Objective

To examine the correlations between intra-hepatic and intra-thoracic (total, epicardial, and pericardial) fat deposition with cardiovascular disease (CVD) risk factors and subclinical atherosclerosis burden in healthy, recently postmenopausal women.

Methods

Women screened for the Kronos Early Estrogen Prevention Study (mean age 52.9 years) who underwent electron beam or multidetector computed tomography (CT) imaging for the quantification of intra-hepatic fat and thoracic adipose tissue, and coronary artery calcification (CAC) were included (n= 650).

Results

Higher levels of intra-hepatic and thoracic fat were each associated with CVD risk markers. After adjustment for BMI, the associations for intra-hepatic fat with hs-CRP and insulin persisted (r= 0.21 and 0.19, respectively; P<0.001), while those between thoracic fat indices and lipids persisted (r for total thoracic fat with HDL, LDL, and triglycerides= −0.16, 0.11, and 0.11, respectively, P<0.05). Total thoracic fat was associated with CAC after initial multivariable adjustment (odds ratio [OR] of 2nd, 3rd, and 4th vs. 1st quartile and [95% confidence intervals]: 0.8 [0.4–1.6], 1.5 [0.8–2.9], and 1.8 [1.0–3.4]; P for linear trend=0.017) and was only slightly attenuated after additional adjustment for BMI. Associations between total thoracic fat and CVD risk markers and CAC appeared due slightly more to associations with epicardial than pericardial fat.

Conclusion

While hepatic fat is related to hs-CRP and insulin, cardiac fat is associated with subclinical atherosclerosis as demonstrated by CAC. Cardiac fat may represent a useful marker for increased CVD risk beyond the standard adiposity measures of BMI and WC.

OBJECTIVE

It is unclear whether coronary artery calcium (CAC) is effective for risk stratifying patients with diabetes in whom treatment decisions are uncertain.

RESEARCH DESIGN AND METHODS

Of 44,052 asymptomatic individuals referred for CAC testing, we studied 2,384 individuals with diabetes. Subjects were followed for a mean of 5.6 ± 2.6 years for the end point of all-cause mortality.

RESULTS

There were 162 deaths (6.8%) in the population. CAC was a strong predictor of mortality across age-groups (age <50, 50–59, ≥60), sex, and risk factor burden (0 vs. ≥1 additional risk factor). In individuals without a clear indication for aspirin per current guidelines, CAC stratified risk, identifying patients above and below the 10% risk threshold of presumed aspirin benefit.

CONCLUSIONS

CAC can help risk stratify individuals with diabetes and may aid in selection of patients who may benefit from therapies such as low-dose aspirin for primary prevention.

Objective

To investigate whether leptin and adiponectin are associated with body fat composition in a South Asian population independent of metabolic variables.

Design

Cross-sectional study

Subjects

150 South Asian men and women, between the ages of 45–79 years, in the San Francisco Bay Area without pre-existing clinical cardiovascular disease.

Measurements

Blood samples were obtained to measure glucose metabolism variables, lipid profiles and adipokines. Total body fat was determined using dual-energy x-ray absorptiometry. Abdominal computed tomography was used to measure subcutaneous, visceral, and hepatic fat.

Results

Average body mass index (BMI) was overweight at 26.1±4.6 kg/m2 and did not differ by sex. However, women had significantly more total body fat (p<0.001) and subcutaneous fat (p<0.001) than men, while men had significantly more visceral fat (p<0.001) and hepatic fat (p=0.04) than women. Women had significantly higher levels of adiponectin (p<0.01) and leptin (p<0.01). In sex-stratified analyses, leptin was strongly associated with all body composition measures in women (p<0.05) as well as in men (p<0.05 except for hepatic fat) while there was an insignificant trend towards an inverse association between adiponectin and body composition in both women and men which was significant in combined bivariate analyses. In multivariate analyses, leptin was strongly associated with all measures of adiposity, including BMI (p<0.001), total body fat (p<0.001), visceral fat (p<0.001), and hepatic fat (p=0.01). However, adiponectin’s inverse association with adiposity was significantly attenuated by high-density lipoprotein (HDL), triglycerides, and insulin resistance. The association between adipokines and diabetes was markedly attenuated after adjusting for body composition.

Conclusion

Despite only modestly elevated BMI, South Asians have elevated levels of total and regional adiposity. Leptin is strongly associated with adiposity while adiponectin’s association with adiposity is attenuated by metabolic variables in South Asians. Adipokines in association with adiposity play an important role in the development of diabetes.

Background

Guidelines for the management of patients with suspected coronary artery disease (CAD) rely on the age, sex, and angina typicality-based pre-test probabilities of angiographically significant CAD derived from invasive coronary angiography (“Guideline Probabilities”). Reliability of Guideline Probabilities has not been investigated in patients referred to noninvasive CAD testing.

Methods and Results

We identified 14048 consecutive patients with suspected CAD who underwent coronary computed tomographic angiography (CTA) Angina typicality was recorded using accepted criteria. Pre-test likelihoods of CAD with ≥50% diameter stenosis (CAD50) and ≥70% diameter stenosis (CAD70) were calculated using Guideline Probabilities. CTA images were evaluated by ≥1 expert reader to determine presence of CAD50 and CAD70. Typical angina was associated with the highest prevalence of CAD50 (40% in men, 19% in women) and CAD70 (27% men, 11% women) when compared to other symptom categories (p<0.001 for all). Observed CAD50 and CAD70 prevalence were substantially lower than that predicted by Guideline Probabilities in the overall population (18% vs. 51% for CAD50, 10% vs. 42% for CAD70, p<0.001), driven by pronounced differences in patients with atypical angina (15% vs. 47% for CAD50, 7% vs. 37% for CAD70) and typical angina (29% vs. 86% for CAD50, 19% vs. 71% for CAD70). Marked overestimation of disease prevalence by Guideline Probabilities was found at all participating centers and across all sex and age subgroups.

Conclusion

In this multinational study of patients referred for coronary CTA, determination of pre-test likelihood of angiographically significant CAD by the invasive angiography-based Guideline Probabilities greatly overestimates the actual prevalence of disease.

Objectives

To test the diagnostic accuracy of myocardial CT perfusion (CTP) imaging using color and gray scale image analysis.

Background

Current myocardial CTP techniques have varying diagnostic accuracy and are prone to artifacts that impair detection. This study evaluated the diagnostic accuracy of color and/or gray-scale CTP and the application of artifact criteria to detect hypoperfusion.

Methods

Fifty-nine prospectively-enrolled patients with abnormal single photon emission computed tomography (SPECT) studies were analyzed. True hypoperfusion was defined if SPECT hypoperfusion corresponded to obstructive coronary stenoses on CT angiography (CTA). CTP applied color and gray scale myocardial perfusion maps to resting CTA images. Criteria for identifying artifacts were also applied during interpretation.

Results

Using combined SPECT plus CTA as the diagnostic standard, abnormal myocardial CTP was present in 33 (56%) patients, 19 suggesting infarction and 14 suggesting ischemia. Patient-level color and gray scale myocardial CTP sensitivity to detect infarction was 90%, with specificity 80%, and negative and positive predictive value of 94% and 68%. To detect ischemia or infarction, CTP specificity and positive predictive value were 92% while sensitivity was 70%. Gray scale myocardial CTP had slightly lower specificity but similar sensitivity. Myocardial CTP artifacts were present in 88% of studies and were identified using our criteria.

Conclusions

Color and gray scale myocardial CTP using resting CTA images identified myocardial infarction with high sensitivity as well as infarction or ischemia with high specificity and positive predictive value without additional testing or radiation. Color and gray scale CTP had slightly better specificity than gray scale alone.

OBJECTIVE

While metabolic syndrome (MetS) and diabetes confer greater cardiovascular disease (CVD) risk, recent evidence suggests that individuals with these conditions have a wide range of risk. We evaluated whether screening for coronary artery calcium (CAC) and carotid intimal-medial thickness (CIMT) can improve CVD risk stratification over traditional risk factors (RFs) in people with MetS and diabetes.

RESEARCH DESIGN AND METHODS

We assessed CAC and CIMT in 6,603 people aged 45–84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). Cox regression examined the association of CAC and CIMT with coronary heart disease (CHD) and CVD over 6.4 years in MetS and diabetes.

RESULTS

Of the subjects, 1,686 (25%) had MetS but no diabetes and 881 (13%) had diabetes. Annual CHD event rates were 1.0% among MetS and 1.5% for diabetes. Ethnicity and RF-adjusted hazard ratios for CHD for CAC 1–99 to ≥400 vs. 0 in subjects with neither MetS nor diabetes ranged from 2.6 to 9.5; in those with MetS, they ranged from 3.9 to 11.9; and in those with diabetes, they ranged from 2.9 to 6.2 (all P < 0.05 to P < 0.001). Findings were similar for CVD. CAC increased the C-statistic for events (P < 0.001) over RFs and CIMT in each group while CIMT added negligibly to prediction over RFs.

CONCLUSIONS

Individuals with MetS or diabetes have low risks for CHD when CAC or CIMT is not increased. Prediction of CHD and CVD events is improved by CAC more than by CIMT. Screening for CAC or CIMT can stratify risk in people with MetS and diabetes and support the latest recommendations regarding CAC screening in those with diabetes.

Background

Coronary artery calcification (CAC) is associated with increased mortality risk in the general population. Although individuals with chronic kidney disease (CKD) are at markedly increased mortality risk, the incidence, prevalence, and prognosis of CAC in CKD is not well-understood.

Study Design

Cross-sectional observational study.

Setting and Participants

Analysis of 1,908 participants who underwent coronary calcium scanning as part of the multi-ethnic CRIC (Chronic Renal Insufficiency Cohort) Study.

Predictor

Estimated glomerular filtration rate (eGFR) computed using the Modification of Diet in Renal Disease (MDRD) Study equation, stratified by race, sex and diabetic status. eGFR was treated as a continous variable and a categorical variable compared to the reference range of >60 ml/min/1.73 m2

Measurements

CAC detected using CT scans using either an Imatron C-300 electron beam computed tomography scanner or multi-detector CT scanner. CAC was computed using the Agatston score, as a categorical variable. Analyses were performed using ordinal logistic regression.

Results

We found a strong and graded relationship between lower eGFR and increasing CAC. In unadjusted models, ORs increased from 1.68 (95% CI, 1.23–2.31) for eGFR from 50–59 to 2.82 (95% CI, 2.06–3.85) for eGFR of <30. Multivariable adjustment only partially attenuated the results (OR, 1.53; 95% CI, 1.07–2.20) for eGFR<30.

Limitations

Use of eGFR rather than measured GFR.

Conclusions

We demonstrated a graded relationship between severity of CKD and CAC, independent of traditional risk factors. These findings supports recent guidelines that state that if vascular calcification is present, it should be considered as a complementary component to be included in the decision making required for individualizing treatment of CKD.

OBJECTIVE

We hypothesized that insulin resistance, measured by the homeostatic model assessment of insulin resistance (HOMA), is independently associated with prevalent and incident extra-coronary calcification (ECC).

METHODS

We studied calcium scores of the aortic valve (AVC), mitral valve (MVC), thoracic aorta (TAC) and aortic valve root (AVR) in 6,104 MESA participants not on diabetes medication who had baseline cardiac CT scans; 5,312 had follow-up scans (mean 2.4y). Relative-risk regression modeled prevalent and incident ECC adjusted for baseline demographics (model 1), and additionally for CVD risk factors (model 2).

RESULTS

In model 1, prevalence and incidence risk-ratios for the highest versus lowest quartile of HOMA were 20–30% higher in all ECC locations (p-value for trend ≤0.05 for all but incident-AVC). In model 2, all associations were attenuated, primarily by adjustment for metabolic syndrome components.

CONCLUSIONS

HOMA has a positive and graded association with ECC, but not independently of cardiovascular risk factors—particularly metabolic syndrome components.

Background

The JUPITER trial demonstrated that some patients with LDL-C <130 mg/dL and hsCRP ≥2 mg/L benefit from rosuvastatin, although absolute event rates were low. We sought to determine whether coronary artery calcium (CAC) may further risk stratify a JUPITER-eligible population, and to compare hsCRP vs. CAC for risk prediction in otherwise JUPITER-eligible participants.

Methods

A total of 950 MESA participants met all JUPITER entry criteria. We compared CHD and CVD event rates and multivariable-adjusted hazard ratios after stratifying by both presence and burden of CAC (0, 1–100, >100). We also calculated 5-year number needed to treat (NNT5) by applying the benefit observed in JUPITER to the observed event rates within each CAC strata.

Findings

Median follow-up was 5.8 years. Approximately 47% of the MESA JUPITER population had CAC=0, and CHD event rates in this group were <1 per 1000 person-years. Over 2/3 of all CHD events occurred in the 25% of participants with CAC >100 (20.2 per 1000 person-years). For CHD, the predicted NNT5 for CAC 0, 1–100, and >100 was 549, 94, and 24 respectively. For CVD, the NNT5 was 124, 54, and 19. Amongst otherwise JUPITER-eligible patients, presence of CAC was associated with 4.3-fold increased CHD (95% CI 2.0 – 9.3) and 2.6-fold increased CVD (95% CI 1.5–4.5), while hsCRP was not associated with either CHD or CVD after multivariable adjustment.

Interpretation

Within MESA, approximately half of JUPITER-eligible participants had CAC=0 and experienced an extremely low 6-year event rate. Nearly all events occurred in patients with CAC. CAC appears to further risk stratify JUPITER-eligible patients and may be used to target a subgroup of patients expected to derive the most, and the least, absolute benefit from statin treatment. Focusing treatment on the subset of individuals with measurable atherosclerosis may represent a more appropriate allocation of resources.

Funding

NIH-NHLBI.

Background

Extent of atherosclerosis measured by amount of coronary artery calcium (CAC) in computed tomography (CT) has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS). These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS) for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods

Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor.

Results

Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26) and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179). Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224). The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected.

Conclusions

The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.

Background:

Aged garlic extract (AGE) and coenzyme Q10 (CoQ10) have been shown to affect multiple cardiovascular risk factors. The current study evaluates the effect of AGE combined with CoQ10 on inflammatory markers and progression of coronary atherosclerosis compared with placebo.

Methods and Results:

In this placebo-controlled, double-blind, randomized trial, 65 intermediate risk firefighters (age 55 ± 6 years) were treated with a placebo capsule or a capsule containing AGE and CoQ10 (AGE+CoQ10, 1200 and 120 mg, respectively) daily for 1 year. All participants underwent coronary artery calcium (CAC) scanning and C-reactive protein (CRP) at baseline and at 12 months. At 1 year, mean CAC progression was significantly lower in AGE+CoQ10 (32 ± 6 vs. 58 ± 8, P = 0.01) than placebo. Similarly, CRP were significantly decreased in AGE+CoQ10 compared with placebo (-0.12 ± 0.24 vs. 0.91 ± 0.56 mg/L, P < 0.05). After adjustment for age, gender, conventional cardiac risk factors, and statin therapy, AGE+CoQ10 was associated with 3.99 fold (95% 1.3–12.2, P = 0.01) lack of CAC progression compared with the placebo.

Conclusion:

AGE+CoQ10 are associated with beneficial effects on inflammatory markers and reduced progression of coronary atherosclerosis.

Objective

High-sensitivity C-reactive protein (hsCRP) levels are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The JUPITER trial has encouraged using hsCRP ≥2 mg/L to guide statin therapy; however the association of hsCRP to atherosclerosis, independent of obesity, remains unknown.

Methods and Results

We studied 6,760 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were stratified into 4 groups: non-obese/low hsCRP, non-obese/high hsCRP, obese/low hsCRP, and obese/high hsCRP. Using multivariable logistic and robust linear regression, we described the association with subclinical atherosclerosis, using coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). Mean BMI was 28.3 ± 5.5 kg/m2, and median hsCRP was 1.9 mg/L (0.84 – 4.26). High hsCRP, in the absence of obesity, was not associated with CAC and was mildly associated with cIMT. Obesity was strongly associated with CAC and cIMT independent of hsCRP. When obesity and high hsCRP were both present, there was no evidence of multiplicative interaction. Similar associations were seen among 2,083 JUPITER-eligible individuals.

Conclusions

High hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with cIMT in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independent of hsCRP status.

OBJECTIVE

We sought to determine whether insulin resistance predicts the incidence and progression of coronary artery calcification (CAC).

RESEARCH DESIGN AND METHODS

We studied 5,464 participants not on hypoglycemic therapy from the Multi-Ethnic Study of Atherosclerosis (MESA). Each had baseline homeostasis model assessment of insulin resistance (HOMA-IR) and baseline and follow-up CAC scores. Incident CAC was defined as newly detectable CAC; progression was defined as advancing CAC volume score at follow-up.

RESULTS

Median HOMA-IR was 1.2 (0.8–2.0). Across all ethnicities, there was a graded increase in CAC incidence and progression with increasing HOMA-IR. When compared with those in the 1st quartile, participants in the 2nd–4th quartiles had 1.2, 1.5, and 1.8 times greater risk of developing CAC. Median annualized CAC score progression was 8, 14, and 17 higher, respectively. However, HOMA-IR was not predictive after adjustment for metabolic syndrome components.

CONCLUSIONS

HOMA-IR predicts CAC incidence and progression, but not independently of metabolic syndrome.

OBJECTIVE

Coronary artery calcification (CAC) and thoracic aortic calcificatio (TAC) are frequently detected on ungated multi-detector computed tomography (MDCT) performed for lung evaluations. We sought to evaluate concordance of CAC and TAC scores on ungated (thoracic) and ECG-gated (cardiac) MDCT scans.

METHODS

Fifty patients, enrolled in the Genetic Epidemiology of COPD study (COPDGene), were recruited to undergo gated CAC scans using 64-detector row CT, in addition to the ungated thoracic studies already being obtained as part of their study evaluation. Coronary and thoracic calcium was measured similarly (Agatston score, requiring 3 contiguous voxels of >130 Hounsfield units) using low-dose ungated studies and ECG-gated MDCT performed at the same scanning session. Intertechnique scoring variability and concordance were calculated.

RESULTS

Correlations between gated and ungated CAC and TAC were excellent (r = 0.96). The relative differences (median variability) measured by ECG-gated vs. ungated MDCT were relatively high for CAC (44%) but not for TAC (8%). Prevalence of depicted CAC (n=33, 66%) and TAC (n=21, 42%) were coincident between ECG-gated and ungated MDCT, respectively (inter-technique concordance 100%). Bland-Altman plots for CAC demonstrated mean differences of 354 (CI 169–538) and 16.1(CI −89–121).

CONCLUSION

Low-dose ungated MDCT is reliable for prediction of the presence of CAC and assessment of Agatston score. Concordance between methods and between TAC and CAC is high. This technique should allow for atherosclerotic disease risk stratification among patients undergoing ungated lung CT evaluation without requiring additional scanning. Measurement of TAC is almost as accurate from gated CT, and CAC scores are highly concordant.

Objective

To establish the normal criterion of ascending aortic diameter (AAOD) measured by 64 Multi-Detector Computed Tomography (MDCT) and Electron Beam Computed Tomography (EBT) based on gender and age.

Methods

1442 consecutive subjects who were referred for evaluation of possible coronary artery disease underwent coronary CT angiography (CTA) and coronary artery calcium scanning (CACS) (55+11 years, 65% male) without known coronary heart disease, hypertension, chronic pulmonary and renal disease, diabetes and severe aortic calcification. The ascending aortic diameter, descending aortic diameter (DAOD), pulmonary artery (PAD) and chest anterioposterior diameter (CAPD), posterior border of sternal bone to anterior border of spine, were measured at the slice level of mid right pulmonary artery by using end systolic trigger image. The volume of four chambers, ejection fraction of left ventricle, and cardiac output were measured in 56% of the patients. Patients demographic information, age, gender, weight, height and body surface area (BSA), were recorded. The mean value and age specific and gender adjusted upper normal limits (mean + 2 standard deviations) were calculated. The linear correlation analysis was done between AAOD and all parameters. The reproducibility, wall thickness and difference between end systole and diastole were calculated.

Result

AAOD has significant linear association with age, gender, descending aortic diameter and pulmonary artery diameter (P<0.05). There is no significant correlation between AAOD and body surface area, four chamber volume, LVEF, CO and CAPD. The mean Intra-luminal AAOD was 31.1 ± 3.9mm and 33.6 ± 4.1 mm in females and males respectively. The upper normal limits (mean + 2 standard deviations) of Intra-luminal AAOD, mean+ standard deviation, was 35.6, 38.3 and 40 mm for females and 37.8, 40.5 and 42.6 mm for males in age group 20 to 40, 41 to 60, above 60 year respectively. Intra-luminal should parallel echocardiography and invasive angiography. Traditional cross sectional imaging (with computed tomography and magnetic resonance imaging) includes the vessel wall. The mean total AAOD was 33.5mm and 36.0 mm in females and males respectively. The upper normal limits (mean + 2 standard deviations) of Intra-luminal AAOD, mean+ standard deviation, was 38.0, 40.7 and 42.4 mm for females and 40.2, 42.9 and 45.0 mm for males in age group 20 to 40, 41 to 60, above 60 year respectively. The inter and intra observer, scanner and repeated measurement variability was low (R value >0.91, P<0.001, coefficient variation <3.2%). AAOD was 1.7 mm less in end-diastole than end systole(P<0.001).

Conclusion

The ascending aortic diameter increases with age and male gender. Gender specific and age adjusted normals for aortic diameters are necessary to differentiate pathologic atherosclerotic changes in the ascending aorta. Use of intra-luminal or total aortic diameter values depends on the comparison study that may be employed.

Background

Coronary artery calcium (CAC), carotid intima-media thickness, and left ventricular (LV) mass and geometry offer the potential to characterize incident cardiovascular disease (CVD) risk in clinically asymptomatic individuals. The objective of the study was to compare these cardiovascular imaging measures for their overall and sex-specific ability to predict CVD.

Methods and Results

The study sample consisted of 4965 Multi-Ethnic Study of Atherosclerosis participants (48% men; mean age, 62±10 years). They were free of CVD at baseline and were followed for a median of 5.8 years. There were 297 CVD events, including 187 coronary heart disease (CHD) events, 65 strokes, and 91 heart failure (HF) events. CAC was most strongly associated with CHD (hazard ratio [HR], 2.3 per 1 SD; 95% CI, 1.9 to 2.8) and all CVD events (HR, 1.7; 95% CI, 1.5 to 1.9). Most strongly associated with stroke were LV mass (HR, 1.3; 95% CI, 1.1 to 1.7) and LV mass/volume ratio (HR, 1.3; 95% CI, 1.1 to 1.6). LV mass showed the strongest association with HF (HR, 1.8; 95% CI, 1.6 to 2.1). There were no significant interactions for imaging measures with sex and ethnicity for any CVD outcome. Compared with traditional risk factors alone, overall risk prediction (C statistic) for future CHD, HF, and all CVD was significantly improved by adding CAC, LV mass, and CAC, respectively (all P<0.05).

Conclusions

There was no evidence that imaging measures differed in association with incident CVD by sex. CAC was most strongly associated with CHD and CVD; LV mass and LV concentric remodeling best predicted stroke; and LV mass best predicted HF.

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular events. We evaluated whether multidetector computed tomographic angiography (MDCTA) revealed a link between pre-dialysis CKD and coronary artery atherosclerosis.

We retrospectively analyzed 549 patients who underwent MDCTA. Patients were divided into 3 groups: normal glomerular filtration rate (GFR) (GFR >90 mL/min/1.73 m2 body surface area), mild CKD (>60GFR≤90 mL/min/1.73 m2), and moderate CKD (>30GFR≤60 mL/min/1.73 m2). Normality testing was performed to determine if continuous variables were modeled in Gaussian distribution before analysis of variance was applied. The χ2 test was used to compare GFR subgroups. Multiple linear regression was used to detect associations of total plaque score (TPS), segment involvement score (SIS), and segment stenosis score (SSS) with GFR. A model adjusted for covariates was applied.

Patients with mild CKD had a mean TPS 2.3 points higher than those with a normal GFR (P=0.002); patients with moderate CKD had a mean TPS 5.9 points higher than the referent (P <0.001). Patients with mild CKD had a mean SIS 1.1 points higher than those with a normal GFR (P=0.002); patients with moderate CKD had a mean SIS 2.4 points higher than the referent (P <0.001). Patients with mild CKD had a mean SSS 1.4 points higher than those with a normal GFR (P=0.004); patients with moderate CKD had a mean SSS 4.2 points higher than the referent (P <0.001). The use of MDCTA showed that mild and moderate pre-dialysis CKD are independent risk factors for coronary artery atherosclerosis.

Background

It is increasingly evident that patients with chronic kidney disease (CKD) are more likely to die from heart disease than kidney failure. This study evaluated whether pre- dialysis CKD is an independent risk factor for coronary artery calcium (CAC).

Methods

A total of 544 consecutive patients who underwent CAC scoring were analyzed. Eleven patients requiring hemodialysis were excluded. Patients were divided into three groups: normal glomerular filtration rate (GFR) (GFR > 90 mL/min/1.73 m2), mild CKD (90 ≥ GFR > 60 mL/min/1.73 m2), and moderate CKD (60 ≥ GFR > 30 mL/min/1.73 m2). Continuous and categorical variables were compared using analysis of variance and the χ2 statistic. A multiple logistic regression model was used for detecting the association between total CAC score and GFR. An unadjusted model was used, followed by a second model adjusted for covariates known to be related to CAC. Another multivariable binary logistic model predicting the presence of CAC (>10) was performed and odds of incidence of CAC (>10) were calculated among the three GFR subgroups.

Results

After adjustment for covariates, patients with mild CKD had mean CAC scores 175 points higher than those with the referent normal GFR (P = 0.048), while those with moderate CKD had mean CAC scores 693 points higher than the referent (P < 0.001). After adjustment for covariates, patients with mild CKD were found to be 2.2 times more likely (95% confidence interval 1.3–3.7, P = 0.004) and patients with moderate CKD were 6.4 times more likely (95% confidence interval 2.9–14.3, P < 0.001) to have incident CAC compared with the group with normal GFR.

Conclusion

Mild and moderate pre-dialysis CKD are independent risk factors for increased mean and incident CAC.

Background

Mitral annular calcification (MAC) is a fibrous, degenerative calcification of the mitral valve. The relationship between MAC and cardiovascular disease (CVD) risk factors is not well defined. Thus, we performed a cross-sectional study to determine which CVD risk factors are independently associated with MAC in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods

MESA includes 6,814 women and men ages 45–84 years old without apparent CVD in 4 ethnic groups (12% Chinese, 38% Caucasian, 22% Hispanic, and 28% African-American). MAC was defined by presence of calcium in the mitral annulus by cardiac computed tomography at enrollment. Multivariable logistic regression was used to evaluate relationships between MAC and CVD risk factors.

Results

The overall prevalence of MAC was 9%. The prevalence of MAC was highest in Caucasians (12%), followed by Hispanics (10%), African Americans (7%) and was lowest in Chinese (5%). Characteristics associated with MAC included age (p<0.01), female gender (p<0.01), increased body mass index (BMI) (p=0.03), and former smoking status (p<0.008). The MAC group had a higher prevalence of hypertension, diabetes mellitus (DM), and family history of heart attack (all p<0.001). After adjusting for all variables, age, female gender, diabetes mellitus, and increased BMI remained strongly associated with MAC.

Conclusions

Age, female gender, DM, and increased BMI were significantly associated with MAC. Prevalence of MAC was strongly associated with female gender and increasing age in all ethnicities.

While there is no doubt that high risk patients (those with >20% ten year risk of future cardiovascular event) need more aggressive preventive therapy, a majority of cardiovascular events occur in individuals at intermediate risk (10%–20% ten year risk). Accurate risk assessment may be helpful in decreasing cardiovascular events through more appropriate targeting of preventive measures. It has been suggested that traditional risk assessment may be refined with the selective use of coronary artery calcium (CAC) or other methods of subclinical atherosclerosis measurement. Coronary calcification is a marker of atherosclerosis that can be quantified with the use of cardiac CT and it is proportional to the extent and severity of atherosclerotic disease. The published studies demonstrate a high sensitivity of CAC for the presence of coronary artery disease but a lower specificity for obstructive CAD depending on the magnitude of the CAC. Several large clinical trials found clear, incremental predictive value of CAC over the Framingham risk score when used in asymptomatic patients. Based on multiple observational studies, patients with increased plaque burdens (increased CAC) are approximately ten times more likely to suffer a cardiac event over the next 3–5 years. Coronary calcium scores have outperformed conventional risk factors, highly sensitive C-reactive protein (CRP) and carotid intima media thickness (IMT) as a predictor of cardiovascular events. The relevant prognostic information obtained may be useful to initiate or intensify appropriate treatment strategies to slow the progression of atherosclerotic vascular disease. Current data suggests intermediate risk patients may benefit most from further risk stratification with cardiac CT, as CAC testing is effective at identifying increased risk and in motivating effective behavioral changes. This article reviews information pertaining to the clinical use of CAC for assessing coronary atherosclerosis as a useful predictor of coronary artery disease (CAD) in certain population of patients.

Objectives

To determine whether nitrogen-containing bisphosphonate (NCBP) therapy is associated with the prevalence of cardiovascular calcification.

Background

Cardiovascular calcification correlates with atherosclerotic disease burden. Experimental data suggest that NCBP may limit cardiovascular calcification, which has implications for disease prevention.

Methods

The relationship of NCBP use to the prevalence of aortic valve, aortic valve ring, mitral annulus, thoracic aorta, and coronary artery calcification (AVC, AVRC, MAC, TAC, and CAC, respectively) detected by computed tomography was assessed in 3,636 women within the Multi-Ethnic Study of Atherosclerosis (MESA) using regression modeling.

Results

Analyses were age-stratified because of a significant interaction between age and NCBP use (interaction p-values: AVC p<0.0001; AVRC p<0.0001; MAC p=0.002; TAC p<0.0001; CAC p=0.046). After adjusting for age, body mass index, demographics, diabetes, smoking, blood pressure, cholesterol levels, and statin, hormone replacement, and renin-angiotensin inhibitor therapy, NCBP use was associated with a lower prevalence of cardiovascular calcification in women ≥65 years old (prevalence ratio [95% confidence interval]: AVC 0.68 [0.41, 1.13]; AVRC 0.65 [0.51, 0.84]; MAC 0.54 [0.33, 0.93]; TAC 0.69 [0.54, 0.88]; CAC 0.89 [0.78, 1.02]), whereas calcification was more prevalent in NCBP users among the 2,181 women <65 years old (AVC 4.00 [2.33, 6.89]; AVRC 1.92 [1.42, 2.61]; MAC 2.35 [1.12, 4.84]; TAC 2.17 [1.49, 3.15]; CAC 1.23 [0.97, 1.57]).

Conclusions

Among women in the diverse MESA cohort, NCBPs were associated with decreased prevalence of cardiovascular calcification in older subjects, but more prevalent cardiovascular calcification in younger ones. Further study is warranted to clarify these age-dependent NCBP effects.

Background

Low serum parathyroid hormone (PTH) has been implicated as a primary biochemical marker of adynamic bone disease in individuals with chronic kidney disease (CKD) who undergo maintenance hemodialysis (MHD) treatment. We hypothesized that the malnutrition-inflammation complex is associated with low PTH levels in these patients and confounds the PTH-survival association.

Methods

We examined 748 stable MHD outpatients in Southern California and followed them for up to 5 years (10/2001-12/2006).

Results

In 748 MHD patients, serum PTH <150 pg/ml was more prevalent among non-Blacks and diabetics. There was no association between serum PTH and coronary artery calcification score, bone mineral density or dietary protein or calorie intake. Low serum PTH was associated with markers of protein-energy wasting and inflammation, and this association confounded the relationship between serum PTH and alkaline phosphatase. Although 5-year crude mortality rates were similar across PTH increments, after adjustment for the case-mix and surrogates of malnutrition and inflammation, a moderately low serum PTH in 100 to 150 pg/ml range was associated with the greatest survival compared to other serum PTH levels, i.e., a death hazard ratio of 0.52 (95% confidence interval: 0.29-0.92, p<0.001) compared to PTH of 300 to 600 pg/ml (reference).

Conclusions

Low serum PTH may be another facet of the malnutrition-inflammation complex in CKD, and after controlling for this confounder, a moderately low PTH in 100 to 150 pg/ml range appears associated with the greatest survival. Limitations of observational studies should be considered.

Largely on the basis of the first publication of findings of net harm with menopausal hormone treatment in the Women’s Health Initiative (WHI) hormone trials, current Food and Drug Administration recommendations limit menopausal hormone treatment to the “… shortest duration consistent with treatment goals …,” with goals generally taken to mean relief of menopausal symptoms and maximal duration as approximately 5 years. The WHI finding of net harm was due largely to the absence of beneficial effects on coronary heart disease incidence rates. Published analyses of WHI data by age or time since menopause find that excess coronary heart disease risk with menopausal hormone treatment is confined to more remotely menopausal or older women, with younger women showing nonsignificant trends toward benefit (the “timing hypothesis”). Moreover, a recently published reexamination of data from the WHI Estrogen plus Progestin trial suggests that reduced coronary heart disease risk may appear only after 5 to 6 years of treatment. Consistent with this finding, risk ratios for coronary heart disease were calculated as 1.08 (95% confidence interval, 0.86–1.36) in years 1 to 6 and as 0.46 (confidence interval, 0.28–0.78) in years 7 to 8+ in the WHI Estrogen Alone trial. Previous studies also support the beneficial effects of menopausal hormone treatment after prolonged exposure. Thus, current analyses do not support a generalized recommendation for short duration of menopausal hormone treatment. Rather, they suggest that current Food and Drug Administration practice guidelines should be reconsidered to allow individualized care based on risk:benefit considerations. New research is urgently needed evaluating influences of timing, duration, dose, route of administration, and agents on menopausal hormone treatment-related risks and benefits to better understand how to optimize recommendations for individual patients.

Many traditional and nontraditional risk factors contribute to vascular calcification among maintenance hemodialysis (MHD) patients. It is not clear whether coronary artery calcification (CAC) delineates a higher mortality risk independent of known risk factors. We examined 6-year (10/2001–9/2007) survival of 166 MHD patients, aged 53 ± 13 years, with baseline CAC scores. Patients were grouped into four CAC groups: 0, 1–100, 101–400, and 400+. The 101–400 and 400+ groups were associated with a significantly higher adjusted risk of death than CAC 0 with hazard ratios (HR) 8.5 (95% CI: 1.1–48.1, p = 0.02) and 13.3 (95% CI: 1.3–65.1, p = 0.01), respectively, independent of demographics, comorbidity, lipids and other cardiovascular risks, surrogates of bone disease, nutritional and inflammatory markers and dialysis dose. Total CAC [HR 6.7 (1.1–21.5, p = 0.03)] followed by the presence of CAC in the left main [4.6 (2.2–9.8, p = 0.001)] and left anterior descending artery [4.3 (2.1–14.2, p = 0.001)] were strong independent predictors of mortality even after adjusting for above covariates. Total and vessel-specific CAC predict mortality in MHD patients independent of traditional and nontraditional risk factors.