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.

Revised threshold values for neonatal oxygen saturation at mild and moderate altitudes.

AIM: The aim of this study was to determine reference values for oxygen saturation (SpO2 ) in neonates at mild and moderate altitudes. METHODS: Our study included 41 097 consecutively born, asymptomatic neonates from 35 hospitals, located in Yunnan, China, with altitudes ranging from 267 to 2202 m. Pre-and post-ductal SpO2 of each neonate was measured at 24 hours of age and before hospital discharge. All study participants, according to the altitude of birth, were categorised into three groups: low (0-500 m), mild (500-1500 m) and moderate altitude (1500-2500 m). RESULTS: Every 1000-m increase in altitude was associated with a 1.54 per cent decrease in mean SpO2 . The means of pre-ductal SpO2 at low, mild and moderate groups were 97.9%, 96.4% and 95.5%, respectively. We used the 2.5th percentile of SpO2 distribution as the cut-off for neonatal SpO2 screening and defined new cut-off values of ≤93% for mild altitudes, ≤92% for moderate altitudes and no adjustment for low altitudes. CONCLUSION: We recommend revised cut-off values for neonatal SpO2 at mild and moderate altitudes and provide new values for paediatricians to refer to when screening neonates for severe congenital heart or lung diseases.

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.

Genetic ancestry and the relationship of cigarette smoking to lung function and per cent emphysema in four race/ethnic groups: a cross-sectional study.

BACKGROUND: Cigarette smoking is the major cause of chronic obstructive pulmonary disease and emphysema. Recent studies suggest that susceptibility to cigarette smoke may vary by race/ethnicity; however, they were generally small and relied on self-reported race/ethnicity. OBJECTIVE: To test the hypothesis that relationships of smoking to lung function and per cent emphysema differ by genetic ancestry and self-reported race/ethnicity among Caucasians, African-Americans, Hispanics and Chinese-Americans. DESIGN: Cross-sectional population-based study of adults age 45-84 years in the USA. MEASUREMENTS: Principal components of genetic ancestry and continental ancestry estimated from one million genome-wide single nucleotide polymorphisms; pack-years of smoking; spirometry measured for 3344 participants; and per cent emphysema on computed tomography for 8224 participants. RESULTS: The prevalence of ever-smoking was: Caucasians, 57.6%; African-Americans, 56.4%; Hispanics, 46.7%; and Chinese-Americans, 26.8%. Every 10 pack-years was associated with -0.73% (95% CI -0.90% to -0.56%) decrement in the forced expiratory volume in 1 s to forced vital capacity (FEV1 to FVC) and a 0.23% (95% CI 0.08% to 0.38%) increase in per cent emphysema. There was no evidence that relationships of pack-years to the FEV1 to FVC, airflow obstruction and per cent emphysema varied by genetic ancestry (all p>0.10), self-reported race/ethnicity (all p>0.10) or, among African-Americans, African ancestry. There were small differences in relationships of pack-years to the FEV1 among male Chinese-Americans and to the FEV1 to FVC ratio with African and Native American ancestry among male Hispanics only. CONCLUSIONS: In this large cohort, there was little to no evidence that the associations of smoking to lung function and per cent emphysema differed by genetic ancestry or self-reported race/ethnicity.

Coronary calcium as a predictor of coronary events in four racial or ethnic groups.

BACKGROUND: In white populations, computed tomographic measurements of coronary-artery calcium predict coronary heart disease independently of traditional coronary risk factors. However, it is not known whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups. METHODS: We collected data on risk factors and performed scanning for coronary calcium in a population-based sample of 6722 men and women, of whom 38.6% were white, 27.6% were black, 21.9% were Hispanic, and 11.9% were Chinese. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 3.8 years. RESULTS: There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors. CONCLUSIONS: The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected.

Risk factor differences for aortic versus coronary calcified atherosclerosis: the multiethnic study of atherosclerosis.

OBJECTIVE: The goal of this study was to compare and contrast coronary artery calcium (CAC) with abdominal aortic calcium (AAC) in terms of their associations with traditional and novel cardiovascular disease (CVD) risk factors. METHODS AND RESULTS: We measured both AAC and CAC using computed tomography scans in 1974 men and women aged 45 to 84 years from a multiethnic cohort. Traditional and novel CVD risk factors were examined separately in relation to AAC and CAC, using logistic regression for qualitative categorical comparisons and multiple linear regression for quantitative continuous comparisons. AAC was significantly associated with cigarette smoking and dyslipidemia and showed no gender difference. In contrast, CAC showed much weaker associations with smoking and dyslipidemia and a strong male predominance. Age and hypertension were associated similarly and significantly with AAC and CAC. Novel risk factors generally showed no independent association with either calcium measure, although in subset analyses, phosphorus, but not calcium, was related to CAC. The receiver operating characteristic curves for the qualitative results and the r(2) values for the quantitative analyses were both much higher for AAC than for CAC. CONCLUSIONS: AAC showed stronger correlations with most CVD risk factors than did CAC. The predictive value of AAC compared with CAC for incident CVD events remains to be evaluated.

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.

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.

Incidence and predictors of hypertension among rural Chinese adults: results from Liaoning province.

UNLABELLED: OBJECTIVE We wanted to determine the incidence of hypertension and its risk factors among rural Chinese adults. METHODS: A population-based sample of 24,360 rural Chinese adults aged 35 years and older and free from hypertension at baseline was observed from 2004-2006 to 2008. Incident hypertension was defined as a systolic pressure of 140 mm Hg or greater, diastolic pressure of 90 mm Hg or greater, or current use of antihypertensive medication. RESULTS: During a mean follow-up period of 28 months, 29.6% of men and 23.4% of women developed hypertension. The age-adjusted incidence was higher in men (12.75 per 100 person-years) than in women (10.04 per 100 person-years). Among men, independent predictors of incident hypertension were baseline age (hazard ratio [HR] = 1.11; 95% confidence interval [CI], 1.10-1.13), Mongolian ethnicity (HR = 1.09; 95% CI, 1.01-1.18), use of alcohol, (HR = 1.14; 95% CI, 1.06-1.23), high income vs low income (HR = 1.11; 95% CI, 1.00-1.22; and HR = 1.11; 95% CI, 1.03-1.20), prehypertension vs normotension (HR = 1.18; 95% CI, 1.08-1.28), overweight and obesity (HR = 1.28; 95% CI, 1.17-1.40), baseline salt intake (HR = 1.00; 95% CI, 1.00-1.01) and family history of hypertension (HR = 1.14; 95% CI, 1.03-1.27). With the exception of use of alcohol and mean income, the results were similar for women, except that low physical activity was shown as a risk factors as well. The awareness, treatment, and control rates for newly developed hypertension were 29.9%, 19.5%, and 1.5%, respectively. CONCLUSIONS: These data indicate that the incidence of hypertension is high among these rural Chinese adults and that it is associated with many risk factors. Our findings further suggest that most newly developed hypertension cases are not treated. The increases in hypertension are probably related to rapid social changes in our country and may apply to other areas of the developing world. These findings call for urgent improvements in hypertension prevention and control programs in rural China.

High-dose B vitamin supplementation and progression of subclinical atherosclerosis: a randomized controlled trial.

BACKGROUND AND PURPOSE: Although plasma total homocysteine (tHcy) levels are associated with cardiovascular disease, it remains unclear whether homocysteine is a cause or a marker of atherosclerotic vascular disease. We determined whether reduction of tHcy levels with B vitamin supplementation reduces subclinical atherosclerosis progression. METHODS: In this double-blind clinical trial, 506 participants 40 to 89 years of age with an initial tHcy >8.5 micromol/L without diabetes and cardiovascular disease were randomized to high-dose B vitamin supplementation (5 mg folic acid+0.4 mg vitamin B(12)+50 mg vitamin B(6)) or matching placebo for 3.1 years. Subclinical atherosclerosis progression across 3 vascular beds was assessed using high-resolution B-mode ultrasonography to measure carotid artery intima media thickness (primary outcome) and multidetector spiral CT to measure aortic and coronary artery calcium (secondary outcome). RESULTS: Although the overall carotid artery intima media thickness progression rate was lower with B vitamin supplementation than with placebo, statistically significant between-group differences were not found (P=0.31). However, among subjects with baseline tHcy >or=9.1 micromol/L, those randomized to B vitamin supplementation had a statistically significant lower average rate of carotid artery intima media thickness progression compared with placebo (P=0.02); among subjects with a baseline tHcy <9.1 micromol/L, there was no significant treatment effect (probability value for treatment interaction=0.02). B vitamin supplementation had no effect on progression of aortic or coronary artery calcification overall or within subgroups. CONCLUSIONS: High-dose B vitamin supplementation significantly reduces progression of early-stage subclinical atherosclerosis (carotid artery intima media thickness) in well-nourished healthy B vitamin "replete" individuals at low risk for cardiovascular disease with a fasting tHcy >or=9.1 micromol/L.

Fine particulate matter air pollution, proximity to traffic, and aortic atherosclerosis.

BACKGROUND: The initiation and acceleration of atherosclerosis is hypothesized as a physiologic mechanism underlying associations between air pollution and cardiovascular effects. Despite toxicologic evidence, epidemiologic data are limited. METHODS: In this cross-sectional analysis we investigated exposure to fine particulate matter (PM2.5) and residential proximity to major roads in relation to abdominal aortic calcification, a sensitive indicator of systemic atherosclerosis. Aortic calcification was measured by computed tomography among 1147 persons, in 5 US metropolitan areas, enrolled in the Multi-Ethnic Study of Atherosclerosis. The presence and quantity of aortic calcification were modeled using relative risk regression and linear regression, respectively, with adjustment for potential confounders. RESULTS: We observed a slightly elevated risk of aortic calcification (RR = 1.06; 95% confidence interval = 0.96-1.16) with a 10 microg/m contrast in PM2.5. The PM2.5-associated risk of aortic calcification was stronger among participants with long-term residence near a PM2.5 monitor (RR = 1.11; 1.00-1.24) and among participants not recently employed outside the home (RR = 1.10; 1.00-1.22). PM2.5 was not associated with an increase in the quantity of aortic calcification (Agatston score) and no roadway proximity effects were noted. There was indication of PM2.5 effect modification by lipid-lowering medication use, with greater effects among users, and PM2.5 associations were observed most consistently among Hispanics. CONCLUSIONS: Although we did not find persuasive associations across our full study population, associations were stronger among participants with less exposure misclassification. These findings support the hypothesis of a relationship between particulate air pollution and systemic atherosclerosis.

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.

Subclinical atherosclerosis is weakly associated with lower cognitive function in healthy hyperhomocysteinemic adults without clinical cardiovascular disease.

OBJECTIVE: Atherosclerosis is the most common pathologic process underlying cardiovascular disease (CVD). It is not well known whether subclinical atherosclerosis is an independent risk factor for lower cognitive function among individuals without clinically evident CVD. METHODS: We examined cross-sectional associations between subclinical atherosclerosis and cognitive function in a community-based sample of otherwise healthy adults with plasma homocysteine >or=8.5 micromol/L enrolled in the BVAIT study (n = 504, mean age 61 years). Carotid artery intima-media thickness (CIMT), coronary artery calcium (CAC) and abdominal aortic calcium (AAC) were used to measure subclinical atherosclerosis. Cognitive function was assessed with a battery of neuropsychological tests. A principal components analysis was used to extract five uncorrelated cognitive factors from scores on individual tests, and a measure of global cognition was derived. Multivariable linear regression was used to examine the association between subclinical atherosclerosis and cognitive function, adjusting for other correlates of cognition. RESULTS: Increasing thickness of CIMT was associated with significantly lower scores on the verbal learning factor (beta = -0.07 per 0.1 mm increase CIMT [SE(beta) = 0.03], p = 0.01). CAC and AAC were not individually associated with any of the cognitive factors. CONCLUSIONS: This study provides evidence that increasing CIMT is weakly associated with lower verbal learning abilities but not global cognition in a population of otherwise healthy middle-to-older aged adults with elevated plasma homocysteine levels but without clinically evident CVD. The association between CIMT and poor verbal learning may pertain particularly to men.

Abnormal T-wave axis is associated with coronary artery calcification in older adults.

OBJECTIVE: To determine whether T-wave axis on the resting electrocardiogram (ECG) is associated with coronary artery calcification (CAC) score, a measurement of coronary atherosclerosis, in older adults. METHODS: The sample consisted of 2004 adults aged 66 and over participating in the prospective, population-based Age-Gene/Environment Susceptibility-Reykjavik Study. The cohort was divided into gender-stratified quartiles based upon Agatston CAC score derived from computerized tomography. Frontal T-axis deviation from 45 degrees was assessed using surface ECG. Statistical analysis was performed with Tobit regression models adjusted for demographic and cardiovascular risk factors. RESULTS: In the entire study population, T-axis deviation from 45 degrees was significantly associated with increasing CAC score in men (p<0.001) and women (p=0.03). In men without clinically recognized coronary heart disease (CHD), the association with CAC score remained statistically significant (p=0.02). This association was significant among women without CHD once male CAC cut points were used (p=0.05). CONCLUSION: An abnormal T-wave axis is associated with an increasing CAC score in this population of Icelandic older adults. This association remains in the subgroup of subjects without clinical CHD.

Pulse pressure correlates with coronary artery calcification and risk for coronary heart disease: a study of elderly individuals in the rural region of Southwest China.

AIM: This study aimed to define the relationship between pulse pressure (PP) and coronary artery calcification (CAC), a proven surrogate marker for coronary heart disease. PATIENTS AND METHODS: A total of 170 participants 50-70 years of age from 11 villages of Yunnan Province of China were enrolled randomly into this study. They were examined routinely for diastolic and systolic blood pressure, PP, and CAC. RESULTS: The average PP in the CAC-positive group was significantly higher than that in the CAC-negative group. In the positive CAC group, there were significantly positive correlations between PP and CAC score, volume, mass, as well as density. The area under the receiver operating characteristic curve analysis showed that PP performed well in predicting CAC. CONCLUSION: In conclusion, among the rural people of southwest of China, PP correlates positively with the coronary calcium Agatston score, volume, mass, and density. PP predicted CAC as well as Framingham Risk Score. The measurement of PP widening may serve as an alternative and convenient method for assessing CAC risk in rural populations with poor accessibility and economic disadvantage over coronary computed tomography scanning.

Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: The Multi-Ethnic Study of Atherosclerosis (MESA) provides an opportunity to study the association of traditional cardiovascular risk factors with the incidence and progression of coronary artery calcium (CAC) in a large community-based cohort with no evidence of clinical cardiovascular disease. METHODS AND RESULTS: Follow-up CAC measurements were available for 5756 participants with an average of 2.4 years between scans. The incidence of newly detectable CAC averaged 6.6% per year. Incidence increased steadily across age, ranging from <5% annually in those <50 years of age to >12% in those >80 years of age. Median annual change in CAC for those with existing calcification at baseline was 14 Agatston units for women and 21 Agatston units for men. Most traditional cardiovascular risk factors were associated with both the risk of developing new incident coronary calcium and increases in existing calcification. These included age, male gender, white race/ethnicity, hypertension, body mass index, diabetes mellitus, glucose, and family history of heart attack. Factors also existed that were related only to incident CAC risk, such as low- and high-density lipoprotein cholesterol and creatinine. Diabetes mellitus had the strongest association with CAC progression for blacks and the weakest for Hispanics, with intermediate associations for whites and Chinese. CONCLUSIONS: This is the first large multiethnic study reporting on the incidence and progression of CAC. Standard coronary risk factors were generally related to both CAC incidence and progression. Whites had more incident CAC and CAC progression than the other 3 racial/ethnic groups. Except for diabetes mellitus, risk factor relationships were similar across racial/ethnic groups.

Molecular, endocrine, and genetic mechanisms of arterial calcification.

Pathologists have recognized arterial calcification for over a century. Recent years have witnessed a strong resurgence of interest in atherosclerotic plaque calcification because it: 1) can be easily detected noninvasively; 2) closely correlates with the amount of atherosclerotic plaque; 3) serves as a surrogate measure for atherosclerosis, allowing preclinical detection of the disease; and 4) is associated with heightened risk of adverse cardiovascular events. There are two major types of calcification in arteries: calcification of the media tunica layer (sometimes called Mönckeberg's sclerosis), and calcification within subdomains of atherosclerotic plaque within the intimal layer of the artery. There are important similarities and differences between these two entities. Of particular interest are increasing parallels between cellular and molecular features of arterial calcification and bone biology, and this has led to accelerating interest in understanding how and why bone-like mineral deposits may form in arteries. Here, we review the two major pathological types of arterial calcification, the proposed models of calcification, and endocrine and genetic determinants that affect arterial calcification. In addition, we highlight areas requiring further investigation.

Coronary calcium coverage score: determination, correlates, and predictive accuracy in the Multi-Ethnic Study of Atherosclerosis.

PURPOSE: To develop a new calcium score for use with unenhanced cardiac computed tomography (CT) that can be used to define the percentage of coronary arteries affected by calcium and to correlate this score with risk factors and cardiovascular events. MATERIALS AND METHODS: Institutional review boards at all participating centers approved this HIPAA-compliant study, and all participants gave written informed consent. Calcium coverage score (CCS), which represents the percentage of coronary arteries affected by calcific plaque, was calculated for 3252 participants in the Multi-Ethnic Study of Atherosclerosis in whom calcific plaque was detected with CT. Quasi-Poisson models were used to estimate associations (assessed by using t tests with robust standard errors) between CCS and risk factors. Associations between the CCS, Agatston, and calcium mass scores (hereafter, mass scores) and outcomes were estimated and assessed by using Cox proportional hazards models with Wald tests. The predictive ability of these models was assessed by using area under the receiver operating characteristic curves and bootstrap t tests. RESULTS: After adjustments were made for age, race, ethnicity, and sex in the quasi-Poisson model, CCS was associated with hypertension, dyslipidemia, and diabetes (P < .001 for all diseases). After adjustments for age and sex, a twofold increase in CCS was associated with a 52% (95% confidence interval: 34%, 72%) increase in risk for any coronary heart disease (CHD) event. When Agatston or mass scores were included with CCS in a Cox model for prediction of CHD events, neither Agatston score nor mass score was a significant predictor, whereas CCS remained significantly associated with CHD events. Although receiver operating characteristic curves suggested that there was a difference between CCS score and Agatston and mass scores in prediction of a cardiac event, no differences in prediction of hard cardiac events (myocardial infarction, death) were found. CONCLUSION: Both spatial distribution and amount of calcified plaque contribute to risk for CHD.

Relationships of thoracic aortic wall calcification to cardiovascular risk factors: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: The aim of this article is to determine the relationships between aortic wall calcification (AWC) including ascending and descending thoracic aortic calcification and sex, race/ethnicity, age, and traditional risk factors. Allison et al (Arterioscler Thromb Vasc Biol. 2004;24:331-336) previously described the relationship of noted risk factors and AWC as detected by computed tomography (CT) in smaller cohorts. We performed a cross-sectional study to determine which of these variables are independently associated with thoracic calcium. METHODS: The MESA population included a population-based sample of 4 ethnic groups (12% Chinese, 38% white, 22% Hispanic, and 28% black) of 6814 women and men aged 45 to 84 years. Computed tomographic scans were performed for all participants. We quantified AWC, which ranged from the lower edge of the pulmonary artery bifurcation to the cardiac apex. Multivariable logistic regression was used to evaluate relationships between AWC and measured cardiovascular risk factors. RESULTS: Overall prevalence of AWC was 28.0%. In the ethnic groups, prevalence of AWC was 32.4% Chinese, 32.4% white, 24.9% Hispanic, and 22.4% black. All age categories of females had a higher prevalence of thoracic calcification than males (total age prevalence 29.1% and 26.8%, respectively). Aortic wall calcifications were most strongly associated with hypertension and current smoking. In addition, diabetes, hypercholesterolemia, high level of low-density lipoprotein, low level of high-density lipoprotein, family history of myocardial infarction , and high C-reactive protein were all associated with increased AWC. Overall P value for difference between sexes for prevalence of AWC is 0.037. Overall P value for difference between race for prevalence of AWC is <.001. The only significant sex differences distributed by race were for Chinese (P = .035) and Hispanic (P = .042) participants. CONCLUSIONS: Risk factors for aortic calcification were similar to cardiovascular risk factors in a large population-based cohort. Surprisingly, AWC was similar for the Chinese and white populations despite the fact that MESA demonstrated that coronary calcium was more prevalent in the white population. Further studies are needed to investigate whether aortic calcification is a risk factor for coronary disease, independent of coronary calcification.

Relation of Framingham risk score to subclinical atherosclerosis evaluated across three arterial sites.

The Framingham risk score (FRS) is widely used in clinical practice to identify subjects at high risk for developing coronary heart disease. However, FRS may not accurately identify subjects at risk. We measured subclinical atherosclerosis in the coronary arteries and aorta with the presence of calcium and in the common carotid artery by intima-media thickness in 498 healthy subjects. The distribution of these subclinical atherosclerosis measures was evaluated across 3 strata of the FRS. Coronary arteries with the presence of calcium, aorta with the presence of calcium, and carotid artery by intima-media thickness were significantly independently associated with FRS. The FRS increased with the number of arterial sites with atherosclerosis; 69% of the subjects categorized in the low risk group (FRS <10%), 95% of the intermediate risk group (FRS 10% to 20%), and 100% of the high risk group (FRS >20%) had > or = 1 vascular imaging studies demonstrating subclinical atherosclerosis. In the low risk group, subjects with atherosclerosis had a longer history of lifetime smoking compared with those without atherosclerosis. In conclusion, subclinical atherosclerosis is prominent across the spectrum of FRS. Evaluation of subclinical atherosclerosis in different arterial sites in addition to FRS may be useful in targeting subjects for lifestyle and other interventions.