after full adjustment. CONCLUSIONS: SMAC is associated with specific CVD risk factors as well as with calcification in all other arterial beds. SMAC extent was significantly associated with incident cardiovascular mortality, whereas both SMAC presence and extent were significantly associated with all-cause mortality, even after adjustment for risk factors and calcification in other arterial beds. Further studies are needed to determine whether SMAC is simply a marker for advanced and systemic disease or whether it confers increased mortality risk through an independent mechanism.

Calcified atherosclerosis in different vascular beds and the risk of mortality.

OBJECTIVE: The goal of this study was to determine differences in risks for total and cause-specific mortality related to calcified atherosclerosis in different vascular beds. METHODS AND RESULTS: A total of 4544 patients underwent computed tomography scans that were interrogated for calcium in different vascular beds. Mortality assessment was conducted by death certificate adjudication. At baseline, the mean age was 56.8 years, and 43% were female. After an average of 7.8 years, there were 163 deaths. With full adjustment, the presence of calcium in the thoracic aorta (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.2-3.5), carotids (HR, 1.60; CI, 1.1-2.5), and iliac (HR, 1.67; CI, 1.0-2.9) arteries were associated with total mortality, whereas the presence of coronary calcium was associated with cardiovascular disease (CVD) mortality (HR, 3.4; CI, 0.8-10.9). For severity of calcium burden, a 1-SD increment in the iliac arteries was the strongest predictor for all types of mortality. C-statistics were not significantly larger when noncoronary vascular beds were added to models with CVD risk factors or CVD risk factors plus coronary artery calcium. CONCLUSIONS: The associations between calcified atherosclerosis and mortality differ by vascular bed, suggesting that the location and severity of calcification in different vascular beds provide unique information for mortality.

Health behavior modification after electron beam computed tomography and physician consultation.

This study aimed to determine whether participants reported altering health behaviors (physical activity, diet, and alcohol consumption) after seeing results from an electron-beam computed tomography (EBCT) scan for coronary artery calcium and reviewing these results with a physician. Clinicians attempt to motivate patients to control cardiovascular risk factors by adopting healthy behaviors and reducing harmful actions. Asymptomatic patients (N = 510) were evaluated by EBCT for the extent of coronary artery calcium. Information pertaining to demographics, health history, and lifestyle/health behaviors was obtained from each participant at the time of the EBCT scan. Patients were given their numerical calcium score, shown images of their coronary arteries, and counseled by a physician for lifestyle and medical risk modification based on their coronary artery calcium score. Approximately 6 years after the scan, participants completed a follow-up questionnaire related to lifestyle modifications. In multivariable analysis, the presence and extent of coronary artery calcium was significantly associated with beneficial health behavior modifications. Specifically, the greater a patient's coronary artery calcium score, the more likely they were to report increasing exercise (odds ratio = 1.34, P = 0.02), changing diet (odds ratio = 1.40, P < 0.01), and changing alcohol intake (odds ratio = 1.46, P = 0.05). This study suggests that seeing and being counseled on the presence and extent of coronary artery calcium is significantly associated with behavior change.

Associations of Perirenal Fat Thickness with Renal and Systemic Calcified Atherosclerosis.

BACKGROUND: We investigated associations between perirenal fat thickness and atherosclerotic calcification in six different vascular beds. METHODS: Using a community-based cohort (n=3,919), perirenal fat thickness was estimated from computed tomography scans. It was classified as Q1 (the lowest quartile) to Q4 (the highest quartile) in each sex. Calcification in the carotid arteries, coronary arteries, thoracic aorta, abdominal aorta, iliac arteries, and renal arteries was evaluated. RESULTS: Perirenal fat thickness was associated with older age (P<0.01) and a higher prevalence of obesity, hypertension, and dyslipidemia (P<0.01 for all). Perirenal fat thickness was independently associated with renal arterial calcification even after adjustment for age, sex, body mass index, hypertension, dyslipidemia, smoking history, and family history of heart diseases in first-degree relatives (odds ratio [OR] per quartile of perirenal fat thickness, 1.25; 95% confidence interval [CI], 1.09 to 1.44). Compared to Q1, the odds of renal arterial calcification in Q4 was about two times higher (OR, 2.05; 95% CI, 1.29 to 3.25). After adjustment for renal arterial calcification and atherosclerotic risk factors, the only other vascular bed where perirenal fat thickness showed a significant association with calcification was the abdominal aorta (OR, 1.11; 95% CI, 1.00 to 1.23; P=0.045). CONCLUSION: Perirenal fat thickness was independently associated with vascular calcification in the renal artery and abdominal aorta.

Mitral and aortic annular calcification are highly associated with systemic calcified atherosclerosis.

BACKGROUND: Atherosclerosis has been implicated as a cause of valvular calcification. The aim of this study was to determine whether atherosclerotic calcification in multiple vascular areas is significantly associated with aortic or mitral annular calcification independent of traditional risk factors. METHODS AND RESULTS: A total of 1242 consecutive asymptomatic patients free of clinical coronary heart disease were studied by electron-beam computed tomography for the extent of calcium due to atherosclerosis in 5 distinct vascular beds and calcium in the aortic and mitral annuli. Nearly 24% had calcium in the aortic annulus, whereas 8% were found to have mitral annular calcification. Age and a history of hypertension were the only traditional cardiovascular risk factors that were independently associated with prevalent calcification in the aortic and mitral annuli. After adjustment for age, gender, and cardiovascular disease risk factors, subjects with calcium in the thoracic aorta had the highest odds for the presence of aortic annular calcium (OR=3.9, P<0.01), whereas those with calcium in the abdominal aorta had the highest odds for mitral annular calcification (OR=5.1, P=0.01). Standardized increases in calcium in the abdominal aorta (OR=2.0, P<0.01) and iliacs (OR=1.8, P=0.01) were significantly associated with calcium in the aortic annulus after adjustment for the extent of calcium in the other vascular beds, whereas the thoracic aorta was significantly associated (OR=1.4, P=0.02) with calcium in the mitral annulus. CONCLUSIONS: This study supports the hypothesis that calcification of the mitral and aortic annuli is related to atherosclerosis in other vascular beds.

Calcification of the splenic, iliac, and breast arteries and risk of all-cause and cardiovascular mortality.

BACKGROUND AND AIMS: CVD risks associated with coronary artery calcification (CAC) and aortic calcification (AC) are well known, but less is known about other calcified arteries. We aimed to assess the associations of arterial calcification in the breast, splenic, and internal and external iliac arteries with CVD risk factors and mortality. METHODS: We conducted a case-cohort study nested in a cohort of 5196 individuals who self-referred or were referred by a health care provider for whole body computed tomography (CT), including a random subcohort (n = 395) and total and CVD mortality cases (n = 298 and n = 90), who died during a median follow-up of 9.4 years. Arterial calcification in the breast, splenic, and internal and external iliac arteries on CT was scored using a simple visual score. AC and CAC were previously measured using the Agatston technique. Logistic regression models were made to study associations of CVD risk factors with calcification in the different vascular beds. Prentice-weighted Cox proportional hazards models adjusted for CVD risk factors, and calcification in other vascular beds, were used to study associations with mortality. RESULTS: In the subcohort, the mean age was 56.6 years (SD 11.1) and 41.3% were female. The prevalence of calcification on CT, was 11.6% in the splenic, 47.9% in the internal iliac and 9.5% in the external iliac arteries, while 3.7% of women had breast artery calcification (BAC). Calcification in the splenic and iliac arteries was associated with calcification in the abdominal aorta but differentially associated with other CVD risk factors in logistic regression models. The prevalence of BAC was too low to fit these multivariable models. Calcification of the external iliac arteries was significantly associated with both all-cause and CVD mortality, but no longer significant when adjusted for CVD risk factors. Breast artery calcification was associated with both all-cause and CVD mortality independent of CVD risk factors and AAC and CAC (all-cause HR 5.67 [95% CI 1.50-21.41]). CONCLUSIONS: Risk factors associated with calcification, and the association of calcification with risk of mortality differ across vascular beds, possibly reflecting different pathophysiology.

Relationship of Coronary Calcium on Standard Chest CT Scans With Mortality.

OBJECTIVES: The aim of this study was to determine the correlation between coronary artery calcium (CAC) scores on 3 mm electrocardiography (ECG)-gated computed tomography (CT) scans and standard 6 mm chest CT scans, and to compare relative strength of associations of CAC on each scan type with mortality risk. BACKGROUND: Coronary artery calcification predicts cardiovascular disease (CVD) and all-cause mortality, and is typically measured on ECG-gated 3 mm CT scans. Patients undergo standard 6 mm chest CTs for various clinical indications much more frequently, but CAC is not usually quantified. To better understand the usefulness of standard chest CTs to quantify CAC, we conducted a case-control study among persons who had both scan types. METHODS: Between 2000 and 2003, 4,544 community-living individuals self- or physician-referred for "whole-body" CT scans, had 3 mm ECG-gated CTs and standard 6 mm chest CTs, and were followed for mortality through 2009. In this nested case-control study, we identified 157 deaths and 494 controls frequency matched (1:3) on age and sex. The Agatston method quantified CAC on both scan types. Unconditional logistic regression determined associations with mortality, accounting for CVD risk factors. RESULTS: Participants were 68 ± 11 years of age and 63% male. The Spearman correlation of CAC scores between the 2 scan types was 0.93 (p < 0.001); median CAC scores were lower on 6 mm CTs compared to 3 mm CTs (22 vs.104 Agatston units, p < 0.001). Adjusted for traditional CVD risk factors, each standard deviation higher CAC score on 6 mm CTs was associated with 50% higher odds of death (odds ratio: 1.5; 95% confidence interval: 1.2 to 1.9), similar to 50% higher odds on the 3 mm ECG-gated CTs (odds ratio: 1.5; 95% confidence interval: 1.1 to 1.9). CONCLUSIONS: CAC scores on standard 6 mm chest CTs are strongly correlated with 3 mm ECG-gated CTs and similarly predict mortality in community-living individuals. Chest CTs performed for other clinical indications may provide an untapped resource to garner CVD risk information without additional radiation exposure or expense.

Patterns and risk factors for systemic calcified atherosclerosis.

OBJECTIVE: Complex atherosclerotic lesions contain radio-opaque calcium hydroxyapatite deposits with the degree of calcification correlating with the extent of atherosclerosis. In this study, we aim to determine the patterns of systemic atherosclerotic calcification. METHODS AND RESULTS: Whole-body electron beam computed tomography scans were performed on 650 asymptomatic subjects to assess the carotid, coronary, proximal, and distal aorta and iliac vessels for atherosclerotic calcification. The mean age was 57.3 and 53% were male. Correlation patterns were similar in both genders, with the largest interbed correlations between the distal aorta and iliac vessels (r=0.51 to 0.60). The average man and woman had calcium earliest in the coronaries (younger than age 50 years) and the distal aorta (age 50 to 60), respectively. The prevalence of calcium was greater than 80% for most beds in men older than age 70 and greater than 60% in all beds for women. Approximately on third of subjects younger than 50 were free of calcified disease, whereas all subjects older than 70 were found to have some calcium. Age and hypertension were the dominant risk factors for systemic calcified atherosclerosis. CONCLUSIONS: This study confirms that there are significant correlations and risk factor associations for calcified atherosclerosis in different vascular beds.

Age and gender are the strongest clinical correlates of prevalent coronary calcification (R1).

OBJECTIVE: To determine which of the standard cardiovascular risk factors have the strongest associations with prevalent coronary artery calcification (CAC). STUDY DESIGN AND SETTING: A cross-sectional study of 6086 consecutive subjects who underwent electron beam computed tomography for CAC at a private, university-affiliated disease prevention center in San Diego, CA. RESULTS: The correlation between age and coronary calcium score in men (r=0.463) was twice that of the next highest correlation (0.218) for percent body fat. A similar relationship was found for women (0.413 vs. 0.238). Calcium scores increased incrementally by age category in both men and women. This pattern of increase was not present for LDL cholesterol. Men and women over the age of 74 had highly elevated risks for the presence of any calcified coronary atherosclerosis compared to those under the age of 45 (OR [95% CI]: 11.08 [6.186-19.859] and 11.81 [6.718-20.746], respectively). Addition of the other traditional cardiovascular risk factors did not significantly increase the discriminatory power beyond that provided by age on ROC analysis. CONCLUSION: Age and gender are significant independent clinical correlates of coronary calcium beyond that provided by the other risk factors. These results support the hypothesis that age is the predominant risk factor for coronary calcification.

Atherosclerotic calcification and intimal medial thickness of the carotid arteries.

BACKGROUND AND PURPOSE: Carotid intimal medial thickness (IMT) is a measure of subclinical atherosclerosis and is predictive of future cardiovascular events. The purpose of this study was to determine the significance and magnitude of association between IMT and atherosclerotic calcification of the carotid arteries. METHODS: Forty-five subjects underwent electron beam computed tomography of the neck to ascertain the extent of atherosclerotic calcification in the carotid arteries followed by B-mode carotid ultrasonography for IMT. RESULTS: The mean age, BMI and total cholesterol to HDL ratio were 61.4, 26.2 and 4.3, respectively. Forty-one percent were women. The overall mean IMT was 0.91 mm with the mean for the right and left being 0.93 and 0.87 mm, respectively. The median total carotid calcium score (CCS) was 48.4 [range: 0-973]. Age-adjusted correlations were significant between the overall mean IMT and total CCS (r=0.53, p<0.01), mean right IMT and right CCS (0.31, 0.05), mean left IMT and left CCS (0.31, 0.05), right common carotid IMT and right CCS (0.53, <0.01) and left common carotid IMT and left CCS (0.31, 0.05). The mean IMT was 0.14 mm greater in subjects with any carotid calcification adjusted for risk factors. A 0.05 mm increase in the carotid IMT was associated with an approximate 3-fold increase in risk for the presence of atherosclerotic calcification. CONCLUSIONS: Carotid IMT is significantly correlated with and predictive of atherosclerotic calcification. Conversely, individuals with any carotid calcification have significantly greater intimal medial thicknesses.

A comparison of HDL and LDL cholesterol for prevalent coronary calcification.

BACKGROUND: Coronary calcification is a marker for coronary atherosclerosis. It has been postulated that high levels of high density lipoprotein cholesterol (HDL-C) are associated with a reduced amount of atherosclerotic disease while previous reports have found a lack of association between low density lipoprotein cholesterol (LDL-C) and coronary calcification (CAC). The purpose of this study was to compare the correlation and predictive power of HDL-C with LDL-C for prevalent coronary calcification. METHODS: A total of 6093 subjects were studied with respect to coronary calcification, serum cholesterol indices, personal health history and body morphology. Analyses consisted of correlation coefficients, logistic regression and sensitivity analysis to determine the strength of association between HDL-C and coronary calcification after controlling for covariates. RESULTS: The correlation between HDL-C and coronary calcium score (CCS) was three times that of LDL-C. Individuals with an HDL-C level <40 mg/dl had significantly higher calcium scores while increases in HDL-C were associated with a significant reduction in risk for the presence of any calcified plaque. Results of multivariate logistic regression revealed that HDL-C is predictive of calcified plaque development independent of LDL-C. Sensitivities and positive predictive values for both HDL-C and LDL-C were low. CONCLUSIONS: Increasing levels of HDL-C were associated with less coronary calcification and a smaller probability of having any calcified disease supporting the antiatherogenic hypothesis for HDL-C. HDL-C predicts the presence of any calcified atherosclerotic plaque independently of LDL-C. However, neither parameter seems suitable as a screening tool for predicting prevalent calcified atheromatous disease.

Comparison of ordinal versus Agatston coronary calcification scoring for cardiovascular disease mortality in community-living individuals.

Coronary artery calcification (CAC) by the Agatston method predicts cardiovascular disease (CVD), but requires cardiac gated computed tomography (CT) scans, a procedure not covered by most insurance providers. An ordinal CAC score (scored 0-12 based on artery number and extent of calcification involvement) can be measured on standard chest CTs. However, the correlation of ordinal and Agatston CAC scores and their relative association with CVD mortality is uncertain, which we sought to determine. Nested case-control study. Community-living individuals undergoing "whole body" CT scans for preventive medicine. 4,544 consecutive patients with CT scans, were followed from 2000 to 2009. We selected cases who died of CVD (n = 57) and age, sex, and CT slice-thickness matched each case to three controls (N = 171). Cardiac gated 3 mm chest CTs and non-gated 6 mm standard chest CTs. CVD death over 9 years follow-up. The intra- and inter-reader kappa for the ordinal CAC score was 0.90 and 0.76 respectively. The correlation of Agatston and ordinal CAC scores was 0.72 (p < 0.001). In models adjusted for traditional CVD risk factors, the odds of CVD death per 1 SD greater CAC was 1.66 (1.03-2.68) using the ordinal CAC score and 1.57 (1.00-2.46) using the Agatston score. A simple ordinal CAC score is reproducible, strongly correlated with Agatston CAC scores, and provides similar prediction for CVD death in predominantly Caucasian community-living individuals.

Influence of patients' coronary artery calcium on subsequent medication use patterns.

OBJECTIVES: To determine whether information on the presence and extent of coronary artery calcium (CAC) is associated with the likelihood of physicians' prescribing preventive therapies. METHOD: In a longitudinal design, asymptomatic participants (N=510) were evaluated by computed tomography for CAC. Changes to medications were at the discretion of the patient's primary care provider, who received the CT report. RESULTS: In multivariable analysis, the likelihood of patients reporting that their primary care physician prescribed preventive therapies was significantly associated with the presence and extent of CAC. CONCLUSIONS: This study suggests that physicians' prescribing practices are influenced by patients' CAC scores obtained via CT.

Biographical notes on Ancel Keys and Salim Yusuf: origins and significance of the seven countries study and the INTERHEART study.

Ancel Keys and Salim Yusuf are both pioneers in preventive cardiology. Each overcame significant obstacles to demonstrate, through large international studies, how culture and environment influence cardiovascular disease. This paper will explore the origins and outcomes of their landmark studies: the Seven Countries Study, a prospective cohort model, and the INTERHEART Study, a case-control model. Each study advanced our understanding of the interplay between lifestyle, culture, and heart disease.

The association between abdominal body composition and vascular calcification.

Subclinical cardiovascular disease (CVD) may be associated with both adipose and skeletal muscle tissues in the abdomen. Accordingly, we examined whether subcutaneous, intermuscular, and visceral adipose tissue, as well as abdominal lean muscle, were associated with the presence and extent of vascular calcification in multiple vascular beds. Three hundred and ninety four patients (58.1% men) underwent electron beam computed tomography (EBCT) scans as part of routine health maintenance screening. The coronary and carotid calcium scores were analyzed at the time of the scan, whereas the other calcium scores, as well as the body composition analyses, were analyzed retrospectively. Mean age was 55.2 ± 11.1 years and BMI was 26.9 ± 4.2. The prevalence of any calcification in the carotids, coronaries, thoracic aorta, abdominal aorta, and iliacs was 30.1, 60.1, 39.8, 55.7, and 56.8%, respectively. Compared to those with calcification in different vascular beds, those without vascular calcification generally had significantly more lean muscle and less adipose tissue. In separate multivariable logistic models, a 1 s.d. increment in the ratio of abdominal and visceral fat to total area of each corresponding compartments was significantly associated with an increased odds for the presence of thoracic aortic calcium (odds ratio (OR) = 1.6, 1.5, respectively; P = 0.01 for both). Conversely, increases in abdominal lean muscle were associated with significantly decreased odds of thoracic aortic calcification (OR = 0.34; P ≤ 0.01). A similar pattern of associations existed among the other vascular beds. Also, the association between lean muscle and vascular calcification was independent of visceral adipose tissue. In conclusion, adipose tissue was positively and lean body mass inversely associated with prevalent aortic calcification.