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1.  Trends in control of cardiovascular risk factors among US adults with type 2 diabetes from 1999 to 2010: Comparison by prevalent cardiovascular disease status 
Most patients with type 2 diabetes mellitus (T2DM) suffer from cardiovascular disease (CVD). Whether CVD risk factors have improved in those with DM with and without CVD is not established. We compared risk factor levels and goal attainment in US adults with diabetes with and without CVD.
We examined 2403 adults (aged ≥ 18 years) in the United States with T2DM (n = 654, 27% with CVD) across 1999–2010 using the US National Health and Nutrition Examination Survey (NHANES) and evaluated control of hemoglobin A1c (HbA1c), blood pressure (BP), low-density lipoprotein cholesterol (LDL-C) and body mass index (BMI) in those with DM with versus without CVD.
The proportions controlled for HbA1c, BP and LDL-C have improved (p < 0.001) overall between 1999 and 2010, but only 24% were at goal for all three factors in 2009–2010. There were improvements in BP, triglycerides and LDL-C in those with CVD, and in those without CVD, there were also improvements in control of all parameters, although changes in mean levels of risk factors were less impressive.
Despite modest improvement over time, in most CVD risk factors, only one-fourth of those with T2DM are at goal for HbA1c, BP and LDL-C, with improvements seen in those without CVD more often than those with CVD.
PMCID: PMC4227398  PMID: 23975724
Diabetes; risk factors; cardiovascular disease; trends
2.  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
3.  Coronary Artery Calcium Screening in Persons with Metabolic Syndrome and Diabetes: Implications for Prevention 
Diabetes and metabolic syndrome are major risk factors for coronary heart disease (CHD). Many patients suffering CHD events are not adequately identified by traditional risk assessment, suggesting the need for early detection of subclinical CHD to identify those at highest risk. Coronary artery calcium (CAC) screening has added utility in categorizing patients with intermediate and high risk of CHD events, and a growing body of evidence suggests its use for CHD risk assessment in persons with metabolic syndrome and diabetes mellitus. These studies demonstrate the presence and extent of CAC to be greater in those with these conditions, compared to those without, and that CHD risk varies greatly according to the extent of CAC both in persons with and without metabolic syndrome and diabetes mellitus. More recently, guidelines regarding the use of CAC screening have been extended to those with diabetes mellitus, helping to further stratify those patients that may benefit from more intensive therapy. This review evaluates the role and possible benefits of CAC screening, with a focus on those with metabolic syndrome and diabetes mellitus for evaluating the risk for CHD.
PMCID: PMC3840472  PMID: 23438153
4.  Bone mineral density and atherosclerosis: The Multi-Ethnic Study of Atherosclerosis, Abdominal Aortic Calcium Study 
Atherosclerosis  2009;209(1):283-289.
Molecular and cell biology studies have demonstrated an association between bone and arterial wall disease, but the significance of a population-level association is less clear and potentially confounded by inability to account for shared risk factors.
To test population-level associations between atherosclerosis types and bone integrity.
Main Outcome Measures
Volumetric trabecular lumbar bone mineral density (vBMD), ankle-brachial index (ABI), intima-media thickness of the common carotid (CCA-IMT) and internal carotid (ICA-IMT) arteries, and carotid plaque echogenicity.
Design, Setting and Participants
A random subset of participants from the Multi-Ethnic Study of Atherosclerosis (MESA) assessed between 2002 and 2005.
904 post-menopausal female (62.4 years; 62% non-white; 12% ABI<1; 17% CCA-IMT>1mm; 33% ICA-IMT>1mm) and 929 male (61.4 years; 58% non-white; 6% ABI<1; 25% CCA-IMT>1mm; 40% ICA-IMT>1mm) were included. In serial, sex-specific regression models adjusting for age, ethnicity, body mass index, dyslipidemia, hypertension, smoking, alcohol consumption, diabetes, homocysteine, interleukin-6, sex hormones, and renal function, lower vBMD was associated with lower ABI in men (p for trend <0.01) and greater ICA-IMT in men (p for trend <0.02). CCA-IMT was not associated with vBMD in men or women. Carotid plaque echogenicity was independently associated with lower vBMD in both men (trend p=0.01) and women (trend p<0.04). In all models, adjustment did not materially affect results.
Lower vBMD is independently associated with structural and functional measures of atherosclerosis in men and with more advanced and calcified carotid atherosclerotic plaques in both sexes.
PMCID: PMC4254856  PMID: 19819456
5.  Impact of Inflammatory Biomarkers on Relation of High Density Lipoprotein-Cholesterol with Incident Coronary Heart Disease: Cardiovascular Health Study 
Atherosclerosis  2013;231(2):10.1016/j.atherosclerosis.2013.08.036.
Inflammatory factors and low HDL-C relate to CHD risk, but whether inflammation attenuates any protective association of high HDL-C is unknown.
Investigate inflammatory markers' individual and collective impact on the association of HDL-C with incident coronary heart disease (CHD).
In 3,888 older adults without known cardiovascular disease (CVD), we examined if the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and lipoprotein-associated phospholipase A2 (Lp-PLA2) modify the relation of HDL-C with CHD. HDL-C, CRP, IL-6, and Lp-PLA2 values were grouped as using gender-specific tertiles. Also, an inflammation index of z-score sums for CRP, IL-6, and Lp-PLA2 was categorized into tertiles. We calculated CHD incidence for each HDL-C/inflammation group and performed Cox regression, adjusted for standard CVD risk factors and triglycerides to examine the relationship of combined HDL-C-inflammation groups with incident events.
CHD incidence (per 1,000 person years) was higher for higher levels of CRP, IL-6, and the index, and lower for higher levels of HDL-C. Compared to high HDL-C/low-inflammation categories (referent), adjusted HRs for incident CHD were increased for those with high HDL-C and high CRP (HR=1.50, p<0.01) or highest IL-6 tertile (HR=1.40, p<0.05), but not with highest Lp-PLA2 tertile. Higher CHD incidence was similarly seen for those with intermediate or low HDL-C accompanied by high CRP, high IL-6, or a high inflammatory index.
The protective relation of high HDL-C for incident CHD appears to be attenuated by greater inflammation.
PMCID: PMC3858257  PMID: 24267235
High Density Lipoprotein; Inflammation; C-Reactive Protein; Coronary Heart Disease
6.  Metabolic Syndrome, Diabetes, and Incidence and Progression of Coronary Calcium: The Multiethnic Study of Atherosclerosis (MESA) 
Jacc. Cardiovascular Imaging  2012;5(4):358-366.
The purpose of the study was to examine and compare the incidence and progression of coronary artery calcium (CAC) among persons with metabolic syndrome (MetS) and diabetes mellitus (DM), compared to those with neither condition.
MetS and DM are associated with subclinical atherosclerosis as evidenced by coronary artery calcium (CAC).
The Multiethnic Study of Atherosclerosis included 6,814 African-American, Asian, Caucasian, and Hispanic adults aged 45–84 free of cardiovascular disease at baseline. 5,662 subjects (51% female, mean age 61.0 ± 10.3 years) received baseline and follow-up (mean 2.4 years) cardiac CT scans. We compared the incidence of CAC in 2,927 subjects without CAC at baseline and progression of CAC in 2,735 subjects with CAC at baseline in those with MetS without DM (25.2%), DM without MetS (3.5%), or both DM and MetS (9.0%), compared to neither MetS nor DM (58%). Progression of CAC was also examined in relation to coronary heart disease events over an additional 4.9 years.
Relative to those with neither MetS nor DM, adjusted relative risks (95% confidence intervals) for incident CAC were 1.7 (1.4–2.0), 1.9 (1.4–2.4), and 1.8 (1.4–2.2) (all p<0.01) and absolute differences in mean progression (volume score) were 7.8 (4.0–11.6; p<0.01), 11.6 (2.7–20.5; p<0.05), and 22.6 (17.2–27.9; p<0.01) for those with MetS without DM, DM without MetS, and both DM and MetS, respectively. Similar findings were seen in analysis using Agatston calcium score. In addition, progression predicted CHD events in those with MetS without DM (adjusted hazard ratio 4.1, 95% CI=2.0–8.5, p<0.01) and DM (4.9 [1.3–18.4], p<0.05) among those in highest tertile of CAC increase vs. no increase).
Individuals with MetS and DM have a greater incidence and absolute progression of CAC compared to individuals without these conditions, with progression also predicting CHD events in those with MetS and DM.
PMCID: PMC3327555  PMID: 22498324
atherosclerosis; diabetes; risk factors; calcification
7.  Impact of Subclinical Atherosclerosis on Cardiovascular Disease Events in Individuals With Metabolic Syndrome and Diabetes 
Diabetes Care  2011;34(10):2285-2290.
While metabolic syndrome (MetS) and diabetes confer greater cardiovascular disease (CVD) risk, recent evidence suggests that individuals with these conditions have a wide range of risk. We evaluated whether screening for coronary artery calcium (CAC) and carotid intimal-medial thickness (CIMT) can improve CVD risk stratification over traditional risk factors (RFs) in people with MetS and diabetes.
We assessed CAC and CIMT in 6,603 people aged 45–84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). Cox regression examined the association of CAC and CIMT with coronary heart disease (CHD) and CVD over 6.4 years in MetS and diabetes.
Of the subjects, 1,686 (25%) had MetS but no diabetes and 881 (13%) had diabetes. Annual CHD event rates were 1.0% among MetS and 1.5% for diabetes. Ethnicity and RF-adjusted hazard ratios for CHD for CAC 1–99 to ≥400 vs. 0 in subjects with neither MetS nor diabetes ranged from 2.6 to 9.5; in those with MetS, they ranged from 3.9 to 11.9; and in those with diabetes, they ranged from 2.9 to 6.2 (all P < 0.05 to P < 0.001). Findings were similar for CVD. CAC increased the C-statistic for events (P < 0.001) over RFs and CIMT in each group while CIMT added negligibly to prediction over RFs.
Individuals with MetS or diabetes have low risks for CHD when CAC or CIMT is not increased. Prediction of CHD and CVD events is improved by CAC more than by CIMT. Screening for CAC or CIMT can stratify risk in people with MetS and diabetes and support the latest recommendations regarding CAC screening in those with diabetes.
PMCID: PMC3177707  PMID: 21844289
8.  Abdominal Aortic Calcium, Coronary Artery Calcium, and Cardiovascular Morbidity and Mortality in the Multi-Ethnic Study of Atherosclerosis 
To evaluate the predictive value of abdominal aortic calcium (AAC) for incident cardiovascular disease (CVD) independent of coronary artery calcium (CAC).
Approach and Results
We evaluated the association of AAC with CVD in 1974 men and women aged 45 to 84 years randomly selected from the Multi-Ethnic Study of Atherosclerosis participants who had complete AAC and CAC data from computed tomographic scans. AAC and CAC were each divided into following 3 percentile categories: 0 to 50th, 51st to 75th, and 76th to 100th. During a mean of 5.5 years of follow-up, there were 50 hard coronary heart disease events, 83 hard CVD events, 30 fatal CVD events, and 105 total deaths. In multivariable-adjusted Cox models including both AAC and CAC, comparing the fourth quartile with the ≤50th percentile, AAC and CAC were each significantly and independently predictive of hard coronary heart disease and hard CVD, with hazard ratios ranging from 2.4 to 4.4. For CVD mortality, the hazard ratio was highly significant for the fourth quartile of AAC, 5.9 (P=0.01), whereas the association for the fourth quartile of CAC (hazard ratio, 2.1) was not significant. For total mortality, the fourth quartile hazard ratio for AAC was 2.7 (P=0.001), and for CAC, it was 1.9, P=0.04. Area under the receiver operating characteristic curve analyses showed improvement for both AAC and CAC separately, although improvement was greater with CAC for hard coronary heart disease and hard CVD, and greater with AAC for CVD mortality and total mortality. Sensitivity analyses defining AAC and CAC as continuous variables mirrored these results.
AAC and CAC predicted hard coronary heart disease and hard CVD events independent of one another. Only AAC was independently related to CVD mortality, and AAC showed a stronger association than CAC with total mortality.
PMCID: PMC4153597  PMID: 24812323
aortic diseases; calcium; cardiovascular diseases; diagnostic imaging; epidemiology
9.  Gender and ethnic differences in the prevalence of type 2 diabetes among Asian subgroups in California 
To investigate gender and ethnic type 2 diabetes (DM) prevalences among California Asian subgroups versus other ethnic groups and if risk factors explain these differences.
We identified the prevalence of DM and associated risk factors, stratified by gender, among Chinese, Filipino, South Asian, Japanese, Korean, Vietnamese, Mexican, Other Hispanic, African American, Caucasian, and Native American adults in a large survey conducted in 2009 (n=46,091, projected n= 26.6 mil).
The highest age-adjusted DM prevalence was seen in Native Americans (32.4%), Filipinos (15.8%), and Japanese (11.8%) among men and in Native Americans (16.0%) and African Americans (13.3%) among women. Caucasian and Mexican men had higher DM prevalences than women. Age and risk factor-adjusted logistic regression showed DM more likely (relative to Caucasians) among women in Koreans (OR=4.6, p<0.01), Native Americans (OR=3.0, p<0.01), and Other Hispanics (OR 2.9, p<0.01) and among men in Filipinos (OR=7.0, p<0.01), South Asians (OR=4.7, p<0.01), and Native Americans (OR=4.7, p<0.01). No specific risk factors accounted for the gender differences.
Ethnic and gender differences in DM prevalence persist, even after adjusting for lifestyle and other risk factors; prevalence is high among certain Asian American subgroups. Different diabetes prevention approaches may be needed across ethnic/gender groups.
PMCID: PMC3769447  PMID: 23743139
type 2 diabetes prevalence; risk factors; gender difference; ethnicity
10.  Thoracic Aortic Calcification and Coronary Heart Disease Events: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Atherosclerosis  2010;215(1):196-202.
The presence and extent of coronary artery calcium (CAC) is an independent predictor of coronary heart disease (CHD) morbidity and mortality. Few studies have evaluated interactions or independent incremental risk for coronary and thoracic aortic calcification (TAC). The independent predictive value of TAC for CHD events is not well-established.
This study used risk factor and computed tomography scan data from 6,807 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Using the same images for each participant, TAC and CAC were each computed using the Agatston method. The study subjects were free of incident CHD at entry into the study.
The mean age of the study population (n=6807) was 62±10 years (47% males). At baseline, the prevalence of TAC and CAC was 28 % (1,904/6,809) and 50% (3393/6809), respectively. Over 4.5±0.9 years, a total of 232 participants (3.41%) had CHD events, of which 132 (1.94%) had a hard event (myocardial infarction, resuscitated cardiac arrest, or CHD death). There was a significant interaction between gender and TAC for CHD events (p<0.05). Specifically, in women, the risk of all CHD event was nearly 3-fold greater among those with any TAC (hazard ratio: 3.04, 95% CI; 1.60–5.76). After further adjustment for increasing CAC score, this risk was attenuated but remained robust (HR: 2.15, 95% CI: 1.10–4.17). Conversely, there was no significant association between TAC and incident CHD in men. In women, the likelihood ratio chi square statistics indicate that the addition of TAC contributed significantly to predicting incident CHD event above that provided by traditional risk factors alone (chi square= 12.44, p=0.0004) as well as risk factors + CAC scores (chi square= 5.33, p=0.02) . On the other hand, addition of TAC only contributed in the prediction of hard CHD events to traditional risk factors (chi-square=4.33, p=0.04) in women, without contributing to the model containing both risk factors and CAC scores (chi square=1.55, p=0.21).
Our study indicates that TAC is a significant predictor of future coronary events only in women, independent of CAC. On studies obtained for either cardiac or lung applications, determination of TAC may provide modest supplementary prognostic information in women with no extra cost or radiation.
PMCID: PMC4110678  PMID: 21227418
atherosclerosis; cardiac CT; coronary calcium; multi-detector CT; prognosis; thoracic atherosclerosis
11.  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
12.  Prevalence of and Risk Factors for Subclinical Cardiovascular Disease in Selected US Hispanic Ethnic Groups 
American journal of epidemiology  2008;167(8):962-969.
In this study, the authors determined the prevalence and extent of cardiovascular disease (CVD) risk factors and subclinical CVD in four US Hispanic subgroups, as well as associations between the CVD risk factors and subclinical CVD in these groups. Participants were 1,437 Hispanic men and women enrolled in the Multi-Ethnic Study of Atherosclerosis in 2000–2002. Fifty-six percent were Mexican-American, 12% were Dominican-American, 14% were Puerto Rican-American, and 18% were Other Hispanic-American. All participants underwent clinical examinations for coronary artery calcium, thoracic aortic calcium, carotid intimal-medial thickness, ankle-brachial index, left ventricular mass, and left ventricular size. Mexican Americans had the highest levels of coronary artery calcium, thoracic aortic calcium, and carotid intimal-medial thickness, while Puerto Rican Americans had the highest prevalence of an ankle-brachial index less than 1.0 and levels of left ventricular mass. The magnitudes of the associations between coronary artery calcium and age, sex, and body mass index were similar across all Hispanic subgroups. However, there were differences in the magnitude and significance of the associations between coronary artery calcium and hypertension, hypercholesterolemia, and cigarette smoking among the different Hispanic subgroups. This finding was also present for the other subclinical CVD measures. These results suggest a differential relationship between risk factors and either prevalence or extent of subclinical disease by Hispanic subgroup.
PMCID: PMC4107279  PMID: 18283034
atherosclerosis; cardiovascular diseases; ethnic groups; Hispanic Americans; risk factors
13.  Association Between Coronary Artery Calcification Progression and Microalbuminuria 
JACC. Cardiovascular imaging  2010;3(6):595-604.
This study sought to evaluate the relationship between microalbuminuria (MA) and the development and progression of atherosclerosis, as assessed by incident and progression of coronary artery calcification (CAC).
MA is associated with an increased risk of cardiovascular disease, but the mechanism by which MA imparts this increased risk is not known.
The MESA (Multi-Ethnic Study of Atherosclerosis) study is a prospective cohort study of 6,814 self-identified White, African-American, Hispanic, or Chinese participants free of clinical cardiovascular disease at entry. Of the 6,775 individuals with available urine albumin data, we excluded 97 subjects with macroalbuminuria and 1,023 with missing follow-up CAC data. The final study population consists of 5,666 subjects.
At baseline, individuals with MA were more likely to have CAC >0 compared with those without MA (62% vs. 48%, p < 0.0001). During a mean follow-up of 2.4 ± 0.8 years, those with MA and no CAC at baseline were more likely to develop CAC (relative risk [RR]: 2.05, 95% confidence interval [CI]: 1.41 to 3.02, p < 0.0001) as compared with those without MA in demographic-adjusted analyses. After multivariant adjustment, the relationship was attenuated but remained statistically significant (RR: 1.76, 95% CI: 1.19 to 2.61, p = 0.005). Among those with CAC at baseline, those with versus those without MA had a 15 (95% CI: 8 to 22, p < 0.0001) volume units higher median increase in CAC in demographic-adjusted analyses. After multivariant adjustment, MA remained associated with incident CAC (RR: 1.76, 95% CI: 1.19 to 2.61, p = 0.005) and with progression of CAC (median increase in CAC volume score of 9 [95% CI: 2 to 16, p = 0.009]), relative to those without MA.
This large multiethnic, population-based study of asymptomatic individuals demonstrates an increased risk of incident CAC as well as greater CAC progression among those with MA. Further study is needed to determine the degree to which MA precedes and predicts progression of atherosclerosis and how this information can be used to reduce cardiovascular events.
PMCID: PMC4083743  PMID: 20541715
coronary artery calcium; microalbuminuria; risk prediction; coronary heart disease; Multi-Ethnic Study of Atherosclerosis
14.  The Association of Framingham and Reynolds Risk Scores with Incidence and Progression of Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis 
To compare the association of the Framingham Risk Score (FRS) and Reynolds Risk Score (RRS) with subclinical atherosclerosis, assessed by incidence and progression of coronary artery calcium (CAC).
The comparative effectiveness of competing risk algorithms for indentifying subclinical atherosclerosis is unknown.
The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of 6,814 participants free of baseline CVD. All participants underwent risk factor assessment, as well as baseline and follow-up CAC testing. We assessed the performance of the FRS and RRS to predict CAC incidence and progression using relative risk and robust linear regression.
The study population included 5,140 individuals (61±10 years, 47% males, mean follow-up: 3.1±1.3 years). Among 53% of subjects (n=2,729) with no baseline CAC, 18% (n=510) developed incident CAC. Both the FRS and RRS were significantly predictive of incident CAC [RR 1.40 (95% CI 1.29 – 1.52), and RR 1.41 (95% CI 1.30 – 1.54) per 5% increase in risk, respectively] and CAC progression [mean CAC score change 6.92 (95% CI 5.31 – 8.54) and 6.82 (95% CI 5.51 – 8.14) per 5% increase]. Discordance in risk category classification (< or > 10% 10-year CHD risk) occurred in 13.7%, with only the RRS consistently adding predictive value for incidence and progression of CAC. These subclinical atherosclerosis findings are supported by a CHD events analysis over 5.6±0.7 year follow-up.
Both the RRS and FRS predict onset and progression of subclinical atherosclerosis. However, the RRS may provide additional predictive information when discordance between the scoring systems exists.
PMCID: PMC4079464  PMID: 22051329
coronary artery calcium progression; subclinical atherosclerosis; risk prediction; Reynolds Risk Score; Framingham Risk Score
15.  Low-Risk Lifestyle, Coronary Calcium, Cardiovascular Events, and Mortality: Results From MESA 
American Journal of Epidemiology  2013;178(1):12-21.
Unhealthy lifestyle habits are a major contributor to coronary artery disease. The purpose of the present study was to investigate the associations of smoking, weight maintenance, physical activity, and diet with coronary calcium, cardiovascular events, and mortality. US participants who were 44–84 years of age (n = 6,229) were followed in the Multi-Ethnic Study of Atherosclerosis from 2000 to 2010. A lifestyle score ranging from 0 to 4 was created using diet, exercise, body mass index, and smoking status. Coronary calcium was measured at baseline and a mean of 3.1 (standard deviation, 1.3) years later to assess calcium progression. Participants who experienced coronary events or died were followed for a median of 7.6 (standard deviation, 1.5) years. Participants with lifestyle scores of 1, 2, 3, and 4 were found to have mean adjusted annual calcium progressions that were 3.5 (95% confidence interval (CI): 0.0, 7.0), 4.2 (95% CI: 0.6, 7.9), 6.8 (95% CI: 2.0, 11.5), and 11.1 (95% CI: 2.2, 20.1) points per year slower, respectively, relative to the reference group (P = 0.003). Unadjusted hazard ratios for death by lifestyle score were as follows: for a score of 1, the hazard ratio was 0.79 (95% CI: 0.61, 1.03); for a score of 2, the hazard ratio was 0.61 (95% CI: 0.46, 0.81); for a score of 3, the hazard ratio was 0.49 (95% CI: 0.32, 0.75); and for a score of 4, the hazard ratio was 0.19 (95% CI: 0.05, 0.75) (P < 0.001 by log-rank test). In conclusion, a combination of regular exercise, healthy diet, smoking avoidance, and weight maintenance was associated with lower coronary calcium incidence, slower calcium progression, and lower all-cause mortality over 7.6 years.
PMCID: PMC3698994  PMID: 23733562
coronary artery disease; CT and MRI; diet; epidemiology; exercise; primary prevention; risk factors; weight reduction
16.  Global Coronary Heart Disease Risk Assessment of Individuals With the Metabolic Syndrome in the U.S.  
Diabetes Care  2008;31(7):1405-1409.
OBJECTIVE—Although metabolic syndrome is related to an increased risk of coronary heart disease (CHD) events, individuals with metabolic syndrome encompass a wide range of CHD risk levels. This study describes the distribution of 10-year CHD risk among U.S. adults with metabolic syndrome.
RESEARCH DESIGN AND METHODS—Metabolic syndrome was defined by the modified National Cholesterol Education Program (NCEP)/Third Adult Treatment Panel (ATP III) definition among 4,293 U.S. adults aged 20–79 years in the National Health and Nutrition Examination Survey 2003–2004. Low-, moderate-, moderately high–, and high-risk statuses were defined as <6, 6 to <10, 10–20, and >20% probability of CHD in 10 years (based on NCEP/ATP III Framingham risk score algorithms), respectively; those with diabetes or preexisting cardiovascular disease were assigned to high-risk status.
RESULTS—The weighted prevalence of metabolic syndrome by NCEP criteria in our study was 29.0% overall (30.0% in men and 27.9% in women, P = 0.28): 38.5% (30.7% men and 46.9% women) were classified as low risk, 8.5% (7.9% men and 9.1% women) were classified as moderate risk, 15.8% (23.4% men and 7.6% women) were classified as moderately high risk, and 37.3% (38.0% men and 36.5% women) were classified as high risk. The proportion at high risk increased with age but was similar among Hispanics, non-Hispanic whites, and non-Hispanic blacks.
CONCLUSIONS—Although many subjects with metabolic syndrome have a low calculated risk for CHD, about half have a moderately high or high risk, reinforcing the need for global risk assessment in individuals with metabolic syndrome to appropriately target intensity of treatment for underlying CHD risk factors.
PMCID: PMC2453646  PMID: 18375418
17.  Comparison of demographic factors and cardiovascular risk factor control among U.S. adults with type 2 diabetes by insulin treatment classification 
Data on glucose and cardiovascular disease (CVD) risk factor control among persons with type 2 diabetes mellitus (DM) according to insulin treatment status are lacking. We examined DM control, risk factors, and comorbidities among U.S. persons according to insulin treatment status.
In the U.S. National Health and Nutrition Examination Surveys 2003–2006, we examined in 10,637 adults aged ≥30 with type 2 DM the extent of control of A1c, LDL-C, HDL-C, triglycerides, and blood pressure (BP) and composite goal attainment by insulin use status.
6.6% (n=889, projected to 14.3 million) had type 2 DM; of these, 22.9% were insulin users and 57.2% were treated only by other diabetes medications. Overall, 58.2% had an A1c<7% (53 mmol/mol) (insulin users 33.1%, non-insulin treated 66.1%, and 77.9% of those not on medication, p<0.0001). Overall, 44.2% were at a BP goal of <130/80 mmHg, 43.8% had an LDL-C<100 mg/dl (2.6 mmol/L), and 13.9% a BMI<25 kg/m2. Only 10.2% were simultaneously at A1c, LDL, and BP goals (5.4% of those on insulin).
U.S. adults with type 2 DM, especially those treated with insulin remain inadequately controlled for A1c and CVD risk factors and have a high prevalence of comorbidities.
PMCID: PMC3931306  PMID: 22502939
Diabetes mellitus; Epidemiology; Cardiovascular risk factors; Insulin; Control
18.  Racial/ethnic differences in control of cardiovascular risk factors among type 2 diabetes patients in an insured, ambulatory care population☆,☆☆,★,★★ 
This paper examines differences in cardiovascular disease risk factor control among racial/ethnic minorities (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Hispanic/Latino, Black/African Americans) with type 2 diabetes compared to Non-Hispanic Whites with type 2 diabetes in an insured, outpatient setting.
A three-year, cross-sectional sample of 15,826 patients with type 2 diabetes was studied between 2008 and 2010. Goal attainment rates for three cardiovascular disease risk factors (HbA1c, BP, LDL) were estimated. Logistic regression was used to determine the association between patient characteristics and control of risk factors.
Only one fifth (21.1%) of patients achieved simultaneous goal attainment (HbA1c, BP, LDL). After adjustment for patient characteristics and treatment, Black/African American women and men, and Filipino and Hispanic/Latino men were significantly less likely to simultaneously achieve all three goals, compared to Non-Hispanic Whites. Of the three goals, patients were more likely to achieve HbA1c goals (68.7%) than BP (45.7%) or LDL (58.5%) goals. Racial/ethnic differences were more apparent in risk factors that were under better control (i.e. HbA1c).
Cardiovascular risk factor control in type 2 diabetes is suboptimal, even in an insured population. Special attention may be required for specific racial/ethnic/gender groups.
PMCID: PMC3587775  PMID: 23062328
Race/ethnicity; Primary prevention; Cardiovascular diseases; Disparities; Type 2 diabetes
19.  Cardiovascular risk assessment: addition of CKD and race to the Framingham equation 
American heart journal  2012;164(6):925-931.e2.
The value of the Framingham equation in predicting cardiovascular risk in African Americans and patients with chronic kidney disease (CKD) is unclear. The purpose of the study was to evaluate whether the addition of CKD and race to the Framingham equation improves risk stratification in hypertensive patients.
Participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) were studied. Those randomized to doxazosin, age greater than 74 years, and those with a history of coronary heart disease (CHD) were excluded. Two risk stratification models were developed using Cox proportional hazards models in a two-thirds developmental sample. The first model included the traditional Framingham risk factors. The second model included the traditional risk factors plus CKD, defined by eGFR categories, and stratification by race (Black vs. Non-Black). The primary outcome was a composite of fatal CHD, nonfatal MI, coronary revascularization, and hospitalized angina.
There were a total of 19,811 eligible subjects. In the validation cohort, there was no difference in C-statistics between the Framingham equation and the ALLHAT model including CKD and race. This was consistent across subgroups by race and gender and among those with CKD. One exception was among Non-Black women where the C-statistic was higher for the Framingham equation (0.68 vs 0.65, P=0.02). Additionally, net reclassification improvement was not significant for any subgroup based on race and gender, ranging from −5.5% to 4.4%.
The addition of CKD status and stratification by race does not improve risk prediction in high-risk hypertensive patients.
PMCID: PMC3511773  PMID: 23194494
coronary disease; chronic renal insufficiency; African Americans; risk assessment; Framingham
20.  Reduction in Framingham Risk of Cardiovascular Disease in Obese Patients Undergoing Laparoscopic Adjustable Gastric Banding 
Advances in Therapy  2013;30(7):684-696.
Obesity is a major risk factor for cardiovascular disease (CVD), with weight loss offering improvement in CVD risk factors.
To examine whether weight loss in laparoscopic adjustable gastric band (LAGB)-treated obese patients is associated with meaningful reductions in estimated 10- and 30- year Framingham CVD risk 12–15 months post-LAGB.
Obese adult patients [body mass index (BMI) ≥30 kg/m2] treated with LAGB were identified in a large US healthcare database. Patients without CVD at baseline and with measures of BMI, systolic blood pressure, diabetes, and smoking status at baseline and follow-up were eligible. Non-LAGB patients were propensity score matched to LAGB patients on baseline BMI, age, and gender. Estimated 10- and 30-year risk of developing CVD using office-based data, including BMI, was calculated at baseline and 12–15 months follow-up.
Mean BMI in LAGB patients (n = 647, average age 45.66 years, 81.1% female) decreased from 42.7 to 33.4 kg/m2 (P < 0.0001), with 35.4% no longer obese; 10- and 30-year estimated CVD risk decreased from 10.8 to 7.6% (P < 0.0001) and 44.34 to 32.30% (P < 0.0001), respectively, 12–15 months post-LAGB. Improvements were significantly greater than in non-LAGB patients (N = 4,295) (P < 0.0001). In the subset with lipid data (n = 74), improvements in total (−20.6 mg/dL; P < 0.05) and high-density lipoprotein (+10.6 mg/dL, P < 0.0001) cholesterol 1 year post-LAGB were also observed.
Data from a US healthcare database show that individuals undergoing LAGB have significant weight loss and reductions in estimated 10- to 30-year CVD risk within 1 year post-LAGB.
PMCID: PMC3747322  PMID: 23897217
Cardiology; Cardiovascular disease; Framingham risk score; Laparoscopic adjustable gastric banding; Obesity; Weight loss
21.  Genetics of coronary artery calcification among African Americans, a meta-analysis 
BMC Medical Genetics  2013;14:75.
Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants.
We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with ~2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse-variance weighted meta-analysis on results for 5,823 AA from 8 studies. Heritability was calculated using family studies. The most significant SNPs among AAs were evaluated in European Ancestry (EA) CAC data; conversely, the significance of published SNPs for CAC/CHD in EA was queried within our AA meta-analysis.
Heritability of CAC was lower in AA (~30%) than previously reported for EA (~50%). No SNP reached genome wide significance (p < 5E-08). Of 67 SNPs with p < 1E-05 in AA there was no evidence of association in EA CAC data. Four SNPs in regions previously implicated in CAC/CHD (at 9p21 and PHACTR1) in EA reached nominal significance for CAC in AA, with concordant direction. Among AA, rs16905644 (p = 4.08E-05) had the strongest association in the 9p21 region.
While we observed substantial heritability for CAC in AA, we failed to identify loci for CAC at genome-wide significant levels despite having adequate power to detect alleles with moderate to large effects. Although suggestive signals in AA were apparent at 9p21 and additional CAC and CAD EA loci, overall the data suggest that even larger samples and an ethnic specific focus will be required for GWAS discoveries for CAC in AA populations.
PMCID: PMC3733595  PMID: 23870195
Atherosclerosis; Coronary artery calcium; Genetics; Meta-analysis; African-American
22.  Effect of age on aortic atherosclerosis 
To examine the association of atherosclerosis burden in the survivors of an asymptomatic elderly cohort study and its relationship to other coronary risk factors (specifically, age) by evaluating aortic atherosclerotic wall burden by magnetic resonance imaging (MRI).
A total of 312 participants in an ongoing observational cohort study underwent cardiac and descending thoracic aorta imaging by MRI. Maximum wall thickness was measured and the mean wall thickness calculated. Wall/outer wall ratio was used as a normalized wall index (NWI) adjusted for artery size difference among participants. Percent wall volume (PWV) was calculated as NWI × 100.
In this asymptomatic cohort (mean age: 76 years), the mean (SD) aortic wall area and wall thickness were 222 ± 45 mm2 and 2.7 ± 0.4 mm, respectively. Maximum wall thickness was 3.4 ± 0.6 mm, and PWV was 32% ± 4%. Women appeared to have smaller wall area, but after correcting for their smaller artery size, had significantly higher PWV than men (P = 0.03). Older age was associated with larger wall area (P = 0.04 for trend) with similar PWVs. However, there were no statistically significant associations between standard risk factors, Framingham global risk, or metabolic syndrome status, therapy for cholesterol or hypertension, coronary or aortic calcium score, and the aortic wall burden. Aortic calcification was associated with coronary calcification.
Asymptomatic elderly in this cohort had a greater descending thoracic aortic wall volume that correlated with age, and women had a significantly increased PWV compared to men. In these survivors, the atherosclerotic aortic wall burden was not significantly associated with traditional risk factors or with coronary or aortic calcium scores or coronary calcium progression. Results suggest that age, or as yet unidentified risk factor(s), may be responsible for the increase in atherosclerosis.
PMCID: PMC3708052  PMID: 23888172
Aging; Aortic atherosclerosis; Magnetic resonance imaging; Atherosclerotic risk factors
24.  Long-Term Effects of Incident Diabetes Mellitus on Cardiovascular Outcomes in People Treated for Hypertension 
Thiazide-type diuretics are associated with an increased incidence of diabetes as compared to other anti-hypertension medications. In this study we determined long-term cardiovascular disease (CVD) consequences of incident diuretic-associated diabetes compared to the effects of incident diabetes associated with calcium channel and ACE inhibitor use.
Methods and Results
22,418 participants from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial with baseline diabetes, incident diabetes (7.5% with chlorthalidone, 5.6% with amlodipine, and 4.3% with lisinopril), or no diabetes at 2 years of in-trial follow-up were followed for a mean total of 6.9 years (2.9 years in-trial and 4 additional years post-trial through the use of national data bases). The primary outcome was CVD mortality (death due to coronary heart disease [CHD], stroke, heart failure, or other CVD). Among other outcomes were all-cause mortality, non-CVD mortality, and CHD (nonfatal myocardial infarction/fatal CHD). Participants on chlorthalidone with incident diabetes versus no diabetes had consistently lower, non-significant risk for CVD mortality (hazard ratio [HR] 1.04, 95% confidence interval (CI 0.74–1.47), all-cause mortality (HR 1.04, 95% CI 0.82–1.30), and non-CVD mortality (HR 1.05, 95% CI 0.77–1.42) than participants with incident diabetes on amlodipine or lisinopril (HR’s 1.22–1.53). Participants with incident diabetes had elevated CHD risk compared to those with no diabetes (HR 1.46, 95% CI 1.09–1.96) but those on chlorthalidone had significantly lower risk than those on lisinopril (HR 1.18 versus 2.57, p for interaction = 0.04).
Our findings suggest that thiazide-related incident diabetes has less adverse long-term CVD impact than incident diabetes that develops on other antihypertensive medications.
PMCID: PMC3359874  PMID: 22396585
diabetes mellitus; diuretics; cardiovascular diseases; mortality; ALLHAT
25.  Threshold for the Upper Normal Limit of Indexed Epicardial Fat Volume: Derivation in a Healthy Population and Validation in an Outcome-Based Study 
The American journal of cardiology  2011;108(11):1680-1685.
Epicardial fat volume (EFV) quantified on non-contrast cardiac CT (NCT) relates to cardiovascular prognosis. We sought to define the upper normal limit of body surface area (BSA)-indexed EFV in a healthy population and to validate it as a predictor of major adverse cardiovascular events (MACE). We analyzed NCT scans of 226 healthy, low Framingham risk score (≤6%, FRS) people performed for coronary calcium scoring (CCS). EFV was quantified using validated software and indexed (EFVi) to BSA. We defined the 95th-percentile as the upper normal limit. Subsequently, we re-analyzed a separate cohort of 232 participants from a previously published case-control study with 4-year follow-up and 58 cases of MACE to test the additive value of abnormally high EFVi for predicting MACE. Of the 226 healthy participants, 51% were men (mean age 52±9 years). EFV correlated to BSA (r=0.373, p<0.0001). Median, range, and 25th and 75th-percentiles of the non-normally distributed EFVi were 33.3, 10.8–96.6, and 24.5 and 45.5cm3/m2. The 95th-percentile definition of the upper normal limit of EFVi was 68.1cm3/m2. Regarding prediction of MACE, EFVi values higher than the newly-defined threshold emerged as a significant and independent predictor after controlling for confounders (OR 2.8, 95% CI 1.3–6.4, p=0.012), and trended in its additive value to the combination of CCS ≥400 and FRS (ROC-AUC 0.714 vs. 0.675, p=0.1277). In conclusion, in a healthy population, we determined 68.1cm3/m2 as the 95th-percentile threshold for abnormally high EFVi. EFVi exceeding this value independently predicted MACE and trended to add to CCS and FRS in this prediction.
PMCID: PMC3215795  PMID: 21880291
epicardial fat volume; body surface area; normal limits; threshold

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