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1.  Progression of Coronary Calcium and Incident Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis 
Coronary artery calcium (CAC) predicts coronary heart disease (CHD) events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. We examined whether progression of CAC is a predictor of future CHD events.
Methods and Results
We studied 6,778 persons (52.8% female) aged 45–84 years from the Multi-Ethnic Study of Atherosclerosis. 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 (HR) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors. 343 total and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 units. Among persons without CAC at baseline (n=3,396), a 5 unit annual change in CAC was associated with an adjusted HR of 1.4 (1.0–1.9) for total and 1.5 (1.1–2.1) for hard CHD. Among those with CAC>0 at baseline HR’s (per 100 unit annual change) were 1.2 (1.1–1.4) and 1.3 (1.1–1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HR’s of 3.8 (1.5–9.6) for total and 6.3 (1.9–21.5) for hard CHD compared to those without progression.
Progression of CAC is associated with an increased risk for future hard and total CHD events.
PMCID: PMC4148074  PMID: 23500326
coronary calcification; atherosclerosis; imaging; coronary heart disease
2.  The association of pericardial fat with calcified coronary plaque 
Obesity (Silver Spring, Md.)  2008;16(8):1914-1919.
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.
We examined the relationship between pericardial fat and calcified coronary plaque.
Participants in the community-based Multi-Ethnic Study of Atherosclerosis underwent a computed tomography scan for the assessment of calcified coronary plaque in 2001/02. 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.
Calcified coronary plaque was observed in 91 participants (57%). After adjusting for height, a one standard deviation 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, body mass index and height-adjusted waist circumference were not associated with calcified coronary plaque.
Pericardial fat is independently associated with calcified coronary plaque.
PMCID: PMC4098129  PMID: 18535554
coronary heart disease; body mass index; waist circumference
3.  Subclinical atherosclerosis in northern and southern China: the Chinese paradox 
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.
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.
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).
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.
PMCID: PMC3390074  PMID: 22783288
coronary calcium; CT scanning; atherosclerosis; epidemiology; China
4.  The association between non-subcutaneous adiposity and calcified coronary plaque: A substudy of the Multi-Ethnic Study of Atherosclerosis 
Excessive non-subcutaneous fat deposition may impair the functions of surrounding tissues and organs through the release of inflammatory cytokines and free fatty acids.
We examined the cross-sectional association between non-subcutaneous adiposity and calcified coronary plaque, a non-invasive measure of coronary artery disease burden.
Participants in the Multi-Ethnic Study of Atherosclerosis underwent CT assessment of calcified coronary plaque. We measured multiple fat depots in 398 white and black participants (47% men and 43% black), ages 47–86 years, from Forsyth County, NC during 2002–2005, using cardiac and abdominal CT scans. In addition to examining each depot separately, we also created a non-subcutaneous fat index using the standard scores of non-subcutaneous fat depots.
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 one standard deviation increment in the non-subcutaneous fat index (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 gender and ethnicity.
The overall burden of non-subcutaneous fat deposition, but not abdominal subcutaneous fat, may be a correlate of coronary atherosclerosis.
PMCID: PMC3282464  PMID: 18779279
5.  Abdominal Aortic Calcium and Multi-Site Atherosclerosis: The Multiethnic Study of Atherosclerosis 
Atherosclerosis  2011;214(2):436-441.
Abdominal aortic calcification (AAC) is a measure of subclinical cardiovascular disease (CVD). Data are limited regarding its relation to other measures of atherosclerosis.
Among 1,812 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.
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 ≥ 1 mm, 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 presence of multi-site atherosclerosis (≥ 3 of the above) ranged from 20% in women and 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 to 3-fold relative risks for the presence of increased CIMT, low ABI, or CAC.
AAC is associated with an increased likelihood of other vascular atherosclerosis. Its additive prognostic value to these other measures is of further interest.
PMCID: PMC3040451  PMID: 21035803
atherosclerosis; calcification; cardiovascular disease; epidemiology
6.  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]) 
The American journal of cardiology  2009;104(8):1086-1091.
Isolated minor non-specific ST-segment and T-wave (NSSTA), 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 is to define the association between ECG abnormalities and measures of subclinical atherosclerosis. We studied participants from MESA, a multi-ethnic sample of men and women aged 45–84 and free of clinical cardiovascular disease at enrollment. Baseline examination included measurement of traditional risk factors, resting 12-lead electrocardiograms, coronary artery calcium (CAC) measurement and common carotid intima-media thickness (CCIMT). Electrocardiograms were coded using Novacode criteria and were defined as having either minor abnormalities (e.g., minor non-specific STTA, first degree atrioventricular block, and QRS axis deviations) or major abnormalities (e.g., pathologic Q waves, major ST-segment and T-wave abnormalities, significant dysrhythmias and conduction system delays). Multivariable logistic and linear regressions were used to determine the cross-sectional associations of ECG abnormalities with CAC and common carotid-IMT. Among 6710 participants, 52.7% were women, with a mean age of 62 years. After multivariable-adjustment, isolated minor STTA, minor and major ECG abnormalities were not associated with the presence of CAC (>0) among men (OR 1.04, 95% CI 0.81–1.33; 1.10, 0.91–1.32; and 1.03, 0.81–1.31, respectively) or women (1.01, 0.82–1.24; 1.04, 0.87–1.23; and 0.94, 0.73–1.22, respectively). Lack of association remained consistent when using both log CAC and CC-IMT as continuous variables. ECG abnormalities are not associated with markers of subclinical atherosclerosis in a large multi-ethnic cohort.
PMCID: PMC2871277  PMID: 19801030
7.  Coronary Artery Calcification Compared with Carotid Intima-Media Thickness in Prediction of Cardiovascular Disease Incidence: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Archives of internal medicine  2008;168(12):1333-1339.
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.
To assess whether maximum carotid IMT or CAC (Agatston Score) is the better predictor of incident CVD.
Design, Setting, Patients
Prospective cohort study of 45–84 year-olds initially free of CVD (n = 6,698) in four ethnic groups, with standardized carotid IMT and CAC measures at baseline, in six field centers of the Multi-Ethnic Study of Atherosclerosis (MESA).
Main Outcome Measure(s)
Incident CVD events (coronary heart disease, stroke, and fatal CVD) over a maximum of 5.3 years of follow-up.
There were 222 CVD events during follow-up. CAC was associated more strongly than carotid IMT with risk of incident CVD. After adjustment for each other and traditional CVD risk factors, the hazard of CVD increased 2.1-fold (95% CI 1.8–2.5) for each standard deviation greater level of log-transformed CAC, versus 1.3-fold (95% CI 1.1–1.4) for each standard deviation greater maximum IMT. For coronary heart disease, the hazard ratios per standard deviation increment were 2.5-fold (95% CI 2.1–3.1) for CAC and 1.2-fold (95% CI 1.0–1.4) for IMT. An ROC analysis also suggested that CAC predicted incident CVD better than IMT did.
Although whether and how to clinically use bio-imaging tests of subclinical atherosclerosis remains a topic of debate, this study found that CAC predicts subsequent CVD events better than does carotid IMT.
PMCID: PMC2555989  PMID: 18574091

Results 1-7 (7)