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1.  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.
Context
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.
Objective
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.
Results
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.
Conclusions
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.
doi:10.1001/archinte.168.12.1333
PMCID: PMC2555989  PMID: 18574091
2.  Low free testosterone in HIV-infected men is not associated with subclinical cardiovascular disease 
HIV medicine  2012;13(6):358-366.
Objectives
Low testosterone (T) is associated with cardiovascular disease (CVD) and increased mortality in the general population; however, the impact of T on subclinical CVD in HIV disease is unknown. This study examined the relationships among free testosterone (FT), subclinical CVD, and HIV disease.
Methods
This was a cross-sectional analysis in 322 HIV-uninfected and 534 HIV-infected men in the Multicenter AIDS Cohort Study. Main outcomes were coronary artery calcification presence, defined as a coronary artery calcium (CAC) score > 10 (CAC score was the geometric mean of the Agatston scores of two computed tomography replicates), and far wall common carotid intima-media thickness (IMT)/carotid lesion presence by B-mode ultrasound.
Results
Compared with the HIV-uninfected men in our sample, HIV-infected men were younger, with lower body mass index (BMI) and more often Black. HIV-infected men had lower FT (age-adjusted FT 88.7 ng/dL vs. 101.7 ng/dL in HIV-uninfected men; P = 0.0004); however, FT was not associated with CAC, log carotid IMT, or the presence of carotid lesions. HIV status was not associated with CAC presence or log carotid IMT, but was associated with carotid lesion presence (adjusted odds ratio 1.69; 95% confidence interval 1.06, 2.71) in HIV-infected men compared with HIV-uninfected men.
Conclusions
Compared with HIV-uninfected men, HIV-infected men had lower FT, as well as more prevalent carotid lesions. In both groups, FT was not associated with CAC presence, log carotid IMT, or carotid lesion presence, suggesting that FT does not influence subclinical CVD in this population of men with and at risk for HIV infection.
doi:10.1111/j.1468-1293.2011.00988.x
PMCID: PMC3505881  PMID: 22296297
cardiovascular disease; HIV; testosterone
3.  Carotenoids as Protection Against Disability in Older Persons 
Rejuvenation research  2008;11(3):557-563.
The purpose was to examine the relationship of total plasma carotenoids, an indicator of fruit and vegetable intake, with walking speed and severe walking disability in older adults. Nine hundred twenty-eight men and women aged 65 to 102 years from the Invecchiare in Chianti (Aging in the Chianti Area [InCHIANTI]) study, a population-based cohort in Tuscany, Italy, were studied. Plasma carotenoids were measured at enrollment (1998–2000), and walking speed over 4 meters and 400 meters distance were assessed at enrollment and 6 years later (2004–2006). At enrollment, 85 of 928 (9.2%) participants had severe walking disability (defined as being unable to walk or having a walking speed at the 4-meter walking test < 0.4 m/sec). After adjusting for potential confounders, participants with high total plasma carotenoids were significantly less likely to have prevalent severe walking disability (odds ration [OR] 0.59, 95% confidence interval [CI] 0.38–0.90, p = 0.01) and had higher walking speed over 4 meters (β = 0.024, standard error [SE] = 0.011, p = 0.03) and over 400 meters (β = 0.019, SE = 0.010, p = 0.04). Of 621 participants without severe walking disability at enrollment who were seen 6 years later, 68 (11.0%) developed severe walking disability. After adjusting for potential confounders, higher total plasma carotenoids were associated with a significantly lower risk of developing severe walking disability (OR 0.51, 95% CI 0.30–0.86, p = 0.01) and were associated with a less steep decline in 4-meter walking speed over a 6-year follow-up (n = 579; β = 0.026, SE = 0.012, p = 0.03) and with lower incidence rates of being unable to successfully complete the 400-meter walking test at the 6-year follow-up visit (β = −0.054, SE = 0.03, p = 0.04). High plasma carotenoids concentrations may be protective against the decline in walking speed and the development of severe walking disability in older adults.
doi:10.1089/rej.2007.0581
PMCID: PMC2734103  PMID: 18593275
4.  Carotenoids as Protection Against Disability in Older Persons 
Rejuvenation Research  2008;11(3):557-563.
Abstract
The purpose was to examine the relationship of total plasma carotenoids, an indicator of fruit and vegetable intake, with walking speed and severe walking disability in older adults. Nine hundred twenty-eight men and women aged 65 to 102 years from the Invecchiare in Chianti (Aging in the Chianti Area [InCHIANTI]) study, a population-based cohort in Tuscany, Italy, were studied. Plasma carotenoids were measured at enrollment (1998–2000), and walking speed over 4 meters and 400 meters distance were assessed at enrollment and 6 years later (2004–2006). At enrollment, 85 of 928 (9.2%) participants had severe walking disability (defined as being unable to walk or having a walking speed at the 4-meter walking test < 0.4 m/sec). After adjusting for potential confounders, participants with high total plasma carotenoids were significantly less likely to have prevalent severe walking disability (odds ration [OR] 0.59, 95% confidence interval [CI] 0.38–0.90, p = 0.01) and had higher walking speed over 4 meters (β = 0.024, standard error [SE] = 0.011, p = 0.03) and over 400 meters (β = 0.019, SE = 0.010, p = 0.04). Of 621 participants without severe walking disability at enrollment who were seen 6 years later, 68 (11.0%) developed severe walking disability. After adjusting for potential confounders, higher total plasma carotenoids were associated with a significantly lower risk of developing severe walking disability (OR 0.51, 95% CI 0.30–0.86, p = 0.01) and were associated with a less steep decline in 4-meter walking speed over a 6-year follow-up (n = 579; β = 0.026, SE = 0.012, p = 0.03) and with lower incidence rates of being unable to successfully complete the 400-meter walking test at the 6-year follow-up visit (β = − 0.054, SE = 0.03, p = 0.04). High plasma carotenoids concentrations may be protective against the decline in walking speed and the development of severe walking disability in older adults.
doi:10.1089/rej.2007.0581
PMCID: PMC2734103  PMID: 18593275
5.  The relationship between walking speed and changes in cardiovascular risk factors during a 12-day walking tour to Santiago de Compostela: a cohort study 
BMJ Open  2012;2(3):e000875.
Objectives
Physical exercise has beneficial effects on cardiovascular risk factors. Knowledge about the effect of exercise intensity, specifically walking speed, on cardiovascular risk factors is limited. We report the relationship between walking speed and changes in cardiovascular risk factors in participants of a 12-day walking tour to Santiago de Compostela.
Design
Prospective cohort study.
Setting
Single-centre study with healthy middle-aged volunteers.
Participants
Healthy middle-aged men (n=15) and women (n=14). Subjects using lipid-lowering medication were excluded.
Intervention
Participants walked 281±10 km of the classical route to Santiago de Compostela in 12 days in 2009.
Primary and secondary outcome measures
Walking speed was recorded and blood pressure, weight, waist circumference, lipids and glucose were measured every other day. Changes in risk factors were compared between gender-pooled groups with faster and slower walking speed. Second, the relationship between walking speed and changes in risk factors was quantified using a linear mixed effects model.
Results
In the faster walking speed (4.6±0.2 km/h) group, high-density lipoprotein cholesterol (HDL-c) increased more than in the slower walking speed (4.1±0.2 km/h) group (difference in change between groups: 0.20; 95% CI −0.02 to 0.42 mmol/l), while low-density lipoprotein cholesterol (LDL-c) and total cholesterol decreased more in the slower walking speed group (differences in changes between groups: LDL-c: −0.50; 95% CI −0.88 to −0.12 mmol/l and total cholesterol: −0.75; 95% CI −1.19 to −0.31 mmol/l). A 1 km/h higher walking speed was related to an increase in HDL-c (0.24; 95% CI 0.12 to 0.30 mmol/l), LDL-c (0.18; 95% CI −0.16 to 0.42 mmol/l) and total cholesterol (0.36; 95% CI 0.12 to 0.60 mmol/l), adjusted for age, gender, smoking, body mass index and heart rate, during the whole walking tour.
Conclusions
Walking the same distance faster improves HDL-c more, while LDL-c and total cholesterol decrease more with lower walking speed independent of changes in body weight in healthy middle-aged subjects.
Article summary
Article focus
Physical exercise has beneficial effects on cardiovascular risk factors; however, the knowledge about the effect of exercise intensity, specifically walking speed, on cardiovascular risk factors is limited.
We report the relationship between walking speed and changes in cardiovascular risk factors in participants of a 12-day walking tour to Santiago de Compostela.
Key messages
In subjects walking a 12-day walking tour to Santiago de Compostela, with long daily stages:walking the same distance with higher walking speed was related to a higher increase in HDL-c, while walking with lower walking speed was related to larger decreases in LDL-c and total cholesterol, adjusted for age, gender, smoking, body mass index and heart rate.there was no relationship between walking speed and changes in weight, waist circumference, blood pressure, triglycerides or glucose.
Strengths and limitations of this study
All subjects walked the same overall distance, walking speed was measured and measurements of cardiovascular risk factors were conducted every other day.
This is a small study with 29 participants walking 281 km in 12 days. Whether the results of this study can be extrapolated to less exercise, and other types of exercise is not known.
doi:10.1136/bmjopen-2012-000875
PMCID: PMC3353125  PMID: 22581795
6.  Neuromuscular determinants of maximum walking speed in well-functioning older adults 
Experimental gerontology  2013;48(3):358-363.
Maximum walking speed may offer an advantage over usual walking speed for clinical assessment of age-related declines in mobility function that are due to neuromuscular impairment. The objective of this study was to determine the extent to which maximum walking speed is affected by neuromuscular function of the lower extremities in older adults. We recruited two groups of healthy, well functioning older adults who differed primarily on maximum walking speed. We hypothesized that individuals with slower maximum walking speed would exhibit reduced lower extremity muscle size and impaired plantarflexion force production and neuromuscular activation during a rapid contraction of the triceps surae muscle group (soleus (SO) and gastrocnemius (MG)).
All participants were required to have usual 10-meter walking speed >1.0 m/s. If the difference between usual and maximum 10m walking speed was < 0.6 m/s, the individual was assigned to the “Slower” group (n=8). If the difference between usual and maximum 10-meter walking speed was > 0.6 m/s, the individual was assigned to the “Faster” group (n=12). Peak rate of force development (RFD) and rate of neuromuscular activation (rate of EMG rise) of the triceps surae muscle group were assessed during a rapid plantarflexion movement. Muscle cross sectional area of the right triceps surae, quadriceps and hamstrings muscle groups was determined by magnetic resonance imaging.
Across participants, the difference between usual and maximal walking speed was predominantly dictated by maximum walking speed (r=.85). We therefore report maximum walking speed (1.76 and 2.17 m/s in Slower and Faster, p<.001) rather than the difference between usual and maximal. Plantarflexion RFD was 38% lower (p=.002) in Slower compared to Faster. MG rate of EMG rise was 34% lower (p=.01) in Slower than Faster, but SO rate of EMG rise did not differ between groups (p=.73). Contrary to our hypothesis, muscle CSA was not lower in Slower than Faster for the muscle groups tested, which included triceps surae (p=.44), quadriceps (p=.76) and hamstrings (p=.98). MG rate of EMG rise was positively associated with RFD and maximum 10m walking speed, but not usual 10m walking speed.
These findings support the conclusion that maximum walking speed is limited by impaired neuromuscular force and activation of the triceps surae muscle group. Future research should further evaluate the utility of maximum walking speed for use in clinical assessment to detect and monitor age-related functional decline.
doi:10.1016/j.exger.2013.01.010
PMCID: PMC3594593  PMID: 23376102
aging; walking; mobility; muscle; electromyography
7.  Subclinical Atherosclerotic Calcification and Cognitive Functioning in Middle-Aged Adults: The CARDIA Study 
Atherosclerosis  2013;231(1):10.1016/j.atherosclerosis.2013.08.038.
Objective
Cardiovascular risk factors in middle-age are associated with cognitive impairment and dementia in older age. Less is known about the burden of calcified subclinical atherosclerosis and cognition, especially in midlife. We examined the association of coronary artery and abdominal aortic calcified plaque (CAC and AAC, respectively) with cognitive functioning in middle-aged adults.
Methods
This cross-sectional study included 2,510 black and white adults (age: 43–55 years) without heart disease or stroke who completed a year 25 follow-up exam (2010–11) as part of the Coronary Artery Risk Development in Young Adults Study. CAC and AAC were measured with non-contrast computed tomography. Cognition was assessed with the Digit Symbol Substitution Test (DSST) (psychomotor speed), Stroop Test (executive function), and Rey Auditory Verbal Learning Test (RAVLT) (verbal memory).
Results
A greater amount of CAC and AAC was associated with worse performance on each test of cognitive function after adjustment for age, sex, race, education, and study center. Associations were attenuated, but remained significant for the DSST and RAVLT following additional adjustment for vascular risk factors, including adiposity, smoking, alcohol use, dyslipidemia, hypertension, and diabetes. Compared to participants without CAC or AAC, those with both CAC and AAC, but not CAC or AAC alone was associated with lower DSST scores (p<0.05).
Conclusions
In this community-based sample, greater subclinical atherosclerotic calcification was associated with worse psychomotor speed and memory in midlife. These findings underscore the importance of a life course approach to the study of cognitive impairment with aging.
doi:10.1016/j.atherosclerosis.2013.08.038
PMCID: PMC3828555  PMID: 24125414
atherosclerosis; heart disease; calcium score; cognition; subclinical disease; risk factors
8.  The Associations of Fetuin-A with Subclinical Cardiovascular Disease in Community-Dwelling Persons: the Rancho Bernardo Study 
Objective
To determine the association of fetuin-A with subclinical CVD in community-living individuals.
Background
Fetuin-A is a hepatic secretory protein that inhibits arterial calcium deposition in vitro. Lower fetuin-A levels are associated with arterial calcification and death in end-stage renal disease populations. The association of fetuin-A with subclinical cardiovascular disease (CVD) in the general population is unknown.
Methods
Among 1,375 community-living individuals without prevalent clinical CVD, we measured plasma fetuin-A concentrations measured by ELISA. Peripheral arterial disease (PAD) was defined by ankle brachial index (ABI) < 0.90, coronary artery calcification (CAC) was measured by computed tomography, and common and internal intima media thickness (cIMT) were measured by carotid ultrasound. PAD was measured concurrent with fetuin-A, and CAC and cIMT was measured 4.6 years (mean) later.
Results
Mean age was 70 ± 11 years and 64% were female. Fetuin-A levels were inversely associated with CAC severity. When evaluated as CAC categories (0, 1–100, 101–300, > 300) using ordinal logistic regression, each standard deviation higher fetuin-A was associated with a 31% lower odds of CAC severity (proportional odds ratio [POR] 0.69; 95% confidence interval [CI] 0.46, 0.92; p=0.008) in models adjusted for demographics, lifestyle factors, traditional CVD risk factors and kidney function. In contrast, no association of fetuin-A was observed with PAD or high common or internal cIMT in adjusted models.
Conclusions
Lower fetuin-A levels are independently associated with greater CAC severity, but not PAD or cIMT. If confirmed, fetuin-A may mark calcium deposition within the vasculature, but not atherosclerosis per se.
doi:10.1016/j.jacc.2011.08.035
PMCID: PMC3224791  PMID: 22115642
Fetuin-A; Cardiovascular Disease; Coronary Artery Calcification
9.  Association Between Duration of Overall and Abdominal Obesity Beginning in Young Adulthood and Coronary Artery Calcification in Middle Age 
JAMA  2013;310(3):280-288.
IMPORTANCE
Younger individuals are experiencing a greater cumulative exposure to excess adiposity over their lifetime. However, few studies have determined the consequences of long-term obesity.
OBJECTIVE
To examine whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of coronary artery calcification (CAC), a subclinical predictor of coronary heart disease.
DESIGN, SETTING, AND PARTICIPANTS
Prospective study of 3275 white and black adults aged 18 to 30 years at baseline in 1985–1986 who did not initially have overall obesity (body mass index [BMI] ≥30) or abdominal obesity (men: waist circumference [WC] >102 cm; women: >88 cm) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after baseline.
MAIN OUTCOMES AND MEASURES
Presence of CAC was measured by computed tomography at the year 15 (2000–2001), year 20 (2005–2006), or year 25 (2010–2011) follow-up examinations. Ten-year progression of CAC (2000–2001 to 2010–2011) was defined as incident CAC in 2010–2011 or an increase in CAC score of 20 Agatston units or greater.
RESULTS
During follow-up, 40.4% and 41.0% developed overall and abdominal obesity, respectively. Rates of CAC per 1000 person-years were higher for those who experienced more than 20 years vs 0 years of overall obesity (16.0 vs 11.0, respectively) and abdominal obesity (16.7 vs 11.0). Approximately 25.2% and 27.7% of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC vs 20.2% and 19.5% of those with 0 years. After adjustment for BMI or WC and potential confounders, the hazard ratios for CAC for each additional year of overall or abdominal obesity were 1.02 (95% CI, 1.01–1.03) and 1.03 (95% CI, 1.02–1.05), respectively. The adjusted odds ratios for CAC progression were 1.04 (95% CI, 1.01–1.06) and 1.04 (95% CI, 1.01–1.07), respectively. Associations were attenuated but largely persisted following additional adjustment for potential intermediate metabolic factors during follow-up.
CONCLUSIONS AND RELEVANCE
Longer duration of overall and abdominal obesity was associated with subclinical coronary heart disease and its progression through midlife independent of the degree of adiposity. Preventing or at least delaying the onset of obesity in young adulthood may lower the risk of developing atherosclerosis through middle age.
doi:10.1001/jama.2013.7833
PMCID: PMC4226407  PMID: 23860986
10.  Fatty Liver, Insulin Resistance, and Features of Metabolic Syndrome 
Diabetes Care  2012;35(11):2359-2364.
OBJECTIVE
Nonalcoholic fatty liver disease (NAFLD) coexists with insulin resistance (IR), but it is uncertain whether NAFLD and IR contribute independently to atherosclerosis. We tested whether fatty liver, IR, and metabolic syndrome (MetS) features (waist, glucose, triglyceride, HDL cholesterol [HDL-C], and blood pressure) were associated with a marker of atherosclerosis (coronary artery calcium [CAC] score >0), independently of cardiovascular risk factors and cardiovascular disease (CVD).
RESEARCH DESIGN AND METHODS
Data were analyzed from a South Korean occupational cohort of 10,153 people who all received ultrasound measurements of fatty liver and a cardiac computed tomography CAC score. IR was defined by homeostasis model assessment of IR (HOMA-IR) ≥75th percentile. Odds ratios (ORs) (95% CIs) for the presence of a CAC score >0 were estimated using logistic regression.
RESULTS
There were 915 people with a CAC score >0. MetS features were increased (glucose, blood pressure, triglyceride, and waist) or decreased (HDL-C) among people with a CAC score >0 (all comparisons against CAC score ≤0; P < 0.0001). Of subjects with a CAC score >0, 55% had fatty liver and 33.7% were insulin resistant. Fatty liver (OR 1.21 [95% CI 1.01–1.45]; P = 0.04) and HOMA-IR (1.10 [1.02–1.18]; P = 0.02) were associated with CAC score >0, independently of all MetS features, conventional cardiovascular risk factors, and prior evidence of CVD. The presence of IR and fatty liver combined was associated with CAC score >0 (1.53 [1.20–1.95]; P = 0.001).
CONCLUSIONS
Fatty liver and HOMA-IR are both associated with a CAC score >0 (independently of each other), features of MetS, conventional cardiovascular risk factors, and existing CVD.
doi:10.2337/dc12-0515
PMCID: PMC3476919  PMID: 22829522
11.  The Association of Framingham and Reynolds Risk Scores with Incidence and Progression of Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis 
Objectives
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).
Background
The comparative effectiveness of competing risk algorithms for indentifying subclinical atherosclerosis is unknown.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1016/j.jacc.2011.08.022
PMCID: PMC4079464  PMID: 22051329
coronary artery calcium progression; subclinical atherosclerosis; risk prediction; Reynolds Risk Score; Framingham Risk Score
12.  Vitamin D Levels and Markers of Arterial Dysfunction in HIV 
Abstract
HIV-infected patients have low vitamin D levels as well as an increase in cardiovascular (CVD) risk. We examined the relationship between vitamin D and three markers of arterial dysfunction among HIV-infected individuals on stable antiretroviral (ARV) therapy. Levels of 25-hydroxyvitamin D [25(OH)D] were assessed by chemiluminescent immunoassay (DiaSorin) in 100 enrollees into the Hawaii Aging with HIV-Cardiovascular Cohort Study, a cohort of HIV-infected subjects age ≥40 years on stable (≥6 months) ARV therapy. The relationships between 25(OH)D levels and brachial artery flow-mediated dilation (FMD), right common carotid artery intima-media thickness (cIMT), and coronary artery calcium (CAC) were examined. Analytical methods included Pearson's correlations, Kruskal–Wallis tests, relative risks, and linear regression models. The cohort was 86% male and 60% white with a median age of 52 years and CD4 of 510 cells/mm3. The median (Q1, Q3) level of 25(OH)D was 27.9 ng/ml (21.8, 38.3). There were 72 FMD, 50 cIMT, and 90 CAC measurements available for analyses. A significant correlation was observed between 25(OH)D levels and FMD (r=0.30, p=0.01) but not with cIMT (r=−0.05, p=0.76). In a linear regression model, Framingham risk score attenuated the relationship between FMD and 25(OH)D. Those with lower 25(OH)D levels were at slightly higher risk of having CAC (RR=1.02, p=0.04). Among those with CAC, lower 25(OH)D levels were not associated with higher CAC scores (p=0.36). Lower vitamin D levels are associated with evidence of subclinical arterial dysfunction in HIV-infected individuals. The significance of these findings warrants further investigation.
doi:10.1089/aid.2011.0086
PMCID: PMC3399561  PMID: 21978287
13.  Coffee, Decaffeinated Coffee, Caffeine, and Tea Consumption in Young Adulthood and Atherosclerosis Later in Life: The CARDIA Study 
Objective
Determine the association of coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood with the presence and progression of coronary artery calcified (CAC) plaque and carotid intima-media thickness (cIMT) later in life.
Methods and Results
CARDIA is a cohort of 5115 white and black adults who were 18–30 years when they completed a baseline clinic examination in 1985–1986. Subsequent examinations were conducted 2, 5, 7, 10, 15, and 20 years later. After multivariable adjustment, no association was observed between average coffee, decaffeinated coffee, or caffeine consumption (years 0 and 7) and presence of CAC [score >0 Agatston units (AU) at year 15 or 20], CAC progression (incident CAC at year 20 or an increase in CAC score ≥20 AU), or high cIMT (>80th percentile, year 20). Tea consumption, however, displayed a non-significant trend for an inverse association with CAC (ptrend0.08) and an inverse association with CAC progression (ptrend0.04), but no association with high cIMT (ptrend>0.2). Stratification of the coffee analyses by sex, race, or smoking yielded similar non-significant patterns.
Conclusion
We observed no substantial association between coffee or caffeine intake and coronary and carotid atherosclerosis. However, our results suggested an inverse association between tea and CAC, but not carotid atherosclerosis.
doi:10.1161/ATVBAHA.110.208280
PMCID: PMC2940975  PMID: 20616310
antioxidants; atherosclerosis; carotid arteries; diet; epidemiology; nutrition
14.  Circulating Vitamin D Metabolites and Subclinical Atherosclerosis in Type 1 Diabetes 
Diabetes Care  2013;36(8):2423-2429.
OBJECTIVE
People with type 1 diabetes are at high risk of premature atherosclerosis. Existing evidence suggests that impaired vitamin D metabolism may contribute to the development of atherosclerosis. We tested associations of circulating vitamin D metabolite concentrations with subclinical atherosclerosis among 1,193 participants with type 1 diabetes in the DCCT/EDIC study.
RESEARCH DESIGN AND METHODS
We measured plasma concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D by mass spectrometry at the end of the DCCT. In a staggered cross-sectional design, we tested associations with coronary artery calcium (CAC), measured by computed tomography a median of 10 years later, and with common and internal carotid intima-media thickness (IMT), measured by B-mode ultrasonography on two occasions a median of 4 years later and a median of 10 years later. We hypothesized that lower concentrations of each vitamin D metabolite would be associated with increased risk of CAC and greater carotid IMT.
RESULTS
At the time metabolites were measured, mean age was 32.4 years and mean duration of diabetes was 7.5 years. The prevalence and severity of CAC tended to be lower—not higher—with lower concentrations of each vitamin D metabolite. For instance, in a fully adjusted multinomial logistic model, a 25 nmol/L lower 25-hydroxyvitamin D was associated with a 0.8-fold decrease in the odds of having higher CAC (95% CI 0.68–0.96, P = 0.01). No vitamin D metabolite was associated with either common or internal mean IMT.
CONCLUSIONS
We did not find evidence linking impaired vitamin D metabolism with increased subclinical atherosclerosis in type 1 diabetes.
doi:10.2337/dc12-2020
PMCID: PMC3714470  PMID: 23530012
15.  Is Diabetic Retinopathy Related to Subclinical Cardiovascular Disease? 
Ophthalmology  2010;118(5):860-865.
OBJECTIVE
Persons with diabetic retinopathy (DR) have an increased risk of clinical cardiovascular events. Our study aimed to determine whether DR is associated with a range of measures of subclinical cardiovascular disease (CVD) in persons without clinical CVD.
DESIGN
Population-based, cross-sectional epidemiologic study
PARTICIPANTS
Nine hundred and twenty seven persons with diabetes without clinical CVD in the Multi-Ethnic Study of Atherosclerosis.
METHODS
DR was ascertained from retinal photographs according to modification of the Airlie House Classification system. Vision threatening DR (VTDR) was defined as severe non-proliferative DR, proliferative DR or clinically significant macular edema. Subclinical CVD measures were assessed and defined as follows: high coronary artery calcium (CAC) score, defined as CAC score≥400; low ankle-brachial index (ABI), defined as ABI<0.9; high ABI, defined as ABI≥1.4; high carotid intima-media thickness (IMT), defined as highest 25% of IMT; and carotid stenosis, defined as >25% stenosis or presence of carotid plaque.
MAIN OUTCOME MEASURES
Associations between DR and subclinical CVD measures.
RESULTS
The prevalence of DR and VTDR in this sample was 30.0% and 7.2%, respectively. VTDR was associated with a high CAC score (odds ratio [OR] 2.33, 95% condifence interval [CI] 1.15–4.73), low ABI (OR 2.54; 95%CI, 1.08–5.99) and high ABI (OR 12.6, 95% CI, 1.14, 140.6), after adjusting for risk factors including hemoglobin A1c level and duration of diabetes. The association between VTDR and high CAC score remained significant after further adjustment for hypoglycemic, anti-hypertensive and cholesterol-lowering medications. DR was not significantly associated with measures of carotid artery disease.
CONCLUSIONS
In persons with diabetes without a history of clinical CVD, the presence of advanced stage of DR is associated with subclinical coronary artery disease. These findings emphasize the need to be careful about the use of anti-vascular endothelial growth factor for the treatment of DR.
doi:10.1016/j.ophtha.2010.08.040
PMCID: PMC3087839  PMID: 21168222
16.  Tissue factor pathway inhibitor, vascular risk factors and subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis 
Atherosclerosis  2009;207(1):277-283.
Background
Tissue factor pathway inhibitor (TFPI) is an endothelial membrane-associated anticoagulant protein. Higher circulating levels might reflect endothelial damage.
Objective
We hypothesized an association of higher total TFPI with subclinical atherosclerosis.
Patients/Methods
Total TFPI was measured in 1000 participants of the Multi-Ethnic Study of Atherosclerosis, a cohort of 6814 men and women without clinical vascular disease, aged 45–84, from 4 ethnic groups. Subclinical atherosclerosis measures were coronary artery calcium (CAC), carotid intima-media thickness (IMT) and ankle-brachial index (ABI).
Results
TFPI was higher with age, male gender, higher LDL-cholesterol, smoking and diabetes, but not ethnicity. Adjusting for risk factors, TFPI in the 4th versus 1st quartile was associated with a 1.2-fold increased risk of detectable CAC (95% CI 1.0–1.4), a 2.1-fold increased risk of CAC >400 Agatston units (95% CI 1.1–4.0) and a 1.6-fold (95% CI 1.1–2.5) increased risk of internal carotid IMT above the 80th percentile, but not with external carotid IMT or low ABI. Findings were consistent across ethnic groups.
Conclusions
In this diverse population, higher total TFPI was associated with prevalent CAC (limited to levels >400 units), and elevated internal carotid IMT, independent of other factors. Higher TFPI may indicate endothelial dysfunction. Further study is needed of TFPI and progression of atherosclerosis.
doi:10.1016/j.atherosclerosis.2009.04.024
PMCID: PMC2784263  PMID: 19467658
atherosclerosis; coronary heart disease; tissue factor pathway inhibitor; risk factor
17.  Associations between markers of subclinical atherosclerosis and dietary patterns derived by principal components analysis and reduced rank regression in the Multi-Ethnic Study of Atherosclerosis (MESA)1–3 
Background
The association between diet and cardiovascular disease (CVD) may be mediated partly through inflammatory processes and reflected by markers of subclinical atherosclerosis.
Objective
We investigated whether empirically derived dietary patterns are associated with coronary artery calcium (CAC) and common and internal carotid artery intima media thickness (IMT) and whether prior information about inflammatory processes would increase the strength of the associations.
Design
At baseline, dietary patterns were derived with the use of a food-frequency questionnaire, and inflammatory biomarkers, CAC, and IMT were measured in 5089 participants aged 45–84 y, who had no clinical CVD or diabetes, in the Multi-Ethnic Study of Atherosclerosis. Dietary patterns based on variations in C-reactive protein, interleukin-6, homocysteine, and fibrinogen concentrations were created with reduced rank regression (RRR). Dietary patterns based on variations in food group intake were created with principal components analysis (PCA).
Results
The primary RRR(RRR 1) and PCA(PCA factor 1) dietary patterns were high in total and saturated fat and low in fiber and micronutrients. However, the food sources of these nutrients differed between the dietary patterns. RRR 1 was positively associated with CAC [Agatston score >0: OR(95% CI) for quartile 5 compared with quartile 1 = 1.34 (1.05, 1.71); ln(Agatston score = 1): P for trend = 0.023] and with common carotid IMT [≥1.0 mm: OR (95% CI) for quartile 5 compared with quartile 1 = 1.33 (0.99, 1.79); ln(common carotid IMT): P for trend = 0.006]. PCA 1 was not associated with CAC or IMT.
Conclusion
The results suggest that subtle differences in dietary pattern composition, realized by incorporating measures of inflammatory processes, affect associations with markers of subclinical atherosclerosis.
PMCID: PMC2858465  PMID: 17556701
Dietary patterns; principal components analysis; reduced rank regression; carotid artery intima media thickness; coronary artery calcium
18.  Circulating soluble ICAM-1 and subclinical atherosclerosis: The Coronary Artery Risk Development in Young Adults (CARDIA) Study 
Clinical chemistry  2011;58(2):10.1373/clinchem.2011.168559.
Background
Soluble intercellular adhesion molecule-1 (sICAM-1) is associated with endothelial dysfunction and clinical cardiovascular disease. We investigated the relationship of subclinical atherosclerosis with sICAM-1 concentration.
Methods
sICAM-1 concentration was assayed at year 15 of the Coronary Artery Risk Development in Young Adults (CARDIA) Study (black and white men and women, average age 40 years). We assessed progression of coronary artery calcification through year 20 (CAC, n=2378), and both carotid artery stenosis (n=2432) and intima media thickness at year 20 (IMT, n = 2240).
Results
Median sICAM-1 was 145.9 ng/ml. Among a subgroup with advanced atherosclerotic plaque (either CAC or stenosis), IMT was 0.010 (95% confidence interval (CI) 0.003–0.017 mm) higher per standard deviation of sICAM-1 (44 ng/ml) in a model adjusted for age, race, sex, clinic, smoking, exercise, body size, education, blood pressure, antihypertensive medication, plasma lipids, and cholesterol lowering medication. With the same adjustment, the odds ratios (OR) for the presence of year 20 carotid artery stenosis per SD of sICAM-1 was 1.12 (CI 1.01–1.25, p<0.04), while for occurrence of CAC progression the OR was 1.16 (CI 1.04–1.31, p<0.01). The associations with CAC and carotid stenosis were strongest in the top 20th of the sICAM-1 distribution.
Conclusion
sICAM-1 concentration may be an early biomarker that indicates changes in the artery wall that accompany atherosclerosis, as well as the presence of advanced plaque in the coronary and carotid arteries. This finding holds in people with low total burden of atherosclerosis, decades prior to the development of clinical CVD.
doi:10.1373/clinchem.2011.168559
PMCID: PMC3867124  PMID: 22179741
19.  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 ≥8.5 µmol/L enrolled in the BVAIT study (n=504, mean age 61 years). Carotid artery intima-media thickness (CIMT), coronary (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 (β = −0.07 per 0.1 mm increase CIMT [SE(β)=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 but without clinically evident CVD. The association between CIMT and poor verbal learning may pertain particularly to men.
doi:10.1002/gps.2134
PMCID: PMC2661006  PMID: 18836986
cognitive function; atherosclerosis; cardiovascular disease; memory; verbal learning
20.  Calcium Density of Coronary Artery Plaque and Risk of Incident Cardiovascular Events 
Importance
Coronary artery calcium (CAC), measured by computed tomography (CT), has strong predictive value for incident cardiovascular disease (CVD) events. The standard CAC score is the Agatston, which is weighted upward for greater calcium density. However, some data suggest increased plaque calcium density may be protective for CVD.
Objective
To determine the independent associations of CAC volume and CAC density with incident CVD events.
Design, Setting, and Participants
Multicenter, prospective observational MESA study (Multi-Ethnic Study of Atherosclerosis), conducted at 6 US field centers of 3398 men and women from 4 race/ethnicity groups; non-Hispanic white, African American, Hispanic, and Chinese. Participants were aged 45-84 years, free of known CVD at baseline, had CAC greater than 0 on their baseline CT, and were followed up through October 2010.
Main Outcomes and Measures
Incident coronary heart disease (CHD) and all CVD events
Results
During a median of 7.6 years of follow-up, there were 175 CHD events and an additional 90 other CVD events for a total of 265 CVD events. With both lnCAC volume and CAC density scores in the same multivariable model, the lnCAC volume score showed an independent association with incident CHD, with a hazard ratio (HR) of 1.81 (95% CI, 1.47-2.23) per standard deviation (SD = 1.6) increase, absolute risk increase 6.1 per 1000 person-years, and for CVD an HR of 1.68 (95% CI, 1.42-1.98) per SD increase, absolute risk increase 7.9 per 1000 person-years. Conversely, the CAC density score showed an independent inverse association, with an HR of 0.73 (95% CI, 0.58-0.91) per SD (SD = 0.7) increase for CHD, absolute risk decrease 5.5 per 1000 person-years, and an HR of 0.71 (95% CI, 0.60-0.85) per SD increase for CVD, absolute risk decrease 8.2 per 1000 person years. Area under the receiver operating characteristic curve analyses showed significantly improved risk prediction with the addition of the density score to a model containing the volume score for both CHD and CVD. In the intermediate CVD risk group, the area under the curve for CVD increased from 0.53 (95% CI, 0.48-0.59) to 0.59 (95% CI, 0.54-0.64), P = .02.
Conclusions and Relevance
CAC volume was positively and independently associated with CHD and CVD risk. At any level of CAC volume, CAC density was inversely and significantly associated with CHD and CVD risk. The role of CAC density should be considered when evaluating current CAC scoring systems.
doi:10.1001/jama.2013.282535
PMCID: PMC4091626  PMID: 24247483
21.  Metabolic Syndrome and Subclinical Atherosclerosis in Patients Infected with HIV 
Background
The present study examines the association between carotid and coronary atherosclerosis and metabolic syndrome in human immunodeficiency virus (HIV)–infected adults.
Methods
We measured the common and internal carotid intima-media thickness (c-IMT) using B-mode ultrasonography, and we measured coronary artery calcium (CAC) using high-resolution, electrocardiographic, synchronized, computed tomography, for 314 HIV-infected men and women. Metabolic syndrome was defined by National Cholesterol Education Program/Adult Treatment Panel III criteria. We compared the c-IMT measurements and CAC scores of patients with metabolic syndrome with the scores of those without metabolic syndrome using a Wilcoxon test for continuous variables and a χ2 test for categorical variables. To examine the association between surrogate markers and metabolic syndrome, we used logistic regression analysis.
Results
Participants with metabolic syndrome were more likely to have a common c-IMT measurement >0.8 mm than were those without metabolic syndrome (17% vs.7%; P=.009), but both groups were equally likely to have an internal c-IMT measurement >1.0 mm (20% vs. 13%; P=.15). Any positive CAC score was more likely to occur for participants with metabolic syndrome (80.3% vs. 46.7%; P < .0001). In a multivariate model adjusted for sex, age, ethnicity, and smoking status, participants with metabolic syndrome were more likely than those without metabolic syndrome to have an abnormal common c-IMT measurement (odds ratio [OR], 2.9; P= .020) and detectable CAC scores (OR, 4.9; P < .0001) but not a higher internal c-IMT measurement (OR, 1.6; P=.255).
Conclusion
Our study demonstrates that HIV-infected individuals with metabolic syndrome may be at increased risk for subclinical atherosclerosis and supports screening for metabolic syndrome among HIV-infected patients at risk for cardiovascular disease.
doi:10.1086/516616
PMCID: PMC2745593  PMID: 17443477
22.  Metabolic Syndrome, Diabetes, and Incidence and Progression of Coronary Calcium: The Multiethnic Study of Atherosclerosis (MESA) 
Jacc. Cardiovascular Imaging  2012;5(4):358-366.
Objectives
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.
Background
MetS and DM are associated with subclinical atherosclerosis as evidenced by coronary artery calcium (CAC).
Methods
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.
Results
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).
Conclusions
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.
doi:10.1016/j.jcmg.2011.12.015
PMCID: PMC3327555  PMID: 22498324
atherosclerosis; diabetes; risk factors; calcification
23.  Association of Fat Density With Subclinical Atherosclerosis 
Background
Ectopic fat density is associated with cardiovascular disease (CVD) risk factors above and beyond fat volume. Volumetric measures of ectopic fat have been associated with CVD risk factors and subclinical atherosclerosis. The aim of this study was to investigate the association between fat density and subclinical atherosclerosis.
Methods and Results
Participants were drawn from the Multi‐Detector Computed Tomography (MDCT) substudy of the Framingham Heart Study (n=3079; mean age, 50.1 years; 49.2% women). Fat density was indirectly estimated by computed tomography attenuation (Hounsfield Units [HU]) on abdominal scan slices. Visceral fat (VAT), subcutaneous fat (SAT), and pericardial fat HU and volumes were quantified using standard protocols; coronary and abdominal aortic calcium (CAC and AAC, respectively) were measured radiographically. Multivariable‐adjusted logistic regression models were used to evaluate the association between adipose tissue HU and the presence of CAC and AAC. Overall, 17.1% of the participants had elevated CAC (Agatston score [AS]>100), and 23.3% had elevated AAC (AS>age‐/sex‐specific cutoffs). Per 5‐unit decrement in VAT HU, the odds ratio (OR) for elevated CAC was 0.76 (95% confidence interval [CI], 0.65 to 0.89; P=0.0005), even after adjustment for body mass index or VAT volume. Results were similar for SAT HU. With decreasing VAT HU, we also observed an OR of 0.79 (95% CI, 0.67 to 0.92; P=0.004) for elevated AAC after multivariable adjustment. We found no significant associations between SAT HU and AAC. There was no significant association between pericardial fat HU and either CAC or AAC.
Conclusions
Lower VAT and SAT HU, indirect estimates of fat quality, are associated with a lower risk of subclinical atherosclerosis.
doi:10.1161/JAHA.114.000788
PMCID: PMC4310364  PMID: 25169793
atherosclerosis; epidemiology; fat density; obesity
24.  Inflammation induces fibrinogen nitration in experimental human endotoxemia 
Free radical biology & medicine  2009;47(8):1140-1146.
Elevated plasma fibrinogen is a prothrombotic risk factor for cardiovascular disease (CVD). Recent small studies report that fibrinogen oxidative modifications, specifically tyrosine residue nitration, can occur in inflammatory states and may modify fibrinogen function. HDL cholesterol is inversely related to CVD and suggested to reduce the oxidation of LDL cholesterol, but whether these antioxidant functions extend to fibrinogen modifications is unknown. We used a recently validated ELISA to quantify nitrated fibrinogen during experimental human endotoxemia (N=23) and in a cohort of healthy adults (N=361) who were characterized for inflammatory and HDL parameters as well as subclinical atherosclerosis measures, carotid artery intima-medial thickness (IMT) and coronary artery calcification (CAC). Fibrinogen nitration increased following endotoxemia and directly correlated with accelerated ex vivo plasma clotting velocity. In the observational cohort, nitrated fibrinogen was associated with levels of CRP and serum amyloid A. Nitrated fibrinogen levels were not lower with increasing HDL cholesterol and did not associate with IMT and CAC. In humans, fibrinogen nitration was induced during inflammation and was correlated with markers of inflammation and clotting function but not HDL cholesterol or subclinical atherosclerosis in our modest sample. Inflammation-induced fibrinogen nitration may be a risk factor for promoting CVD events.
doi:10.1016/j.freeradbiomed.2009.07.025
PMCID: PMC3651370  PMID: 19631267
Fibrinogen; Nitration; Intima-medial thickness; Coronary artery calcification; High-density lipoprotein (HDL)
25.  The Association Between A1C and Subclinical Cardiovascular Disease 
Diabetes Care  2009;32(9):1727-1733.
OBJECTIVE
To test the hypothesis that A1C is associated with subclinical cardiovascular disease (CVD) in a population without evident diabetes, after adjusting for traditional CVD risk factors and BMI.
RESEARCH DESIGN AND METHODS
This was a cross-sectional study of 5,121 participants without clinically evident CVD or diabetes (fasting glucose ≥7.0 mmol/l or use of diabetes medication), aged 47–86 years, enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Measurements included carotid intimal-medial wall thickness (CIMT) and coronary artery calcification (CAC). Results were adjusted for age, sex, ethnicity, smoking, systolic blood pressure, LDL cholesterol, HDL cholesterol, antihypertensive medication use, lipid-lowering medication use, and BMI.
RESULTS
Compared with those in the lowest quartile for A1C ([mean ± SD] 5.0 ± 0.2%), participants in the highest quartile (6.0 ± 0.3%) had higher adjusted mean values for common CIMT (0.85 vs. 0.87 mm, P = 0.003) and internal CIMT (1.01 vs. 1.08 mm, P = 0.003). A1C quartile was not associated with prevalence of CAC in the entire cohort (P = 0.27); however, the association was statistically significant in women (adjusted prevalence of CAC in lowest and highest A1C quartiles 37.5 vs. 43.0%, P = 0.01). Among those with some CAC, higher A1C quartile tended to be associated with higher CAC score, but the results were not statistically significant (adjusted P = 0.11).
CONCLUSIONS
In this multiethnic cohort, there were small, positive associations between A1C, common CIMT, and internal CIMT in the absence of clinically evident diabetes. An association between higher A1C and CAC prevalence was evident only in women.
doi:10.2337/dc09-0074
PMCID: PMC2732160  PMID: 19549732

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