Eisenmenger Syndrome Among Children with Unrepaired Congenital Heart Defects in Yunnan, China.

Eisenmenger syndrome is a life-threatening complication of congenital heart defects (CHD). Since Eisenmenger syndrome among children of repaired CHD is rare, very few studies have had the necessary data to investigate its distribution in children. The current study used data collected in rural China to investigate the prevalence of Eisenmenger syndrome in children with unrepaired CHD. Data were from the 2006 to 2016 patient medical records of China California Heart Watch, which is a traveling cardiology clinic in Yunnan Province, China. Patients were included if they (1) aged 18 or below, (2) had CHD(s), and (3) the defect was not repaired by the time of the clinic visit. The prevalence of Eisenmenger syndrome was calculated in each age and defect group. Using logistic regression models, we tested whether oxygen saturation, Down syndrome, sex, and age were significantly associated with Eisenmenger syndrome. Of the 1301 study participants, ventricular septum defect (VSD), atrial septal defect (ASD), and patent ductus arteriosus (PDA) were the most common CHD. About one-sixth of the patients had pulmonary hypertension and 1.5% had Eisenmenger syndrome. The percentages of Eisenmenger syndrome were 1.8% in VSD patients, 0 in ASD patients, and 0.9% in PDA patients. Patients in the age group between 15 and 18 years had the highest percentages of Eisenmenger syndrome (11.5%). Age and presence of Down syndrome were significantly associated with the presence of Eisenmenger syndrome. Our finding highlights the importance of early detection and correction of CHD.

Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).

Aims: While coronary artery calcium (CAC) has been extensively validated for predicting clinical events, most outcome studies of CAC have evaluated coronary heart disease (CHD) rather than atherosclerotic cardiovascular disease (ASCVD) events (including stroke). Also, virtually all CAC studies are of short- or intermediate-term follow-up, so studies across multi-ethnic cohorts with long-term follow-up are warranted prior to widespread clinical use. We sought to evaluate the contribution of CAC using the population-based MESA cohort with over 10 years of follow-up for ASCVD events, and whether the association of CAC with events varied by sex, race/ethnicity, or age category. Methods and results: We utilized MESA, a prospective multi-ethnic cohort study of 6814 participants (51% women), aged 45-84 years, free of clinical CVD at baseline. We evaluated the relationship between CAC and incident ASCVD using Cox regression models adjusted for age, race/ethnicity, sex, education, income, cigarette smoking status, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diabetes, lipid-lowering medication, systolic blood pressure, antihypertensive medication, intentional physical exercise, and body mass index. Only the first event for each individual was used in the analysis. Overall, 500 incident ASCVD (7.4%) events were observed in the total study population over a median of 11.1 years. Hard ASCVD included 217 myocardial infarction, 188 strokes (not transient ischaemic attack), 13 resuscitated cardiac arrest, and 82 CHD deaths. Event rates in those with CAC = 0 Agatston units ranged from 1.3% to 5.6%, while for those with CAC > 300, the 10-year event rates ranged from 13.1% to 25.6% across different age, gender, and racial subgroups. At 10 years of follow-up, all participants with CAC > 100 were estimated to have >7.5% risk regardless of demographic subset. Ten-year ASCVD event rates increased steadily across CAC categories regardless of age, sex, or race/ethnicity. For each doubling of CAC, we estimated a 14% relative increment in ASCVD risk, holding all other risk factors constant. This association was not significantly modified by age, sex, race/ethnicity, or baseline lipid-lowering use. Conclusions: Coronary artery calcium is associated strongly and in a graded fashion with 10-year risk of incident ASCVD as it is for CHD, independent of standard risk factors, and similarly by age, gender, and ethnicity. While 10-year event rates in those with CAC = 0 were almost exclusively below 5%, those with CAC ≥ 100 were consistently above 7.5%, making these potentially valuable cutpoints for the consideration of preventive therapies. Coronary artery calcium strongly predicts risk with the same magnitude of effect in all races, age groups, and both sexes, which makes it among the most useful markers for predicting ASCVD risk.

Risk and the physics of clinical prediction.

The current paradigm of primary prevention in cardiology uses traditional risk factors to estimate future cardiovascular risk. These risk estimates are based on prediction models derived from prospective cohort studies and are incorporated into guideline-based initiation algorithms for commonly used preventive pharmacologic treatments, such as aspirin and statins. However, risk estimates are more accurate for populations of similar patients than they are for any individual patient. It may be hazardous to presume that the point estimate of risk derived from a population model represents the most accurate estimate for a given patient. In this review, we exploit principles derived from physics as a metaphor for the distinction between predictions regarding populations versus patients. We identify the following: (1) predictions of risk are accurate at the level of populations but do not translate directly to patients, (2) perfect accuracy of individual risk estimation is unobtainable even with the addition of multiple novel risk factors, and (3) direct measurement of subclinical disease (screening) affords far greater certainty regarding the personalized treatment of patients, whereas risk estimates often remain uncertain for patients. In conclusion, shifting our focus from prediction of events to detection of disease could improve personalized decision-making and outcomes. We also discuss innovative future strategies for risk estimation and treatment allocation in preventive cardiology.

Progression of coronary calcium and incident coronary heart disease events: MESA (Multi-Ethnic Study of Atherosclerosis).

OBJECTIVES: The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events. BACKGROUND: CAC predicts CHD events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. METHODS: We studied 6,778 persons (52.8% female) aged 45 to 84 years from the MESA (Multi-Ethnic Study of Atherosclerosis) study. A total of 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n = 1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max = 9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HRs) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors. RESULTS: A total of 343 and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 Agatston units. Among persons without CAC at baseline (n = 3,396), a 5-unit annual change in CAC was associated with an adjusted HR (95% Confidence Interval) of 1.4 (1.0 to 1.9) for total and 1.5 (1.1 to 2.1) for hard CHD. Among those with CAC >0 at baseline, HRs (per 100 unit annual change) were 1.2 (1.1 to 1.4) and 1.3 (1.1 to 1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HRs of 3.8 (1.5 to 9.6) for total and 6.3 (1.9 to 21.5) for hard CHD compared to those without progression. CONCLUSIONS: Progression of CAC is associated with an increased risk for future hard and total CHD events.

High blood pressure in Chinese ethnic minorities: report from rural Yunnan province.

BACKGROUND: Hypertension (HTN) is a growing cause of morbidity and mortality among rural Chinese. While HTN has been studied in various regions of China, little is known about HTN among ethnic minorities in rural China. METHODS: A total of 36 villages were randomly selected from Yunnan province, China. From these villages, a total of 1,676 subjects from 10 ethnic minorities and the Han ethnic majority were selected for interview and blood pressure (BP) measurement. From each village, 50-80 men and women between the ages of 50 and 70 years were randomly selected. HTN prevalence, treatment, and control rates of HTN were evaluated in these 11 ethnic groups. RESULTS: After controlling for age, gender, body mass index (BMI), smoking, alcohol, and monosodium glutamate intake, prevalence of HTN varied between 25% in the Hani minority and 64% in the Tibetan minority (P < 0.001). Treatment rates varied between 0% in the Hani minority and 41% in the Tibetan minority (P = 0.006). Control rates varied between 0% in the Hani minority and 17% in the Tibetan minority (P = 0.28). Prevalence, treatment, and control rates in the Han ethnic group were 35, 22, and 12%, respectively. CONCLUSIONS: The prevalence of HTN varies widely among China's ethnic groups. Treatment and control rates of HTN also vary and are inadequate in the minority ethnic groups as well as in the Han majority.

Postprocedural outcomes of rural children undergoing correction of congenital heart lesions in Yunnan Province, China.

The management of congenital heart disease (CHD) remains a significant challenge in developing regions. Since 2006, China California Heart Watch has provided cardiac services in China's Yunnan province. Our Grants for Kids program aims to diagnose and fund surgical and nonsurgical treatments for underprivileged children with congenitally malformed hearts. This report analyzes our patient outcomes. From 2007 to 2010, 36 children with CHD underwent either surgical or percutaneous procedures at local Chinese medical centers, and 94% of our patients could be contacted for follow-up assessment. The mortality and complication rates of our patient population compare favorably with international data. Our study provides a model through which networking with local hospitals and regional cardiac centers can be an effective way to assist developing areas in providing cardiac care to rural underserved populations.

Abdominal aortic calcium and multi-site atherosclerosis: the Multiethnic Study of Atherosclerosis.

BACKGROUND: Abdominal aortic calcification (AAC) is a measure of subclinical cardiovascular disease (CVD). Data are limited regarding its relation to other measures of atherosclerosis. METHODS: Among 1812 subjects (49% female, 21% black, 14% Chinese, and 25% Hispanic) within the population-based Multiethnic Study of Atherosclerosis, we examined the cross-sectional relation of AAC with coronary artery calcium (CAC), ankle brachial index (ABI), and carotid intimal medial thickness (CIMT), as well as multiple measures of subclinical CVD. RESULTS: AAC prevalence ranged from 34% in those aged 45-54 to 94% in those aged 75-84 (p < 0.0001), was highest in Caucasians (79%) and lowest in blacks (62%) (p < 0.0001). CAC prevalence, mean maximum CIMT ≥ 1mm, and ABI < 0.9 was greater in those with vs. without AAC: CAC 60% vs. 16%, CIMT 38% vs. 7%, and ABI 5% vs. 1% for women and CAC 80% vs. 37%, CIMT 43% vs. 16%, and ABI 4% vs. 2% for men (p < 0.01 for all except p < 0.05 for ABI in men). The substantially greater prevalence for CAC in men compared to women all ages is not seen for AAC. By age 65, 97% of men and 91% of women have AAC, CAC, increased CIMT, and/or low ABI. The presence of multi-site atherosclerosis (≥ 3 of the above) ranged from 20% in women to 30% in men (p < 0.001), was highest in Caucasians (28%) and lowest in Chinese (16%) and ranged from 5% in those aged 45-54 to 53% in those aged 75-84 (p < 0.01 to p < 0.001). Finally, increased AAC was associated with 2-3-old relative risks for the presence of increased CIMT, low ABI, or CAC. CONCLUSIONS: AAC is associated with an increased likelihood of other vascular atherosclerosis. Its additive prognostic value to these other measures is of further interest.

Subclinical atherosclerosis in northern and southern China: the Chinese paradox.

BACKGROUND: The incidence of coronary heart disease (CHD) is higher in Northern than that in Southern China, however differences in traditional CHD risk factors do not fully explain this. No study has examined the differences in subclinical atherosclerosis that may help explain the differences in incidence. This study examined these differences in subclinical atherosclerosis using coronary computed tomography (CT) for calcification between the Northern and Southern China. METHODS: We selected a random sample of participants in a large multi-center ongoing epidemiologic study for coronary calcium scanning in one northern city (North) (Beijing, n = 49) and in two southern cities (South) (Shanghai, n = 50, and Guangzhou, n = 50). Participants from the three field centers (mean age 67 years) underwent coronary risk factor evaluation and cardiac CT scanning for coronary calcium measurement using the Multi-Ethnic Study of Atherosclerosis scanning protocol. RESULTS: Adjusted log-transformed coronary artery calcium score in North China (Beijing) was 3.1 ± 0.4 and in South China (Shanghai and Guangzhou) was 2.2 ± 0.3 (P = 0.04). Mean calcium score for the northern city of Beijing was three times higher than that of the southern city of Guangzhou (P = 0.01) and 2.5 times higher than for the southern city of Shanghai (P = 0.03). CONCLUSIONS: The extent of subclinical atherosclerosis is significantly higher in the northern city of Beijing than that in the two southern cities of Guangzhou and Shanghai, even after adjusting for standard cardiac risk factors. This finding suggests that standard risk factors do not fully explain north south differences in clinical CHD incidence.

The farther from town the lower the blood pressure: report from rural Yunnan province.

BACKGROUND: Hypertension (HTN) is a major cause of death in Chinese farmers. Remoteness from population centers may independently affect HTN prevalence and severity. METHODS: We used random cluster sampling to select 27 villages in Yunnan province, China. Within each village, we randomly selected 50-80 men and women between the ages of 50 and 70 years. A total of 1,177 participants underwent interviews and blood pressure (BP) measurement. We evaluated the relationship between BP and distance of the participants' village from the town and county centers with and without adjustment for covariates. RESULTS: There was a significant (P < 0.001) inverse relationship between BP and distance from populations centers. For every 10 km from the town center, the mean systolic BP (SBP) in the village decreased by 1.2 mm Hg and the mean diastolic by 0.5 mm Hg. After adjustment for age, gender, ethnicity, body mass index, smoking, and drinking, we found that SBP decreased by 1.8 mm Hg (P = 0.03) and diastolic BP by 1.0 mm Hg (P = 0.02) for every 10 km distance from the town center. CONCLUSIONS: HTN prevalence and severity are significantly linked to distance from population centers in rural Chinese farmers. The farther a farmer's village is from larger population centers, the greater is the probability that his/her BP will be normal. This relationship is independent of age, gender, ethnicity, body mass index, smoking, and alcohol use. Strategies in addressing HTN in rural regions should take account of this geographic dependence on distance from population centers.

Does coronary calcium score predict future cardiac function? Association of subclinical atherosclerosis with left ventricular systolic and diastolic dysfunction at MR imaging in an elderly cohort.

PURPOSE: To evaluate subclinical atherosclerosis measured by using coronary artery calcium (CAC) as a predictor of future left ventricular (LV) systolic and diastolic function in asymptomatic elderly participants. MATERIALS AND METHODS: The institutional review boards of the University of Southern California and the Harbor University of California Los Angeles Research and Education Institute (where the South Bay Heart Watch study was initially conducted) approved this HIPAA-compliant study of 386 participants (mean age, 75.2 years) from among the original 1461 participants in the longitudinal South Bay Heart Watch prospective investigation of subclinical atherosclerosis. CAC at computed tomography was correlated with LV ejection fraction (LVEF), regional wall motion abnormalities (RWMAs), and peak filling rate (PFR) assessed a mean of 11.4 years ± 0.6 (standard deviation) later with cardiac magnetic resonance imaging. Analysis of variance and covariance testing was performed with the Wald test, testing for trends across the CAC groups. Covariates included age, level of total cholesterol, level of high-density lipoprotein cholesterol, systolic blood pressure, use of lipid-lowering medication, and smoking status. RESULTS: Mean LVEF was 60.3% ± 9.9, with 11 (2.8%) of 386 participants having an LVEF of less than 40%. Forty-six (11.9%) of 386 participants had RWMAs. Higher CAC scores were associated with slightly lower LVEF (P for trend = .04) and a greater percentage of participants with decreased PFR (P for trend = .47) and RWMAs (P for trend = .01). After age- and risk factor-adjustment, only RWMA (P = .05) was associated with higher CAC. RWMAs were associated with significantly (P < .001) lower mean LVEF and PFR. Nineteen (41%) of 46 participants with RWMAs had documented Q-wave myocardial infarction, and three (7%) underwent coronary revascularization. CAC scores of 100 or greater were associated with a 2.2-fold (95% confidence interval: 1.30, 3.75) increase in RWMA (P < .001). CONCLUSION: Subclinical atherosclerosis assessed by using CAC is associated with an increased future likelihood of RWMA, as a marker of previous and possible subclinical coronary artery disease.

Association of electrocardiographic abnormalities with coronary artery calcium and carotid artery intima-media thickness in individuals without clinical coronary heart disease (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Isolated minor nonspecific ST-segment and T-wave abnormalities (NSSTAs), minor and major electrocardiographic (ECG) abnormalities are established, independent risk markers for incident cardiovascular events. Their association with subclinical atherosclerosis has been postulated but is not clearly defined. The aim of this study was to define the association between ECG abnormalities and measurements of subclinical atherosclerosis. We studied participants from MESA, a multiethnic sample of men and women 45 to 84 years of age and free of clinical cardiovascular disease at enrollment. Baseline examination included measurement of traditional risk factors, 12-lead electrocardiograms at rest, coronary artery calcium (CAC) measurement, and common carotid intima-media thickness (CC-IMT). Electrocardiograms were coded using Novacode criteria and were defined as having minor abnormalities (e.g., minor NSSTTAs, first-degree atrioventricular block, and QRS-axis deviations) or major abnormalities (e.g., pathologic Q waves, major STTAs, significant dysrhythmias, and conduction system delays). Multivariable logistic and linear regressions were used to determine cross-sectional associations of ECG abnormalities with CAC and CC-IMT. Of 6,710 participants, 52.7% were women, with a mean age of 62 years. After multivariable adjustment, isolated minor STTAs and minor and major ECG abnormalities were not associated with presence of CAC (>0) in men (odds ratio 1.04, 95% confidence interval 0.81 to 1.33; 1.10, 0.91 to 1.32; and 1.03, 0.81 to 1.31, respectively) or women (1.01, 0.82 to 1.24; 1.04, 0.87 to 1.23; and 0.94, 0.73 to 1.22, respectively). Lack of association remained consistent when using log CAC and CC-IMT as continuous variables. In conclusion, ECG abnormalities are not associated with markers of subclinical atherosclerosis in a large multiethnic cohort.

Association of blood pressure with left ventricular mass in untreated hypertensives in rural Yunnan Province.

BACKGROUND: Chinese rural residents make up one-eighth of the world's population. Hypertension (HTN) and its resultant cardiovascular complications are rapidly increasing in this vast segment of humanity, while its treatment and control remain unacceptably low. HTN is associated with increased left ventricular mass (LVM), but the magnitude and characteristics of this relationship in persons not undergoing treatment are unknown. METHODS: We studied 344 randomly selected adults who were not being treated for HTN and who had ages between 50 and 70 years (mean age 57.8, 51.7% female) using a questionnaire, height, weight, blood pressure (BP), and ultrasonic measurements of LVM. We performed bivariate and multivariable regression analysis to examine the relation of BP with LVM index (LVMI). RESULTS: We found a HTN prevalence of 30%. There was a significant (P < 0.0001) linear relationship between BP and LVMI in this untreated population. Diastolic (DBP) compared to systolic BP (SBP) was more strongly associated with LVMI (beta = 0.714 vs. 0.379, both P = 0.02). Persons with vs. without HTN had higher LVMI (102.5 g vs. 84.9 g, P < 0.0001). CONCLUSIONS: The LVMI of hypertensives, not undergoing treatment in rural Yunnan province is strongly related to BP, especially DBP.

Reproducibility of coronary artery calcified plaque with cardiac 64-MDCT: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: The Multi-Ethnic Study of Atherosclerosis is a longitudinal study evaluating determinants of future cardiac events and progression of atherosclerosis. Emerging data are showing that coronary artery calcification (CAC) is a robust independent predictor of future cardiac events and that measurement of progression depends on reproducibility of the measure. Reproducibility previously was reported on baseline scans obtained with both electron-beam tomography (EBT) and MDCT. The aim of this study was to compare the interscan variability for both Agatston and volume scores derived with newer (16- and 64-MDCT) scanners with that derived with older scanners in the Multi-Ethnic Study of Atherosclerosis. SUBJECTS AND METHODS: The participants in this study were 4,054 persons who underwent dual scanning with EBT (n = 1,716), 4-MDCT (n = 370), 16-MDCT (n = 1,245), or 64-MDCT (n = 723). Agreement on the presence or absence of CAC was assessed with logistic regression models adjusted for age, sex, body mass index, and scanner type. Among participants with CAC, the log-transformed interscan difference was regressed on log-transformed amount of CAC, age, sex, and body mass index. RESULTS: The percentage agreement for the presence or absence of CAC was high and similar across scanner groups (EBT, 16-MDCT, and 64-MDCT). The greatest adjusted average absolute CAC differences between scans were found with the Aquilion 64 (24%; 95% CI, 20.9-27.6) and LightSpeed Pro 16 (19%; 95% CI, 17.4-21.0) scanners, both differences being significantly greater than with the EBT scanner (16%; 95% CI, 15.4-17.5) (p < 0.05). No differences were found between the EBT, Sensation 16, and Sensation 64 scanners. For volume score, the Aquilion 64 was the only scanner with significantly greater average absolute interscan differences than the EBT scanner (p < 0.001). Volume scoring resulted in lower rescan differences for all scanners. CONCLUSION: For CAC scoring, interscan variability with newer-generation MDCT scanners was similar to but not superior to that with the EBT scanner.

Association between non-subcutaneous adiposity and calcified coronary plaque: a substudy of the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Excessive non-subcutaneous fat deposition may impair the functions of surrounding tissues and organs through the release of inflammatory cytokines and free fatty acids. OBJECTIVE: We examined the cross-sectional association between non-subcutaneous adiposity and calcified coronary plaque, a noninvasive measure of coronary artery disease burden. DESIGN: Participants in the Multi-Ethnic Study of Atherosclerosis underwent computed tomography (CT) assessment of calcified coronary plaque. We measured multiple fat depots in 398 white and black participants (47% men, 43% black), aged 47-86 y, from Forsyth County, NC, during 2002-2005, with the use of cardiac and abdominal CT scans. In addition to examining each depot separately, we also created a non-subcutaneous fat index with the standard scores of non-subcutaneous fat depots. RESULTS: A total of 219 participants (55%) were found to have calcified coronary plaque. After adjusting for demographics, lifestyle factors, and height, calcified coronary plaque was associated with a 1 SD increment in the non-subcutaneous fat index [odds ratio (OR): 1.41; 95% CI: 1.08, 1.84], pericardial fat (OR: 1.38; 95% CI: 1.04, 1.84), abdominal visceral fat (OR: 1.35; 95% CI: 1.03, 1.76) but not with fat content in the liver, intermuscular fat, or abdominal subcutaneous fat. The relation between non-subcutaneous fat index and calcified coronary plaque remained after further adjustment for abdominal subcutaneous fat (OR: 1.40; 95% CI: 1.00, 1.94). The relation did not differ by sex and ethnicity. CONCLUSIONS: The overall burden of non-subcutaneous fat deposition, but not abdominal subcutaneous fat, may be a correlate of coronary atherosclerosis.

The association of pericardial fat with calcified coronary plaque.

BACKGROUND: Pericardial fat has a higher secretion of inflammatory cytokines than subcutaneous fat. Cytokines released from pericardial fat around coronary arteries may act locally on the adjacent cells. OBJECTIVE: We examined the relationship between pericardial fat and calcified coronary plaque. METHODS AND PROCEDURES: Participants in the community-based Multi-Ethnic Study of Atherosclerosis (MESA) underwent a computed tomography (CT) scan for the assessment of calcified coronary plaque in 2000/2002. We measured the volume of pericardial fat using these scans in 159 whites and blacks without symptomatic coronary heart disease from Forsyth County, NC, aged 55-74 years. RESULTS: Calcified coronary plaque was observed in 91 participants (57%). After adjusting for height, a 1 s.d. increment in pericardial fat was associated with an increased odds of calcified coronary plaque (odds ratio (95% confidence interval): 1.92 (1.27, 2.90)). With further adjustment of other cardiovascular factors, pericardial fat was still significantly associated with calcified coronary plaque. This relationship did not differ by gender and ethnicity. On the other hand, BMI and height-adjusted waist circumference were not associated with calcified coronary plaque. DISCUSSION: Pericardial fat is independently associated with calcified coronary plaque.

Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Coronary artery calcium (CAC) and carotid intima-media thickness (IMT) are noninvasive measures of atherosclerosis that consensus panels have recommended as possible additions to risk factor assessment for predicting the probability of cardiovascular disease (CVD) occurrence. Our objective was to assess whether maximum carotid IMT or CAC (Agatston score) is the better predictor of incident CVD. METHODS: A prospective cohort study of subjects aged 45 to 84 years in 4 ethnic groups, who were initially free of CVD (n = 6698) was performed, with standardized carotid IMT and CAC measures at baseline, in 6 field centers of the Multi-Ethnic Study of Atherosclerosis (MESA). The main outcome measure was the risk of incident CVD events (coronary heart disease, stroke, and fatal CVD) over a maximum of 5.3 years of follow-up. RESULTS: There were 222 CVD events during follow-up. Coronary artery calcium was associated more strongly than carotid IMT with the risk of incident CVD. After adjustment for each other (CAC score and IMT) and age, race, and sex [corrected], the hazard ratio of CVD increased 2.1-fold (95% confidence interval [CI], 1.8-2.5) for each 1-standard deviation (SD) increment of log-transformed CAC score, vs 1.3-fold (95% CI, 1.1-1.4) for each 1-SD increment of the maximum IMT. For coronary heart disease, the hazard ratios per 1-SD increment increased 2.5-fold (95% CI, 2.1-3.1) for CAC score and 1.2-fold (95% CI, 1.0-1.4) for IMT. A receiver operating characteristic curve analysis also suggested that CAC score was a better predictor of incident CVD than was IMT, with areas under the curve of 0.81 vs 0.78, respectively. CONCLUSION: Although whether and how to clinically use bioimaging tests of subclinical atherosclerosis remains a topic of debate, this study found that CAC score is a better predictor of subsequent CVD events than carotid IMT.

Effect of scanner type on the reproducibility of extracoronary measures of calcification: the multi-ethnic study of atherosclerosis.

RATIONALE AND OBJECTIVES: Cardiac computed tomography (CT) has been used extensively to measure coronary artery calcification. However, extracoronary calcifications, such as aortic valve calcification (AVC), may have independent clinical significance as well. The ability to track calcification is dependent on the reproducibility of the original measurement, and the variability of extracoronary calcification measurements still is unknown. Accurate quantification of calcification of the aortic valve, mitral annulus (MAC), and thoracic aortic (TAC) may be possible by using cardiac CT. METHODS: A total of 1,729 randomly chosen participants (ages 45-84, 53% female, 28% African-American, 36% Caucasian, 11% Chinese, 25% Hispanic) of the Multi-Ethnic Study of Atherosclerosis underwent dual scanning by electron beam CT (EBT) or multidetector CT (MDCT) to assess coronary and extra-coronary calcifications. Two calcium measurement methods--Agatston score (AS) and volume score (VS)--were measured for each scan. Concordance for calcium positivity was assessed among all scans. Mean absolute and relative differences between calcium measures on scans 1 and 2, excluding cases for which both scans had a measure of zero, was modeled by using linear regression to compare variability between scanner types. A repeated measures analysis of variance test was used to compare variability across calcium measures, with mean percentage absolute difference as the outcome measure. RESULTS: Concordances for the presence of calcium between duplicate scans were high and similar for both EBT and MDCT. Concordance was high for all three extracoronary measures, with a kappa statistic of kappa = 0.94-0.96. For all three extracoronary sites, Bland-Altman plots demonstrated excellent agreement, with almost all measures falling within the boundaries of the 95% confidence limits of reproducibility. AVC interscan variability was approximately 8% for both AS and VS, with improved variability for EBT as compared with MDCT. Mitral annular calcification demonstrated slightly lower variability than AVC for both scanner types (approximately 6%), with no significant differences between MDCT and EBT. Of the three extracoronary sites, TAC had the highest variability (10%), with MDCT variability slightly lower than EBT variability (9.3 vs. 10.2%, respectively, P = NS). Agatson and volume scores for each of the three extracoronary sites were similar. CONCLUSIONS: Overall rescan measurement variabilities for extracoronary calcification are low and should not be an impediment to the use of this test for studying progression of extracoronary calcification over time.

Implications of C-reactive protein or coronary artery calcium score as an adjunct to global risk assessment for primary prevention of CHD.

BACKGROUND: C-reactive protein (CRP) or coronary artery calcium (CAC) score have been suggested to identify a higher risk subset of intermediate-risk individuals, who potentially could be considered for more aggressive therapy. In the Multi-Ethnic Study of Atherosclerosis (MESA), we estimated the proportion of intermediate-risk participants whose risk status might change based on additional testing using CRP and/or CAC score. METHODS: Framingham 10-year CHD risk scores (FRS) were calculated and cross tabulations were used to determine the percent of individuals at intermediate-risk by FRS with a CRP >3mg/L and/or CAC score >100 AU. Similar analyses were performed using the gender-specific 75th percentile for CRP and CAC. RESULTS: Of the 30% of participants (N=1450) classified as intermediate-risk by FRS, 30% had a CRP >3mg/L and 33% had a CAC score >100 AU. Among intermediate-risk women, 49% had a CRP >3mg/L compared to 27% of intermediate-risk men (p<0.0001) while the same percent of intermediate-risk women and men (33%) had a CAC score >100 AU. Eleven percent or less of men or women had both a high CRP and CAC score whether conventional or gender-specific cut points were used. When the percent of intermediate-risk individuals with an elevated CRP and/or CAC score in MESA were applied to NHANES III data, over a million intermediate-risk individuals would move to high risk status if CRP or CAC screening directed treatment strategies were uniformly adopted in the U.S. CONCLUSION: There were differences in the number of intermediate-risk individuals reclassified as high risk depending on the screening test used, the cut points selected, and the demographics of the individuals being screened. These data highlight current limitations of broadly using risk markers such as CRP and CAC score in an intermediate-risk population.

Coronary calcium measurements: effect of CT scanner type and calcium measure on rescan reproducibility--MESA study.

PURPOSE: To evaluate the effect of scanner type and calcium measure on the reproducibility of calcium measurements. MATERIALS AND METHODS: This investigation was approved by the institutional review boards of each study site and by the Institutional Review Board of the Los Angeles Biomedical Research Institute. Informed consent for scanning and participation was obtained from all participants. The study was Health Insurance Portability and Accountability Act compliant. The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter observational study of 6814 participants undergoing demographic, risk factor, and subclinical disease evaluations. Coronary artery calcium was measured by using duplicate CT scans. Three study centers used electron-beam computed tomography (CT), and three used multi-detector row CT. Coronary artery calcium was detected in 3355 participants. Three calcium measurement methods-Agatston score, calcium volume, and interpolated volume score-were evaluated. Mean absolute differences between calcium measures on scans 1 and 2, excluding cases for which both scans had a measure of zero, was modeled by using linear regression to compare reproducibility between scanner types. A repeated measures analysis of variance test was used to compare reproducibility across calcium measures, with mean percentage absolute difference as the outcome measure. Rescan reproducibility in relation to misregistrations, noise, and motion artifacts was also examined. Variables were log transformed to create a more normal distribution. RESULTS: Concordance for presence of calcium between duplicate scans was high and similar for both electron-beam and multi-detector row CT (96%, kappa = 0.92). Mean absolute difference between calcium scores for the two scans was 15.8 for electron-beam and 16.9 for multi-detector row CT scanners (P = .06). Mean relative differences were 20.1 for Agatston score, 18.3 for calcium volume, and 18.3 for interpolated volume score (P < .01). Reproducibility was lower for scans with versus those without image misregistrations or motion artifacts (P < .01 for both). CONCLUSION: Electron-beam and multi-detector row CT scanners have equivalent reproducibility for measuring coronary artery calcium. Calcium volumes and interpolated volume scores are slightly more reproducible than Agatston scores. Reproducibility is lower for scans with misregistrations or motion artifacts.

Relation of echocardiographic left ventricular mass, geometry and wall stress, and left atrial dimension to coronary calcium in young adults (the CARDIA study).

We examined the relation of measures of echocardiographic left ventricular mass and geometry with coronary artery calcium (CAC) in 2,724 young adults. After adjustment for other coronary risk factors, left atrial dimension remained associated with the presence of CAC, and among subjects positive for CAC, left ventricular mass, end-systolic stress, and septal and posterior wall thicknesses in diastole remained associated with an increased extent of CAC.