Incident coronary artery calcium among postmenopausal women

Recent studies have shown that individuals with 0 coronary artery calcium (CAC) scores have very low risk of coronary heart disease. In the Healthy Women Study, we evaluated development of new CAC among postmenopausal women (n = 272) over a 6-year period, age 62 at the 1st and 68 at the 3rd electron beam tomography (EBT) examination. At the 1st EBT, 155 of 272 (57%) women had 0 CAC. By the 3rd, 56 (36%) of these women had developed new CAC, including 38 with ≥5 Agatston units. There was practically no regression from having CAC at the 1st EBT to no CAC at the 3rd EBT. The risk of developing new CAC over 6 years among women with 0 CAC on their 1st EBT was strongly and significantly related to presence of both aortic calcium and carotid plaque at the time of 1st EBT. Baseline premenopausal risk factors, age 47, apolipoprotein B, body mass index (BMI) and triglycerides, were significant predictors of incident CAC as were the changes in BMI and low density lipoprotein cholesterol between premenopause and the 1st post exam, age 53. Risk factors measured premenopause and change in risk factors from premenopause to the 1st post exam and the extent of subclinical disease in other vascular beds are primary determinants of the risk of developing incident CAC in women over a 6-year period.     

Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease?

OBJECTIVES: We sought to determine clinical and laboratory correlates of calcification of the coronary arteries (CAs), aorta and mitral and aortic valves in adult subjects with end-stage renal disease (ESRD) receiving hemodialysis. BACKGROUND: Vascular calcification is known to be a risk factor for ischemic heart disease in non-uremic individuals. Patients with ESRD experience accelerated vascular calcification, due at least in part to dysregulation of mineral metabolism. Clinical correlates of the extent of calcification in ESRD have not been identified. Moreover, the clinical relevance of calcification as measured by electron-beam tomography (EBT) has not been determined in the ESRD population. METHODS: We conducted a cross-sectional analysis of 205 maintenance hemodialysis patients who received baseline EBT for evaluation of vascular and valvular calcification. We compared subjects with and without clinical evidence of atherosclerotic vascular disease and determined correlates of the extent of vascular and valvular calcification using multivariable linear regression and proportional odds logistic regression analyses. RESULTS: The median coronary artery calcium score was 595 (interquartile range, 76 to 1,600), values consistent with a high risk of obstructive coronary artery disease in the general population. The CA calcium scores were directly related to the prevalence of myocardial infarction (p < 0.0001) and angina (p < 0.0001), and the aortic calcium scores were directly related to the prevalence of claudication (p = 0.001) and aortic aneurysm (p = 0.02). The extent of coronary calcification was more pronounced with older age, male gender, white race, diabetes, longer dialysis vintage and higher serum concentrations of calcium and phosphorus. Total cholesterol (and high-density lipoprotein and low-density lipoprotein subfractions), triglycerides, hemoglobin and albumin were not significantly related to the extent of CA calcification. Only dialysis vintage was significantly associated with the prevalence of valvular calcification. CONCLUSIONS: Coronary artery calcification is common, severe and significantly associated with ischemic cardiovascular disease in adult ESRD patients. The dysregulation of mineral metabolism in ESRD may influence vascular calcification risk.     

Rates of progression of coronary calcium by electron beam tomography

In this study, we sought to determine the rate of progression of atherosclerosis using coronary calcium scores derived from electron beam tomography (EBT). We studied a variety of disease states (hypertension, high cholesterol, tobacco use, diabetes mellitus) followed for 1 to 6.5 years. We evaluated 299 asymptomatic persons (227 men and 72 women) who underwent 2 consecutive EBT scans at least 12 months apart. The average change in the calcium score (Agatston method) for the entire group was 33.2 +/- 9.2%/year. The treated group (receiving statins) demonstrated an average increase in calcium scores of 15 +/- 8%/year compared with 39 +/- 12%/year for untreated patients (p <0.001). Among the 60 patients on statin monotherapy, 37% had a decrease in the calcium score from baseline to follow-up scan. The relative increase in calcium scores did not vary significantly by gender or risk factors, with the exception of statin-treated hypercholesterolemic subjects. Scores of zero on the initial scan portend a low likelihood of significant calcific deposits on repeat scanning. Only 2 of 81 participants (2%) with scores of zero at baseline had scores >10 on repeat study. In this study, statin therapy induced a 61% reduction in the rate of coronary calcium progression. This study demonstrates that EBT may be a useful tool in assessing efficacy of different interventions to retard progression of atherosclerosis, noninvasively, over relatively short time periods.     

Electron beam tomography and angiography: sex differences

Background We sought to study a large cohort of symptomatic women to determine the clinical use of electron beam tomography (EBT), with evaluation of the sensitivity and specificity of obstructive coronary disease and the differences between premenopausal and postmenopausal cohorts. Methods Patients who underwent angiography for evaluation of coronary artery disease (CAD) and EBT within 3 months were enrolled. Receiver operating characteristic curves were used to establish relationships between EBT calcium scores and angiographic disease. Results We studied 1120 symptomatic patients, 387 women and 733 men. We found no significant differences with respect to sensitivity for obstructive disease (96% in men and women). However, women had a significantly higher specificity (46% in men versus 57% in women; P = .01). The area under the curves for coronary calcium score predicting angiographic disease was 0.85 for all patients and 0.84 in women. Evaluation of scores on the basis of age revealed a 14.4-year lag between men and women. One hundred thirty-five women had negative EBT study results (score, zero; no calcium present), with 6 with single-vessel disease and 129 with normal coronaries or nonobstructive disease only (negative predictive value, 96%). Conclusion EBT may have a great value in evaluation of women with possible CAD. The high sensitivity and high negative predictive value may serve as the basis for a new diagnostic approach to filter symptomatic women with suspected CAD before coronary angiography. (Am Heart J 2002;143:877-82.)     

Estrogen status correlates with the calcium content of coronary atherosclerotic plaques in women

BACKGROUND: Coronary artery calcium, a radiographic marker for atherosclerosis and a predictor of coronary heart disease (CHD), is less extensive in women than in men of the same age. The role of estrogen in the pathogenesis of coronary artery calcification is unknown. We examined the association of estrogen status with extent of calcification and atherosclerotic plaque in coronary arteries of deceased women. METHODS: Coronary arteries were obtained at autopsy from 56 white women age 18--98 yr, 46 postmenopausal and 10 premenopausal. Exclusion criteria included patients with coronary stents, coronary artery bypass surgery, and medical-legal cases. Medical records were reviewed for demographics, CHD risk factors, menstrual status, and use of estrogen replacement therapy. Contact microradiography of coronary arteries assessed true calcium content and atherosclerotic plaque area was analyzed histologically. RESULTS: The coronary arteries from estrogen-treated postmenopausal women had lower mean coronary calcium content (P = 0.002), mean plaque area (P < 0.0001), and calcium-to-plaque area ratio (P = 0.004) than those from untreated menopausal women. Estrogen status, age, diabetes, and hypertension predicted calcium and plaque area by univariate analysis. After controlling for these CHD risk factors, estrogen status remained an independent predictor of both calcium (P = 0.014) and plaque area (P = 0.001) in all women. Mean calcium area (P < 0.05) but not plaque area (P = 0.44) was significantly greater in women treated with estrogen replacement therapy than in premenopausal women. Coronary calcium (P < 0.007) and plaque area (P < 0.03) varied significantly with age in untreated postmenopausal women, but not in the estrogen-treated or premenopausal women (P = 0.33). CONCLUSIONS: Estrogen status is associated with coronary calcium and plaque area independent of age and CHD risk factors. Estrogen may modulate the calcium content of atherosclerotic plaques, as well as plaque area and may slow the progression of atherosclerosis in women.     

Coronary and aortic calcification among women 8 years after menopause and their premenopausal risk factors : the healthy women study.

In the Healthy Women Study, the relationship between cardiovascular risk factors measured premenopausally at age 48, use of hormone therapy, and coronary and aortic calcification at age 58 were evaluated among 169 women. Approximately 63% of women had no coronary calcification, but only 29% had no aortic calcification. Coronary calcification and aortic calcification were positively correlated with each other. There was a very strong association between low density lipoprotein cholesterol (LDL-C) level and coronary calcification. Among women with premenopausal levels of LDL-C <100 mg/dL, only 9% had a coronary calcium score >/=101 compared with 30% of women with an LDL-C >160 mg/dL. Only 5% of women with a high density lipoprotein cholesterol (HDL-C) level >60 mg/dL had high coronary scores. The level of HDL(2)-C was especially strongly inversely related to coronary calcium scores. Cigarette smoking was a very important determinant of both high aortic and high coronary calcium scores. Other risk factors associated with greater coronary calcium were higher systolic blood pressure, triglycerides levels, and blood glucose. Use of hormone replacement therapy was associated with less coronary calcium (NS). For both hormone replacement therapy users and nonusers, the levels of LDL-C and HDL-C measured premenopausally were predictors of coronary and aortic calcium scores. Thus, risk factors evaluated premenopausally are powerful predictors of coronary and aortic calcification, a marker of atherosclerosis, measured 8 years after menopause, 11 years later in these women.     

Prevalence and predictors of cardiovascular calcium in chronic kidney disease (from the Prospective Longitudinal RRI-CKD Study)

Although the determinants of cardiovascular calcium have been well described in dialysis patients, the prevalence and predictors in predialysis chronic kidney disease (CKD) are less known. One hundred six patients with CKD from the Renal Research Institute-CKD Study underwent multidetector computed tomography for the assessment of calcium deposition at the level of coronary arteries, thoracic aorta, aortic valve, and mitral valve. Cardiovascular risk factors and renal function-related parameters (glomerular filtration rate, glomerular filtration rate slope, serum creatinine, serum urea nitrogen, hemoglobin, albumin, calcium, phosphate, and parathyroid hormone) were included in multivariate regression models to predict cardiovascular calcium. Prevalences of calcium deposition at the level of coronary arteries, thoracic aorta, aortic valve, and mitral valve were 69%, 46%, 39%, and 16%, respectively. On multivariate analysis, coronary artery calcium score was predicted by age (p < 0.0001), gender (p = 0.0001), diabetes (p = 0.024), and history of coronary artery disease (p = 0.016), but not by renal function related parameters. Similarly, renal function related parameters were not predictive of aortic or valvular calcium. In conclusion, predialysis CKD is associated with a high prevalence of cardiovascular calcium. The extent of cardiovascular calcium in patients with predialysis CKD is related to some of the traditional risk factors for atherosclerosis but not to indexes of abnormal renal function or progression in renal dysfunction.     

Aggressive versus moderate lipid-lowering therapy in postmenopausal women with hypercholesterolemia: Rationale and design of the Beyond Endorsed Lipid Lowering with EBT Scanning (BELLES) trial

BACKGROUND: Electron beam tomography (EBT) is a noninvasive technique that allows the study of the entire coronary artery tree during a brief imaging session without the injection of any contrast media. Atherosclerosis is identified vicariously through the visualization of coronary calcific deposits. Quantitative assessments of calcium burden, such as calcium volume scores, have been shown to be a useful means to assess treatment-related changes in the extent of atherosclerotic plaques. Historically, the elderly female population has received less medical recognition regarding the risk and severity of coronary heart disease (CHD). METHODS: In the BELLES (Beyond Endorsed Lipid Lowering with EBT Scanning) trial, the presence of asymptomatic CHD in 600 postmenopausal women will be assessed by EBT. In this 1-year, multicenter, randomized, double-blind, parallel-group study, aggressive lipid-lowering treatment will be compared with moderate lipid-lowering treatment in postmenopausal women with hypercholesterolemia. The hypothesis we will test is that aggressive lipid-lowering therapy with 80 mg/d atorvastatin can produce greater reductions in atherosclerotic plaque burden as assessed by volumetric calcium scores than a moderate treatment with 40 mg/d pravastatin. The primary outcome measure will be the percent change from baseline in total CVS determined by EBT at 12 months. CONCLUSIONS: The results of the BELLES trial will help assess the actual incidence of CHD in postmenopausal women and the relative ability of two different lipid-lowering therapies to halt its progression.     

Usefulness of aortic valve calcium scores by electron beam computed tomography as a marker for aortic stenosis

This study was undertaken to determine whether aortic valve calcium (AVC) scores measured by electron beam tomography can identify patients with echocardiographically defined aortic stenosis. Electron beam tomography is increasingly being used to detect coronary artery calcium. AVC can also be measured on electron beam tomographic (EBT) scans obtained to screen for coronary calcium. Whether EBT AVC scores correlate with the presence of aortic stenosis, as assessed by echocardiography, is unknown. Results of this study suggest that AVC scores should be calculated routinely for coronary calcium screening EBT scans, and that patients with Agatston AVC scores above a certain level (e.g., >150) should be referred for echocardiography.     

Renal artery calcium: relationship to systemic calcified atherosclerosis

In this study we tested the hypothesis that calcium due to atherosclerosis in the renal arteries would be significantly associated with calcium in multiple other vascular beds, independent of traditional risk factors for cardiovascular disease (CVD). Electron beam computed tomography was conducted in 1461 consecutive asymptomatic patients free of clinical CVD to determine the presence and extent of calcium in the renal arteries, coronary and non-coronary vasculature and the aortic and mitral annuli. The overall prevalence for calcium in either renal artery was 18.0%, with men having a significantly higher prevalence (20.2%) than women (15.0%) [p = 0.01]. Renal artery calcium (RAC) was significantly correlated with calcium located in the carotids, coronaries, thoracic aorta, abdominal aorta and iliac arteries and calcium in the mitral and aortic annuli (r range = 0.22-0.37). In a multi-variable model containing the traditional CVD risk factors, the presence of calcium in the renal arteries was significantly associated with age, male sex and a diagnosis of hypertension. After adjustment for these variables, the presence of calcium in the thoracic or abdominal aorta was significantly associated with RAC (OR = 2.1 and 2.0, respectively; p < 0.01 for both). The sensitivity for prevalent RAC was highest in those individuals with any calcium in the abdominal aorta (94.5%). In conclusion, calcium related to atherosclerosis in the renal arteries is highly associated with atherosclerotic calcification in other vascular beds, especially the aorta, and the valvular annuli. These relationships are independent of traditional CVD risk factors.     

Valvular calcification in hemodialysis patients randomized to calcium-based phosphorus binders or sevelamer

BACKGROUND AND AIM OF THE STUDY: Valvular calcification is common in patients with end-stage renal disease, and is associated with an unfavorable prognosis. It was hypothesized that sevelamer, a non-calcium-based phosphorus binder, might attenuate the progression of valvular calcification. METHODS: Two hundred subjects on maintenance hemodialysis received either sevelamer or calcium-based phosphorus binders. To assess the extent of calcification, 186 subjects underwent baseline electron beam tomography (EBT) of the coronary arteries, aorta and mitral and aortic valves, and 132 had follow up EBT scans at week 52. Changes in valvular calcification and combined valvular/vascular calcification were monitored and compared. RESULTS: At baseline, mitral valve calcification was seen in 46% of subjects, aortic valve calcification in 33%. Most subjects with zero values at baseline failed to progress over one year. Aortic valve calcification was significantly increased in calcium-treated subjects. Changes in mitral valve calcification, and combined mitral + aortic valve calcification were less in sevelamer-treated than in calcium-treated subjects, but not significantly so. When combining valvular and vascular calcification, the median (10%, 90%) change in sevelamer-treated subjects was significantly lower than in calcium-treated subjects (6, -5084 to 1180 versus 81, -1150 to 2944, p = 0.04). The effect of sevelamer remained significant after adjustment for baseline calcification and the time-averaged calcium-phosphorus product, and was independent of the calcium preparation (acetate versus carbonate), geographic region (US versus Europe), LDL- or HDL-cholesterol, C-reactive protein and statin use. Significantly more sevelamer-treated subjects experienced an arrest (45 versus 28%, p = 0.047) or regression (26 versus 10%, p = 0.02) in total valvular and vascular calcification. CONCLUSION: Sevelamer arrested the progression of valvular and vascular calcification in almost 50% of hemodialysis subjects. Sevelamer treatment, plus intensive control of calcium and phosphorus levels, may attenuate progression of, or achieve regression in, cardiac valvular calcification.     

Relationship between premenopausal dietary intake and postmenopausal subclinical atherosclerosis

OBJECTIVES: This study examines the association of premenopausal dietary intake with postmenopausal subclinical atherosclerosis. DESIGN: A prospective population-based cohort of 401 premenopausal women from the Healthy Women Study. Baseline premenopausal dietary intake was determined with the use of single 24-h recall. Coronary and aortic calcium scores were measured by electron beam computed tomography 8 years after menopause, and carotid plaque index was measured by carotid ultrasound scan 5 years after menopause. RESULTS: Prevalence of coronary, aortic, and carotid subclinical atherosclerosis were 47.3%, 75.4%, and 52.1%, respectively. In unadjusted analysis, the relative risks (RR) of saturated fat intake for coronary calcification in second, third and highest quartile groups compared to the lowest were 1.82 (95% confidence interval, 1.00-3.30), 1.49 (0.82-2.70), and 1.99 (1.09-3.62), while those of carbohydrate intake were 0.48 (95% confidence interval, 0.26-0.88), 0.47 (0.26-0.86), and 0.35 (0.19-0.64), respectively. None of the dietary components were significantly associated with aortic calcification or carotid plaque. CONCLUSION: The association between premenopausal dietary intake and postmenopausal subclinical atherosclerosis supports the recommended premenopausal dietary intervention for the prevention of cardiovascular disease.     

Plasma homocysteine predicts progression of atherosclerosis

MINI ABSTRACT: Three emerging risk factors potentially useful in predicting future cardiac events are electron-beam computed tomography (EBT), homocysteine(HCY), and C-reactive Protein (CRP). We evaluated a cohort of 133 serial asymptomatic patients, who underwent two consecutive EBT scans (8-84 months apart) and a comprehensive cardiac risk factor assessment, including measurements for lipids, ultrasensitive CRP and homocysteine. Individuals with elevated HCY (> or =12 micromol/L) demonstrated a mean increase in CC progression of 35% per year, while those with HCY <12 micromol/L (median) progressed at 17% per year (p = 0.0008). Patients with a level equal to or lower than the median value of CRP (0.8 mg/L) had a median yearly progression of 22%, compared to 21% for those with CRP value = 0.9-11 mg/L (p = ns). Presence of elevated HCY (>12 micromol/L) strongly and independently predicts progression of coronary plaque burden. BACKGROUND: Despite the availability of effective preventive therapies, coronary artery disease (CAD) remains the leading cause of morbidity and mortality. Use of traditional cardiovascular risk factors is imprecise and predicts less than one half of future cardiovascular events. Three 'emerging risk factors', as potential means of identifying subclinical atherosclerosis and predicting future cardiovascular events, are electron-beam computed tomography, homocysteine, and C-reactive protein. Given the evidence that HCY and CRP are involved in atherogenesis, we hypothesized that significant progression of EBT calcium score (a measure of atherosclerotic plaque burden) is associated with higher levels of these markers. METHODS: We evaluated 133 asymptomatic patients (100 men, 33 women; mean age was 61 +/- 9 years) who underwent previous EBT calcium score testing at Harbor-UCLA 8-80 months prior to enrollment (mean follow-up 20 months). Exclusion criteria included those with known or symptomatic CAD and chronic renal disease. During enrollment, we measured risk factors, serum HCY, serum lipids, ultrasensitive-CRP, and repeat EBT calcium scan. Statistical analysis was performed using probable Chi square method, and Student's t-test. RESULTS: Individuals with elevated HCY (> or =12 micromol/L) demonstrated a mean increase in CC progression of 35% per year, while those with HCY <12 micromol/L (median) progressed at 17% per year (p = 0.0008). Patients with a level equal to or lower than the median value of CRP (0.8 mg/L) had a median yearly progression of 22%, compared to 21% for those with CRP value = 0.9-11 mg/L (p = ns). Neither cholesterol values, body mass index, gender, age nor presence of individual risk factors predicted progression of coronary calcium. CONCLUSION: Presence of elevated HCY (>12 micromol/L) strongly and independently predicts progression of coronary plaque burden.     

The association between angiotensin-converting enzyme gene polymorphism and coronary calcification. The Rotterdam Coronary Calcification Study

BACKGROUND: An insertion/deletion (I/D) polymorphism in the gene encoding angiotensin-converting enzyme (ACE) has been associated with serum ACE levels. The association between the ACE I/D polymorphism and coronary heart disease is unclear. Electron-beam-computed tomography (EBT) is a technique to non-invasively quantify the amount of coronary calcification. We investigated the association between the ACE I/D polymorphism and coronary calcification. METHODS AND RESULTS: The Rotterdam Coronary Calcification Study is a population-based study in subjects aged 55 years and over. EBT scanning was performed in 2013 participants. Coronary calcification was quantified according to the Agatston score. The ACE I/D polymorphism was available for 1976 subjects. Geometric mean calcium scores in men with the II, ID and DD genotype were 167, 207 and 219, respectively. However, the difference in calcium score (p=0.19 for ID versus II; p=0.15 for DD versus II) and the trend (ptrend=0.17) were not significant. Calcium scores in women with the II, ID and DD genotype were 44, 42 and 36, respectively. There were no significant differences in calcium score (p=0.78 for ID versus II; p=0.29 for DD versus II), neither was the trend (ptrend=0.27). After we stratified on cardiovascular risk factors, no associations were present. CONCLUSION: The present study failed to show an association between the ACE I/D polymorphism and coronary calcification in the general population. Also, no significant associations were present between the ACE I/D polymorphism and coronary calcification in strata of cardiovascular risk factors.     

Valvular and thoracic aortic calcium as a marker of the extent and severity of angiographic coronary artery disease

Background

The presence of calcified extracoronary structures as a useful indicator of underlying coronary artery disease (CAD) has not yet been established. The purpose of this study was to evaluate whether valvular and thoracic aortic calcification is associated with obstructive CAD.

Methods

We evaluated 99 patients who underwent both coronary angiography and electron beam tomography (EBT) coronary scanning. We identified the presence, absence, and amount of calcification in the aortic valve (AVC), mitral annulus (MAC), descending aorta (DAC), and ascending aorta (AAC). The extent of CAD was graded according to the number of vessels diseased (VD).

Results

Patients with multivessel disease (MVD) had a higher proportion of DAC. The presence of DAC significantly increased the specificity of EBT to detect CAD (58% with a calcium score >0 to 88% for calcium score>0 and DAC >0, P < .001). Both AAC and DAC were associated with a significantly higher rate of MVD in women (DAC, 63% in MVD vs 19% without, P < .01.; AAC, 65% vs 22%, P < .05). MAC had no relationship to either stenosis severity or the presence of obstructive CAD. AVC was the strongest predictor of the severity of CAD and predicted the presence of 3-vessel disease.

Conclusion

AVC and thoracic aortic calcification as detected with EBT are associated with the angiographic extent and severity of CAD and add incremental diagnostic value to the coronary artery calcium score. MAC does not add incremental value. (Am Heart J 2003;145:xxx-xxx.)     

Comparison of spiral and electron beam tomography in the evaluation of coronary calcification in asymptomatic persons

Recently, investigators have begun evaluating the ability of spiral computed tomography (sequence scan mode-SEQ) to measure coronary calcium. Electron Beam Tomography (EBT) and SEQ studies were performed in 10 women and 23 men, with a mean age of 54+/-9 years. The EBT study was performed within 4 weeks (mean 11+/-4 days) of the SEQ with no clinical interval event (MI, revascularization). The mean EBT calcium score (Agatston method) was 52.1+/-58.6, with a range of 0 to 175. The SEQ mean score was 60.1+/-71.1 (range 0 to 253). There were 7 persons with scores of 0 on both scans, and 9 persons with scores of zero on either EBT or spiral CT, but not both. Three persons had negative EBT studies where SEQ detected calcium, and 6 persons had EBT detected calcium and negative SEQ studies. The six patients with negative SEQ and positive EBT studies had a mean score of 47+/-25.7 (range 9 to 99). The remaining sixteen persons had coronary calcium detected on both studies. As compared to EBT, spiral CT had a sensitivity of 74% and a specificity of 70%, for an overall diagnostic accuracy of 73%. The positive and negative predictive values were 85 and 54%, respectively for SEQ in this study. The absolute difference in scores between the two tests was 29.1+/-28.5 (mean+/-S.D.). The inter-test variability, defined as the mean values of the differences between the calcium scores in the two scans on the same subjects divided by the mean of the two scores (Absolute Difference between tests/mean), was 84.5% in this study. In asymptomatic persons, spiral CT (using SEQ) provides a limited sensitivity (74%) and specificity (70%) for coronary calcium when compared to EBT. Caution should be used when evaluating the results of spiral CT coronary calcium especially in patients with relatively low calcium scores (<200).     

Clinical use of coronary calcium scanning with computed tomography

EBT has undergone rigorous testing for reliability and validity of CAC measurements, and has been proven to be useful in identifying individuals with, or at risk for, coronary heart disease. Although MDCT is a promising tool for coronary calcium scoring, more studies are needed that compare EBT and MDCT scans in the same patients, especially with calcium scores of less than 100. Further radiation dose reduction strategies for MDCT are currently being evaluated. MDCT studies of progression, reproducibility, and outcomes are needed to fully evaluate its potential to measure and serially follow atherosclerosis compared to EBT. Studies examining the benefit of serial coronary calcium scoring to non-invasively assess the progression or regression of coronary calcium are currently underway. EBT is a method that can be used to estimate the overall coronary atherosclerotic plaque burden. It can be used to diagnose the presence and determine the extent of coronary atherosclerosis; furthermore, the calcium score information can be used to assess the likelihood of advanced obstructive disease and to provide prognostic information. Finally, serial CAC measurements by EBT have the potential to determine the efficacy of therapeutic interventions by demonstrating progression, stabilization, or regression of coronary atherosclerotic disease during therapy.     

Intimal estrogen receptor (ER)beta, but not ERalpha expression, is correlated with coronary calcification and atherosclerosis in pre- and postmenopausal women

BACKGROUND: Controversy exists over the association of estrogen and cardiovascular disease. Estrogen receptors (ERs) alpha and beta are expressed in the endothelial cells and vascular smooth muscle cells (VSMCs) of many arteries, but the relative importance of ERalpha or ERbeta in mediating the vascular response to estrogens is not well defined, particularly in humans. We have shown previously that postmenopausal women receiving hormone therapy (HT) had lower mean coronary artery calcium, plaque area, and calcium-to-plaque ratio compared with untreated women. In this study, we examined coronary artery ERalpha and ERbeta expression in pre- and postmenopausal women as a function of plaque area, calcium area, calcium-to-plaque ratio, and estrogen status. METHODS: Coronary arteries were obtained at autopsy from a total of 55 women: nine premenopausal women, 13 postmenopausal women on HT and 33 untreated postmenopausal women (non-HT). Coronary calcification was quantified by contact microradiography, and atherosclerotic plaque area was measured histologically. Coronary artery cross-sections were immunostained for ERalpha and ERbeta, and the amount of receptors was estimated semiquantitatively in each arterial wall layer (intima, adventitia, and media). Double immunofluorescence was used to colocalize ERalpha and ERbeta with smooth muscle actin, a marker of VSMCs. RESULTS: ERbeta and ERalpha were expressed in all artery wall layers, but most avidly in the media (P = 0.001), and colocalized with VSMCs. ERbeta expression exceeded ERalpha expression in all wall layers (P < 0.001) and was adjacent to areas of calcium deposition. ERbeta expression in the intimal layer correlated with calcium content, plaque area, and calcium-to-plaque ratio (all P < 0.01) and tended to be greater in non-HT than in HT women (P = 0.06). ERalpha expression did not vary significantly among groups, nor did it correlate with calcium content, plaque area or calcium-to-plaque ratio. Expression of ERalpha but not ERbeta declined with age (P < 0.01) in HT women only. Age had no effect on ERalpha or ERbeta expression in non-HT or premenopausal women. CONCLUSIONS: ERbeta is the predominant ER in human coronary arteries and correlates with coronary calcification, a marker of severe atherosclerosis. Increased ERbeta expression is linked to advanced atherosclerosis and calcification independent of age or hormone status. Future pharmacogenetic studies that target this receptor are needed to confirm causality.     

Association of aortic valve calcium detected by electron beam computed tomography with echocardiographic aortic valve disease and with calcium deposits in the coronary arteries and thoracic aorta

We conducted electron beam computed tomographic (EBCT) testing in a representative sample of 327 Framingham Heart Study subjects without clinical cardiovascular disease. EBCT was compared with 2-dimensional echocardiography for the detection of degenerative aortic valve (AV) disease. We determined the association between EBCT measures of AV calcium and calcium deposits in the coronary arteries and thoracic aorta. Of 327 subjects (mean age 60 +/- 9 years; 51% men), 14% had EBCT AV calcium (median Agatston score 0, range 0 to 1,592). The prevalence of AV calcium increased predictably across decades of age. Compared with echocardiography, the sensitivity and specificity of EBCT for the detection of degenerative AV disease were 24% and 94%, respectively. In unadjusted logistic regression models, the prevalence of EBCT AV calcium increased across tertiles of coronary artery calcium (for trend across tertiles, odds ratio [OR] 2.2, 95% confidence interval [CI] 1.4 to 3.5) and thoracic aorta calcium (for trend OR 2.8, 95% CI 1.7 to 4.4). After adjustment for age and gender, the associations of AV calcium with coronary calcium and thoracic aorta calcium were attenuated and no longer statistically significant. Thus, compared with echocardiography, EBCT was specific but insensitive for the detection of degenerative AV disease. EBCT AV calcium was associated with calcium deposits in the coronary arteries and the thoracic aorta, but these associations were confounded by age and risk factors.     

Pulse pressure is an independent predictor for the progression of aortic wall calcification in patients with controlled hyperlipidemia

Recent epidemiological studies suggested that calcifications of the aorta and the coronary arteries are important predictors for cardiovascular morbidity and mortality. However, the relation between blood pressure components and the progression of vascular wall calcification has remained unclear. We quantified calcium deposits in the abdominal aorta as the percentage of aortic calcification volume (%ACV) using computed tomography in patients with hyperlipidemia. Those who had aortic calcification were treated with lipid-lowering agents and followed-up for >2 years (6.3+/-3.2 years). The relationship between the components of blood pressure and the increase in %ACV per year (Delta%ACV/year) was assessed in subjects in whom serum lipid levels were well controlled during the follow-up periods. An age- and sex-adjusted correlation analysis showed that Delta%ACV/year was significantly correlated to body mass index (r=0.229, P=0.015), systolic blood pressure (r=0.244, P=0.009), and pulse pressure (r=0.359, P<0.001). A multivariate regression analysis revealed that pulse pressure is an independent and the most sensitive predictor for Delta%ACV/year (beta=0.389, P<0.001) among the blood pressure components. These results suggested that increase in pulse pressure promotes the progression of vascular calcification.