Mitral and aortic valve sclerosis/calcification and carotid atherosclerosis: results from 1065 patients

This study assesses whether aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are associated with carotid artery atherosclerosis, independently of traditional cardiovascular risk factors. A total of 1065 patients underwent both echocardiography and carotid artery ultrasound scanning. AVS and MAC were defined as focal areas of increased echogenicity and thickening of the aortic leaflets or mitral valve annulus. Carotid artery atherosclerosis was defined as presence/absence of any atherosclerotic plaque or presence/absence of plaque >50 %. Of 1065 patients (65 ± 9 years; 38 % female) who comprised the study population, 642 (60 %) had at least one atherosclerotic plaque. AVS, but not mitral valve sclerosis; was associated with the presence of carotid atherosclerosis (odds ratio (OR) 1.9, 95 % confidence interval (CI) 1.2–3.9; P = 0.005) and the degree of carotid atherosclerosis (OR 2.1, 95 % CI 1.2–3.9; P = 0.01) in a multivariate model including age, gender, previous ischemic heart disease, hypertension, dyslipidemia, smoking, diabetes, family cardiovascular history, left ventricular size, mass, and ejection fraction, and left atrial size. AVS is a significant predictor of carotid atherosclerosis, independently of other cardiovascular clinical and echocardiographic risk factors.     

Relation of coronary artery disease and cerebrovascular disease with atherosclerosis of the thoracic aorta in the general population.

The association between clinical coronary artery disease, cerebrovascular disease, and aortic atherosclerosis has not been examined in the general population. Transesophageal echocardiography was performed in 581 subjects, a random sample of the Olmsted County (Minnesota) population aged >/=45 years, participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. The frequency and severity of atherosclerosis of the thoracic aorta were determined in the population and the association between clinical coronary artery disease, cerebrovascular disease, and aortic atherosclerosis was examined. Previous myocardial infarction, angina pectoris, and coronary artery bypass surgery were significantly associated with aortic atherosclerosis, adjusting for age and gender (p 4-mm thick, ulcerated plaques, or mobile debris), adjusting for age and gender (p <0.05). Age, smoking, pulse pressure, previous myocardial infarction (odds ratio [OR] 4.67; 95% confidence interval [CI] 1.42 to 15.40), and coronary artery bypass surgery (OR 5.12; 95% CI 1.01 to 26.01) were independently associated with aortic atherosclerosis. Among subjects with atherosclerosis, age, smoking, pulse pressure, hypertension treatment, and coronary artery disease (OR 2.50; 95% CI 1.18 to 5.30) were independently associated with complex atherosclerosis. Weak associations were observed between previous ischemic stroke, transient ischemic attack, and aortic atherosclerosis, associations that were not significant after age- and gender-adjustment (p >0.2). Thus, coronary artery disease is strongly associated with aortic atherosclerosis and complex atherosclerosis in the general population. Cerebrovascular disease is weakly associated with aortic atherosclerosis, thereby questioning the overall importance of aortic atherosclerosis in the pathogenesis of cerebrovascular events in the general population.     

Post-traumatic stress disorder, coronary atherosclerosis, and mortality

Post-traumatic stress disorder (PTSD) is associated with increased risk of multiple medical problems including myocardial infarction. However, a direct link between PTSD and atherosclerotic coronary artery disease (CAD) has not been made. Coronary artery calcium (CAC) score is an excellent method to detect atherosclerosis. This study investigated the association of PTSD to atherosclerotic CAD and mortality. Six hundred thirty-seven veterans without known CAD (61 ± 9 years of age, 12.2% women) underwent CAC scanning for clinical indications and their psychological health status (PTSD vs non-PTSD) was evaluated. In subjects with PTSD, CAC was more prevalent than in the non-PTSD cohort (76.1% vs 59%, p = 0.001) and their CAC scores were significantly higher in each Framingham risk score category compared to the non-PTSD group. Multivariable generalized linear regression analysis identified PTSD as an independent predictor of presence and extent of atherosclerotic CAD (p <0.01). During a mean follow-up of 42 months, the death rate was higher in the PTSD compared to the non-PTSD group (15, 17.1%, vs 57, 10.4%, p = 0.003). Multivariable survival regression analyses revealed a significant linkage between PTSD and mortality and between CAC and mortality. After adjustment for risk factors, relative risk (RR) of death was 1.48 (95% confidence interval [CI] 1.03 to 2.91, p = 0.01) in subjects with PTSD and CAC score >0 compared to subjects without PTSD and CAC score equal to 0. With a CAC score equal to 0, risk of death was not different between subjects with and without PTSD (RR 1.04, 95% CI 0.67 to 6.82, p = 0.4). Risk of death in each CAC category was higher in subjects with PTSD compared to matched subjects without PTSD (RRs 1.23 for CAC scores 1 to 100, 1.51 for CAC scores 101 to 400, and 1.81 for CAC scores ≥400, p <0.05 for all comparisons). In conclusion, PTSD is associated with presence and severity of coronary atherosclerosis and predicts mortality independent of age, gender, and conventional risk factors.     

Influence of resting heart rate on mortality in patients undergoing coronary angiography (from the Ludwigshafen Risk and Cardiovascular Health [LURIC] study)

Atherosclerosis is the main cause of cardiovascular disease, but the extent of atherosclerosis in individual patients is difficult to estimate. A biomarker of the atherosclerotic burden would be very valuable. The aim of the present study was to evaluate the association of plasma osteoprotegerin (OPG) to clinical and subclinical atherosclerotic disease in a large community-based, cross-sectional population study. In the Copenhagen City Heart Study, OPG concentrations were measured in 5,863 men and women. A total of 494 participants had been hospitalized for ischemic heart disease or ischemic stroke, and compared to controls, this group with clinical atherosclerosis had higher mean OPG (1,773 vs 1,337 ng/L, p <0.001) and high-sensitivity C-reactive protein (2.3 vs 1.6 mg/L, p <0.001). In a multivariate model with age, gender, body mass index, hypertension, diabetes, hypercholesterolemia, smoking status, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and OPG, OPG remained significantly associated with clinical atherosclerosis (p <0.01); high-sensitivity C-reactive protein, in contrast, did not (p = 0.74). In the control group without clinical atherosclerosis, OPG was independently associated with hypertension, diabetes, hypercholesterolemia, smoking, and subclinical peripheral atherosclerosis as measured by ankle brachial index. For each doubling of the plasma OPG concentration, the risk for subclinical peripheral atherosclerosis increased by 50% (p <0.001) after multivariate adjustment. In conclusion, OPG appears to be a promising biomarker of atherosclerosis that is independently associated with traditional risk factors of atherosclerosis, subclinical peripheral atherosclerosis, and clinical atherosclerotic disease such as ischemic heart disease and ischemic stroke.     

Frequency of abdominal aortic aneurysm in patients >60 years of age with coronary artery disease

Using B-mode ultrasound, we studied the prevalence of abdominal aortic aneurysm (AAA; diameter > or =3 cm) and its predictive risk factors in 109 consecutive patients who were >60 years of age and had coronary artery disease (CAD). A group of 60 age-matched patients who did not have CAD served as controls. The prevalence of AAA was higher in the CAD group than in the control group (14%, 16 of 109, vs 3%, 2 of 60, p <0.05). By multivariate analysis, only smoking was strongly associated with AAA (odds ratio 4.86, 95% confidence interval 1.55 to 15.25). In contrast, presence of diabetes mellitus was negatively associated with AAA in univariate analysis (odds ratio 0.11, 95% confidence interval 0.01 to 0.83) and a strong trend of inverse association remained in multivariate analysis (odds ratio 0.12, 95% confidence interval 0.01 to 1.03). Thus, systematic screening can detect AAA in 1 of 7 patients who are >60 years of age and have CAD. AAA shares some, but not all, risk factors of atherosclerosis.     

The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects.

OBJECTIVES: This study sought to prospectively evaluate the relationship between plasma osteoprotegerin (OPG), inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], coronary artery calcification (CAC), and cardiovascular events in patients with type 2 diabetes. BACKGROUND: Arterial calcification is a prominent feature of atherosclerosis and is associated with an increased risk of cardiovascular events. Osteoprotegerin is a cytokine that has recently been implicated in the regulation of vascular calcification. METHODS: A total of 510 type 2 diabetic patients (53 +/- 8 years; 61% male) free of symptoms of cardiovascular disease were evaluated by CAC imaging. Risk factors, hs-CRP, IL-6, and OPG levels were measured. Patients were followed up for cardiovascular events (cardiac death, myocardial infarction, acute coronary syndrome, late revascularization, and nonhemorrhagic stroke). RESULTS: Significant CAC (>10 Agatston units) was seen in 236 patients (46.3%); OPG was significantly elevated in patients with increased CAC. In multivariable analyses, OPG retained a strong association with elevated CAC scores after adjustment for age, gender, and other risk factors (odds ratio = 2.84, 95% confidence interval 2.2 to 3.67; p < 0.01). Sixteen cardiovascular events occurred during a mean follow-up of 18 +/- 5 months. The waist-to-hip ratio, United Kingdom Prospective Diabetes Study (UKPDS) risk score, OPG level, and CAC score were significant predictors of time to cardiovascular events in a univariate Cox proportional hazards model. In the multivariate model, the CAC score was the only independent predictor of adverse events. Levels of hs-CRP and IL-6 were related to neither the extent of CAC nor short-term events. CONCLUSIONS: A high proportion of asymptomatic diabetic patients have significant subclinical atherosclerosis. Of the biomarkers studied, only OPG predicted both subclinical disease and near-term cardiovascular events. Therefore, measurement of OPG merits further investigation as a simple test for identifying high-risk type 2 diabetic patients.     

Relation between the incidence, location, and extent of thoracic aortic atherosclerosis detected by transesophageal echocardiography and the extent of coronary artery disease by angiography

Atherosclerotic lesions in the thoracic aorta detected by transesophageal echocardiography (TEE) have been correlated with coronary artery disease (CAD). We determined whether simple or complex aortic plaques seen on transesophageal echocardiogram correlated with extent, location, and severity of CAD. The study population consisted of 188 patients who underwent TEE and coronary angiography. Atherosclerotic plaques seen on transesophageal echocardiogram were defined as (1) complex plaques in the presence of protruding atheroma ≥4-mm thickness, mobile debris, or plaque ulceration or (2) simple plaques in the absence of findings consistent with complex plaques. Extent of CAD was grouped into 4 groups according to number of coronary vessels with ≥70% stenosis. Numbers of patients with CAD with 0-, 1-, 2-, and 3-vessel disease were 99, 31, 28, and 30 respectively. Compared to patients without CAD, patients with CAD (n = 89) had a significantly greater prevalence of aortic atherosclerotic plaques irrespective of degree of plaque complexity or location (p <0.05). Multivariate analysis found that hypertension (odds ratio 3.0, 95% confidence interval 1.3 to 7.0, p = 0.013), diabetes mellitus (odds ratio 2.4, 95% confidence interval 1.1 to 4.9, p = 0.022), and aortic plaque (odds ratio 3.8, 95% confidence interval 1.8 to 8.2, p = 0.001) were significantly associated with CAD. There was a significant relation between simple and complex aortic plaques with increasing severity of CAD (p <0.001). Multivariate logistic regression analysis showed that complex plaque in the descending aorta (odds ratio 5.4, 95% confidence interval 1.8 to 16.4, p = 0.003) was the strongest predictor of CAD. In conclusion, simple and complex thoracic atherosclerotic plaques detected by TEE are associated with increasing severity of CAD. Complex plaque in the descending aorta was the strongest association with presence of CAD.     

The association of differing measures of overweight and obesity with prevalent atherosclerosis: the Dallas Heart Study.

OBJECTIVES: This study sought to evaluate the associations between different measures of obesity and prevalent atherosclerosis in a large population-based cohort. BACKGROUND: Although obesity is associated with cardiovascular mortality, it is unclear whether this relationship is mediated by increased atherosclerotic burden. METHODS: Using data from the Dallas Heart Study, we assessed the association between gender-specific obesity measures (i.e., body mass index [BMI]; waist circumference [WC]; waist-to-hip ratio [WHR]) and prevalent atherosclerosis defined as coronary artery calcium (CAC) score >10 Agatston units measured by electron-beam computed tomography and detectable aortic plaque measured by magnetic resonance imaging. RESULTS: In univariable analyses (n = 2,744), CAC prevalence was significantly greater only in the fifth versus first quintile of BMI, whereas it increased stepwise across quintiles of WC and WHR (p trend <0.001 for each). After multivariable adjustment for standard risk factors, prevalent CAC was more frequent in the fifth versus first quintile of WHR (odds ratio 1.91, 95% confidence interval 1.30 to 2.80), whereas no independent positive association was observed for BMI or WC. Similar results were observed for aortic plaque in both univariable and multivariable-adjusted analyses. The c-statistic for discrimination of prevalent CAC was greater for WHR compared with BMI and WC in women and men (p < 0.001 vs. BMI; p < 0.01 vs. WC). CONCLUSIONS: We discovered that WHR was independently associated with prevalent atherosclerosis and provided better discrimination than either BMI or WC. The associations between obesity measurements and atherosclerosis mirror those observed between obesity and cardiovascular mortality, suggesting that obesity contributes to cardiovascular mortality via increased atherosclerotic burden.     

The prevalence of coronary artery calcium among diabetic individuals without known coronary artery disease

OBJECTIVES: We sought to examine the age and gender distribution of coronary artery calcium (CAC) by diabetes status in a large cohort of asymptomatic individuals. BACKGROUND: Among individuals with diabetes, coronary artery disease (CAD) is a major cause of morbidity and mortality. Electron-beam tomography (EBT) quantifies CAC, a marker for atherosclerosis. METHODS: Screening for CAC by EBT was performed in 30,904 asymptomatic individuals stratified by their self-reported diabetes status, gender, and age. The distribution of CAC across the strata and the association between diabetes and CAC were examined. RESULTS: Compared with nondiabetic individuals (n = 29,829), those with diabetes (n = 1,075) had higher median CAC scores across all but two age groups (women 40 to 44 years old and men and women > or =70 years old). Overall, the likelihood of having a CAC score in the highest age/gender quartile was 70% greater for diabetic individuals than for their nondiabetic counterparts. CONCLUSIONS: Younger diabetic individuals appear to have calcified plaque burden comparable to that of older individuals without diabetes. These findings call for future research to determine if EBT-CAC screening has an incremental value over the current CAD risk assessment of individuals with diabetes.     

Association among plasma levels of monocyte chemoattractant protein-1, traditional cardiovascular risk factors, and subclinical atherosclerosis

OBJECTIVES: We sought to evaluate the association between plasma levels of monocyte chemoattractant protein (MCP)-1 and the risk for subclinical atherosclerosis. BACKGROUND: Monocyte chemoattractant protein is a chemokine that recruits monocytes into the developing atheroma and may contribute to atherosclerotic disease development and progression. Plasma levels of MCP-1 are independently associated with prognosis in patients with acute coronary syndromes, but few population-based data are available from subjects in earlier stages of atherosclerosis. METHODS: In the Dallas Heart Study, a population-based probability sample of adults in Dallas County /=10) for subjects in the second, third, and fourth quartiles were 1.30 (95% confidence interval [CI] 0.99 to 1.73), 1.60 (95% CI 1.22 to 2.11), and 2.02 (95% CI 1.54 to 2.63), respectively. The association between MCP-1 and CAC remained significant when adjusted for traditional cardiovascular risk factors, but not when further adjusted for age. CONCLUSIONS: In a large population-based sample, plasma levels of MCP-1 were associated with traditional risk factors for atherosclerosis, supporting the hypothesis that MCP-1 may mediate some of the atherogenic effects of these risk factors. These findings support the potential role of MCP-1 as a biomarker target for drug development.     

Relation of a coronary artery calcium score higher than 400 to coronary stenoses detected using multidetector computed tomography and to traditional cardiovascular risk factors

Coronary artery calcium (CAC) is an excellent surrogate for atherosclerosis. However, this calcium is nonspecific for obstructive heart disease. This study sought to determine (1) the frequency of significant computed tomographic (CT) angiographic stenoses as a function of CAC scores, and (2) whether high CAC scores were associated with these stenoses independent of traditional risk factors. Subjects (n = 664) underwent Agatston CAC scoring and multidetector CT angiography using current 64-slice technology. Significant stenoses were defined as >60% diameter compromise. Self-reported risk factors and frequency of stenoses were analyzed as a function of CAC scores. The prevalence of risk factors increased significantly as CAC scores increased. Significant univariate associations included age (p <0.001), male gender (p <0.001), hypertension (p <0.001), and hyperlipidemia (p <0.001). There was also a significant association between CAC scores and the frequency of significant CT angiographic stenoses (p <0.001 for trend). The frequency of CT angiographic stenoses increased as CAC scores increased, with 7.9%, 8.3%, 14.5%, and 27.2% prevalences of significant stenoses in those with CAC scores of 1 to 100, 101 to 400, 401 to 1,000, and >1,000, respectively. Conversely, no significant lesions were found in those with no CAC. Multivariable logistic regression analysis controlling for traditional risk factors showed odds ratios for CAC score of 401 to 1,000 and >1,000 for having significant stenoses of 3.1 (95% confidence interval 1.6 to 6.0) and 6.9 (95% confidence interval 3.5 to 13.5), respectively. In conclusion, a CAC score >400 was significantly associated with multidetector CT angiographic stenoses independently of traditional risk factors.     

Parathyroid hormone and vitamin D levels are independently associated with calcific aortic stenosis.

BACKGROUND: In calcific aortic valve disease, the early lesion is similar to atherosclerotic plaque, but later calcification prevails. Parathyroid hormone (PTH) and vitamin D are the principal calcium pool regulators, so the present study was designed to assess their association with aortic stenosis (AS) in patients with significant coronary artery disease (CAD), and preserved renal function. METHODS AND RESULTS: The 122 consecutive patients with AS (mean gradient > or =30 mmHg) plus CAD, and 101 patients with nonobstructive aortic sclerosis (mean gradient < or =10 mmHg) plus CAD, as controls, were prospectively enrolled. The AS patients were older (71+/-7 vs 66+/-7 years; p<0.001), had higher serum intact (i)PTH (51.4 [39-70] vs 37.4 [27-50] pg/ml; p<0.001), and lower plasma vitamin D (32.0 [25-40] vs 35.8 [27-55] nmol/L; p=0.003) levels than those with aortic sclerosis. The groups did not differ significantly in creatinine level (93 [82-105] vs 96 [85-107] micromol/L, p=0.19), calcium - phosphate product, occurrence of hypertension, smoking, diabetes, dyslipidemia, or body mass index. The iPTH (odds ratio (OR) 1.04, 95% confidence interval (CI) 1.02-1.05; p<0.001) and vitamin D levels (OR 0.97, 95% CI 0.95-0.99; p=0.003) were independently associated with AS. CONCLUSION: Higher serum iPTH with lower vitamin D levels were independently associated with calcific AS in CAD patients.     

Atherosclerosis is associated with delirium after coronary artery bypass graft surgery

OBJECTIVES: To investigate whether atherosclerosis of the ascending aorta, internal carotid arteries, and coronary arteries is predictive of postoperative delirium in subjects undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Prospective cohort study. SETTING: Boston Veterans Affairs Healthcare System. PARTICIPANTS: Thirty-six male veterans undergoing primary CABG surgery. MEASUREMENTS: Subjects underwent Duplex ultrasound to assess stenosis in the internal carotid arteries. Information on the ascending aortic plaque, as assessed by transesophageal echocardiogram, and the number of coronary vessels bypassed was collected. To create an atherosclerosis score, the number of atherosclerotic areas was added. A validated delirium battery was administered to the subjects preoperatively and on postoperative Days 2 and 5. RESULTS: Fifteen subjects (41.7%) developed delirium postoperatively. In bivariate analysis, carotid stenosis of 50% or more (relative risk (RR)=3.5, 95% confidence interval (CI)=1.5-8.1) and moderate-severe ascending aortic plaque (RR=2.9, 95% CI=1.0-8.5) were significantly associated with the development of delirium. There was a trend toward a significant association for three or more vessels bypassed (RR=9.6, 95% CI=0.6-145.3). After controlling for age, baseline cognition, and medical comorbidity, the atherosclerosis score was significantly associated with postoperative delirium (adjusted RR=2.7, 95% CI=1.1-6.8). CONCLUSION: In this preliminary report, atherosclerosis in the carotid arteries, aorta, and coronary circulation is associated with the development of delirium after CABG surgery. Further investigation into atherosclerosis as a risk factor for delirium is warranted.     

Ethnic differences in coronary artery calcium in a healthy cohort aged 60 to 69 years

Measurement of coronary artery calcium (CAC) has been proposed as a screening tool, but CAC levels may differ according to race and gender. Racial/ethnic and gender distributions of CAC were examined in a randomly selected cohort of 60- to 69-year-old healthy subjects. Demographic, race/ethnicity (R/E), and clinical characteristics and assessment of CAC were collected. There were 723 white/European, 105 African-American, 73 Hispanic, and 67 East Asian subjects (597 men, 369 women) included in this analysis. Men had a significantly higher prevalence of any CAC (score>10) than women (76% vs 41%; p<0.0001). For men, the unadjusted odds of having any CAC was 2.2 (95% confidence interval [CI] 1.3 to 3.8) for whites compared with African-Americans. For women, CAC scores were not significantly different across ethnic groups. After adjustment for coronary risk factors, African-American and East Asian R/E remained associated with a lower prevalence of CAC in men (adjusted odds ratios [ORs] 0.33 and 0.47, respectively), as well as older age (OR 1.2, 95% CI 1.1 to 1.3), known hyperlipidemia (OR 1.7, 95% CI 1.1 to 2.7), and history of hypertension (OR 2.2, 95% CI 1.4 to 3.3). In women, Asian R/E (OR 2.5, 95% CI 1.1 to 5.7), history of smoking (adjusted OR 2.8, 95% CI 1.3 to 6.1), and known hyperlipidemia (adjusted OR 2.0, 95% CI 1.3 to 3.1) were associated with a higher prevalence of CAC independent of other risk factors. In conclusion, our data indicate that the presence of CAC varied significantly across selected race/ethnic groups independent of traditional cardiovascular risk factors.     

Osteoprotegerin, but not osteopontin, as a potential predictor of vascular calcification in normotensive subjects

We conducted a cross-sectional observation study that included 500 asymptomatic subjects to investigate the relationship between bone metabolism and coronary artery calcification (CAC) in hypertensive conditions. Osteoprotegerin (OPG) and osteopontin (OPN) levels and their associations with hypertension were analyzed to predict CAC in 316 subjects. Multislice computed tomography was used to quantify CAC. Multivariate analysis of variance was used to test the non-interactive effects of hypertension, CAC severity and biomarker levels, and the logistic regression model was applied to predict the risk of CAC. OPG and OPN concentrations were significantly higher in the hypertensive than the normotensive subjects, at 3.0 (2.3-4.0) pmol l(-1) and 51 (21-136) ng ml(-1) vs. 2.4 (2.0-3.0) pmol l(-1) and 41 (13-63) ng ml(-1), respectively. The OPG level, but not OPN level, increased with age (r = 0.29; P = 0.0001). Zero or minimal CAC (<10 Agatston units (AU)) was observed in 63% of the subjects, mild (11-100 AU) in 17%, moderate (101-400 AU) in 12% and severe (401-1000 AU)-to-extensive (>1000 AU) in 8%. In hypertensive subjects, only glomerular filtration rate (GFR) (β = -0.67) and gender (β = 0.52) were significant predictors for CAC (R = 0.68). In normotensive patients, GFR (β = -0.81), gender (β = 0.48) and log-transformed OPG levels (β = 0.15) were significant predictors for CAC. OPG levels were associated with an increased risk of CAC in normotensive subjects only (odds ratio: 3.37; 95% confidence interval (1.63-6.57); P = 0.0002). OPG predicted a premature state of vascular calcification in asymptomatic normotensive individuals, and renal function significantly contributed to this process in both hypertensive and normotensive subjects.     

A novel method for evaluating human carotid artery elasticity: possible detection of early stage atherosclerosis in subjects with type 2 diabetes

We recently developed a novel method for evaluating the elasticity of arterial walls, the phased tracking method. Herein, we evaluated atherosclerosis of the carotid artery with this method in 242 individuals with type 2 diabetes. In multiple regression analysis of subject status, age, systolic blood pressure and hyperlipidemia were found to be independently associated with carotid artery elasticity values. We also measured currently established values for atherosclerosis, carotid artery IMT and baPWV, in these subjects. Carotid artery elasticity correlated with max IMT (r=0.291, p<0.01), plaque score (PS) (r=0.220, p<0.01) and baPWV (r=0.345, p<0.01). Elasticity, max IMT and plaque score, all correlated with the number of risk factors for atherosclerosis, i.e. hypertension, hyperlipidemia and smoking, in addition to diabetes, consistent with the view that these values reflect atherosclerosis. Importantly, however, in subjects with IMT <1.1mm, who are classified as not having atherosclerosis as defined by IMT criteria, only carotid artery elasticity correlated with the number of risk factors (p<0.05). These results suggest that (1) the measured carotid artery elasticity values reflect atherosclerosis and (2) our novel method has potential for detecting atherosclerosis in its early stage.     

Plasminogen activator inhibitor-1 is associated with coronary artery calcium in Type 1 diabetes

BackgroundElevated levels of plasminogen activator inhibitor-1 (PAI-1), the major inhibitor of fibrinolysis, is associated with coronary artery disease (CAD). This association may not be independent of factors related to insulin resistance (IR). Patients with Type 1 diabetes mellitus have increased CAD and an increase in sub-clinical CAD which develops earlier in life. It is not known if PAI-1 is associated with sub-clinical CAD in Type 1 diabetes or if this association is independent of IR.Methods and ResultsType 1 diabetes patients (n=560) and participants without diabetes (n=693) were assessed for coronary artery calcium (CAC), a surrogate for subclinical CAD, by electron-beam computed tomography. PAI-1 was associated with CAC in both Type 1 diabetes (OR=1.32, 95% CI=1.12-1.58) and non-diabetes (OR=1.34, 95% CI=1.13–1.58), after controlling for traditional risk factors not associated with IR. In Type 1 diabetes, the relationship between PAI-1 and CAC was strongest for younger participants (P=.02 for PAI-1-by-age interaction) after controlling for factors related to IR. PAI-1 was positively associated with CAC for Type 1 diabetes participants younger than 45 years of age.ConclusionPAI-1 levels are independently related to CAC in younger Type 1 diabetes participants. PAI-1 levels were not independently related to CAC in non-diabetes participants.     

Indexes of kidney function and coronary artery and abdominal aortic calcium (from the Framingham Offspring Study)

It is uncertain whether moderate chronic kidney disease (CKD) or measures of kidney function are associated with subclinical atherosclerosis as represented by coronary artery calcium (CAC) or abdominal aortic calcium (AAC). We used logistic and linear regression analyses to relate CKD (glomerular filtration rate <60 ml/min/1.73 m(2)), cystatin C (cysC), and microalbuminuria (MA) with CAC and AAC obtained using multidetector computed tomography in Framingham Heart Study Offspring participants (mean age 59 years, 55.3% women). Increased CAC and AAC were defined as > or =90th percentile age- and gender-specific cutpoints based on a healthy referent sample. Major cardiovascular disease risk factors were accounted for in multivariable models. Of 1,179 participants, 1,174 had AAC measurements and 1,147 had CAC measurements, 6.3% had CKD, and 8.3% had MA. CKD was not associated with CAC (multivariable-adjusted odds ratio [OR] for CKD 1.18, 95% confidence interval 0.59 to 2.36, p = 0.63) or AAC (multivariable-adjusted OR for CKD 1.11, 95% confidence interval 0.61 to 2.04, p = 0.73). CysC was associated with CAC in age- and gender-adjusted but not in multivariable models (age- and gender-adjusted OR for log cysC per SD increment and CAC 1.19, 95% confidence interval 1.01 to 1.41, p = 0.04; multivariable-adjusted OR 1.14, 95% confidence interval 0.95 to 1.38, p = 0.15). MA was not associated with CAC (OR 0.81, 95% confidence interval 0.41 to 1.61, p = 0.54). Neither cysC nor MA was significantly associated with AAC in age- and gender- or multivariable-adjusted models. In conclusion, CKD, cysC, and MA are not associated with CAC or AAC when accounting for cardiovascular disease risk factors.     

Heart Disease Risk Factors in Midlife Predict Subclinical Coronary Atherosclerosis More than 25 Years Later in Survivors without Clinical Heart Disease: The Rancho Bernardo Study

OBJECTIVES: To determine which of the classic modifiable coronary heart disease (CHD) risk factors, measured in midlife, are associated with subclinical coronary atherosclerosis in older age.
DESIGN: Prospective study.
SETTING: Community based.
PARTICIPANTS: Participants were 400 community-dwelling middle-aged adults who had no history of CHD at baseline (1972–1974), when CHD risk factors were measured, and who were still free of known CHD in 2000 to 2002.
MEASUREMENTS: Coronary artery plaque burden was assessed according to coronary artery calcium (CAC) score using computed tomography in 2000 to 2002.
RESULTS: Ordinal logistic regression analysis was used to compare baseline risk factors with severity of CAC. Mean age was 42 at baseline and 69 at the time of CAC assessment; 46.5% were male. In analyses adjusted for age, sex, and all other risk factors, one standard deviation increase in body mass index (odds ratio (OR)=1.24, 95% confidence interval (CI)=1.02–1.51; P =.03), cholesterol (OR=1.28, 95% CI=1.03–1.58; P =.020, pulse pressure (OR=1.24, 95% CI=1.03–1.50; P =.03), and log triglycerides (OR=1.22, 95% CI=0.99–1.50; P =.06) each independently predicted the presence and severity of coronary artery atherosclerosis.
CONCLUSION: Modifiable risk factors measured more than 25 years earlier influence plaque burden in elderly survivors without clinical heart disease.     

Relation of aortic valve calcium detected by cardiac computed tomography to all-cause mortality

Aortic valve calcium (AVC) can be quantified on the same computed tomographic scan as coronary artery calcium (CAC). Although CAC is an established predictor of cardiovascular events, limited evidence is available for an independent predictive value for AVC. We studied a cohort of 8,401 asymptomatic subjects (mean age 53 ± 10 years, 69% men), who were free of known coronary heart disease and were undergoing electron beam computed tomography for assessment of subclinical atherosclerosis. The patients were followed for a median of 5 years (range 1 to 7) for the occurrence of mortality from any cause. Multivariate Cox regression models were developed to predict all-cause mortality according to the presence of AVC. A total of 517 patients (6%) had AVC on electron beam computed tomography. During follow-up, 124 patients died (1.5%), for an overall survival rate of 96.1% and 98.7% for those with and without AVC, respectively (hazard ratio 3.39, 95% confidence interval 2.09 to 5.49). After adjustment for age, gender, hypertension, dyslipidemia, diabetes mellitus, smoking, and a family history of premature coronary heart disease, AVC remained a significant predictor of mortality (hazard ratio 1.82, 95% confidence interval 1.11 to 2.98). Likelihood ratio chi-square statistics demonstrated that the addition of AVC contributed significantly to the prediction of mortality in a model adjusted for traditional risk factors (chi-square = 5.03, p = 0.03) as well as traditional risk factors plus the presence of CAC (chi-square = 3.58, p = 0.05). In conclusion, AVC was associated with increased all-cause mortality, independent of the traditional risk factors and the presence of CAC.