Persistent Asthma Is Associated With Carotid Plaque in MESA.

Background Asthma and atherosclerotic cardiovascular disease share an underlying inflammatory pathophysiology. We hypothesized that persistent asthma is associated with carotid plaque burden, a strong predictor of atherosclerotic cardiovascular disease events. Methods and Results The MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults free of known atherosclerotic cardiovascular disease at baseline. Subtype of asthma was determined at examination 1. Persistent asthma was defined as asthma requiring use of controller medications, and intermittent asthma was defined as asthma without controller medications. B-mode carotid ultrasound was performed to detect carotid plaques (total plaque score [TPS], range 0-12). Multivariable regression modeling with robust variances evaluated the association of asthma subtype and carotid plaque burden. The 5029 participants were a mean (SD) age of 61.6 (10.0) years (53% were women, 26% were Black individuals, 23% were Hispanic individuals, and 12% were Chinese individuals). Carotid plaque was present in 50.5% of participants without asthma (TPS, 1.29 [1.80]), 49.5% of participants with intermittent asthma (TPS, 1.25 [1.76]), and 67% of participants with persistent asthma (TPS, 2.08 [2.35]) (P≤0.003). Participants with persistent asthma had higher interleukin-6 (1.89 [1.61] pg/mL) than participants without asthma (1.52 [1.21] pg/mL; P=0.02). In fully adjusted models, persistent asthma was associated with carotid plaque presence (odds ratio, 1.83 [95% confidence interval, 1.21-2.76]; P<0.001) and TPS (ß=0.66; P<0.01), without attenuation after adjustment for baseline interleukin-6 (P=0.02) or CRP (C-reactive protein) (P=0.01). Conclusions Participants with persistent asthma had higher carotid plaque burden and higher levels of inflammatory biomarkers, compared with participants without asthma. Adjustment for baseline inflammatory biomarkers did not attenuate the association between carotid plaque and asthma subtype, highlighting the increased atherosclerotic cardiovascular disease risk among those with persistent asthma may be multifactorial.

HIV indirectly accelerates coronary artery disease by promoting the effects of risk factors: longitudinal observational study.

Our objective was to assess whether human immunodeficiency virus (HIV)-infection directly or indirectly promotes the progression of clinical characteristics of coronary artery disease (CAD). 300 African Americans with asymptomatic CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV-infected) who underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years) were randomly selected from 1429 participants of a prospective epidemiological study between May 2004 and August 2015. We calculated Agatston-scores, number of coronary plaques and segment stenosis score (SSS). Linear mixed models were used to assess the effects of HIV-infection, atherosclerotic cardiovascular disease (ASCVD) risk, years of cocaine use on CAD. There was no significant difference in annual progression rates between HIV-infected and-uninfected regarding Agatston-scores (10.8 ± 25.1/year vs. 7.2 ± 17.8/year, p = 0.17), the number of plaques (0.2 ± 0.3/year vs. 0.3 ± 0.5/year, p = 0.11) or SSS (0.5 ± 0.8/year vs. 0.5 ± 1.3/year, p = 0.96). Multivariately, HIV-infection was not associated with Agatston-scores (8.3, CI: [- 37.2-53.7], p = 0.72), the number of coronary plaques (- 0.1, CI: [- 0.5-0.4], p = 0.73) or SSS (- 0.1, CI: [- 1.0-0.8], p = 0.84). ASCVD risk scores and years of cocaine-use significantly increased all CAD outcomes among HIV-infected individuals, but not among HIV-uninfected. Importantly, none of the HIV-medications were associated with any of the CAD outcomes. HIV-infection is not directly associated with CAD and therefore HIV-infected are not destined to have worse CAD profiles. However, HIV-infection may indirectly promote CAD progression as risk factors may have a more prominent role in the acceleration of CAD in these patients.

Ethnic Differences in the Pathobiology of Acute Coronary Syndromes Between Asians and Whites.

Ethnic differences in the pathobiology of acute coronary syndromes (ACS) have not been systematically studied. We compared the underlying mechanisms of ACS between Asians and Whites. ACS patients with the culprit lesion imaged by optical coherence tomography were included. Patients were stratified into ST-elevation myocardial infarction (STEMI) and non-ST-elevation-ACS (NSTE-ACS), and baseline characteristics, underlying mechanisms of ACS, and culprit plaque characteristics were compared between Asians and Whites. Of 1,225 patients, 1,019 were Asian (567 STEMI and 452 NSTE-ACS) and 206 were White (71 STEMI and 135 NSTE-ACS). Asians had more diabetes and hypertension among STEMI patients; among NSTE-ACS patients, Asians had higher prevalence of diabetes and renal insufficiency, and lower prevalence of hyperlipidemia. There were no differences in the incidence of plaque rupture, plaque erosion and calcified plaque between Asians and Whites with STEMI (61.2%, 28.6%, 10.2% vs 46.5%, 38.0%, 15.5%, respectively, p = 0.055). Among NSTE-ACS patients, there was a significant difference between Asians and Whites (40.5%, 47.6%, 11.9% vs 27.4%, 48.9%, 23.7%, respectively, p = 0.001). After adjustment for clinical confounders, the risk of plaque rupture (p = 0.713), plaque erosion (p = 0.636), and calcified plaque (p = 0.986) was similar between the groups with STEMI. In NSTE-ACS patients, the only difference was an increased risk of calcified plaque in Whites (odds ratio: 2.125, 95% confidence interval: 1.213 to 3.723, p = 0.008). In conclusion, after adjustment for clinical confounders, Asian and White patients presenting with STEMI and NSTE-ACS showed similar underlying mechanisms of ACS, except for a higher risk of calcified plaque in Whites with NSTE-ACS.

Comparison of Coronary Atherosclerotic Plaque Burden and Composition as Assessed on Coronary Computed Tomography Angiography in East Asian and European-Origin Caucasians.

Recent evidence suggests plaque morphology evaluated on coronary computed tomography angiography has prognostic implications. East Asians have a lower prevalence of myocardial infarction and cardiovascular mortality compared with European-origin Caucasians. We aimed to compare coronary atherosclerotic burden and plaque composition in a matched cohort of Caucasian and East Asians patients with stable chest pain who underwent computed tomography angiography. Two-hundred symptomatic patients (age 58.8 ± 7.9, male 51%) were matched for age, gender, body mass index, and diabetes (100 each ethnic group). A blinded core-laboratory quantified calcified and noncalcified plaque (NCP) volume and burden. Components of NCP were differentiated by plaque hounsfield unit (HU) thresholds which defined high-risk necrotic core (-30 to 30HU), fibrofatty plaque (31 to 130HU); and low-risk fibrous plaque (131 to 350HU). Composition of NCP components was derived as (NCP component volume/total NCP volume) × 100%. Segment Involvement Score, percent diameter and area stenosis were comparable in both groups. Similarly, there was no difference in the volume and burden of total, calcified and NCP. Compared with Caucasians, East Asians demonstrated lower composition of plaque attenuation corresponding to necrotic core (3.5 vs 5.1%; p = 0.004) and fibrofatty plaque (29.6 vs 37.3%; p = 0.005), and higher fibrous plaque (65.7 vs 57.6%; p = 0.004). On multivariable analysis East Asian ethnicity was independently associated with lower composition of high-risk plaque after adjustment for risk factors and scan parameters. These findings were consistent in a propensity-matched sensitivity-analysis. In conclusion, based on this matched cohort, East Asian ethnicity is associated with significantly less composition of high-risk NCP (necrotic core and fibrofatty plaque) and a higher composition of low-risk fibrous plaque compared with Caucasians; which may confer a lower risk of cardiovascular events.

Race-Based Differences in Lipoprotein(a)-Associated Risk of Carotid Atherosclerosis.

Objective- Lp(a) [lipoprotein(a)] is a well-described risk factor for atherosclerosis, but Lp(a)-associated risk may vary by race/ethnicity. We aimed to determine whether race/ethnicity modifies Lp(a)-related risk of carotid atherosclerotic plaque outcomes among black, white, Chinese, and Hispanic individuals. Approach and Results- Carotid plaque presence and score were assessed by ultrasonography at baseline (n=5155) and following a median 9.4 year period (n=3380) in MESA (Multi-Ethnic Study of Atherosclerosis) participants. Lp(a) concentrations were measured by immunoassay and examined as a continuous and categorical variable using clinically-based cutoffs, 30 and 50 mg/dL. Lp(a) was related to greater risk of prevalent carotid plaque at baseline in whites alone (all P<0.001): per log unit (relative risk, 1.05); Lp(a)≥30 mg/dL (relative risk, 1.16); and Lp(a)≥50 mg/dL (relative risk, 1.20). Lp(a) levels over 50 mg/dL were associated with a higher plaque score at baseline in whites (all P<0.001) and Hispanics ( P=0.04). In prospective analyses, whites with Lp(a) ≥50 mg/dL were found to have greater risk of plaque progression (relative risk, 1.12; P=0.03) and higher plaque scores (all P<0.001) over the 9.4-year follow-up. Race-based differences between whites and black participants were significant for cross-sectional associations and for carotid plaque score following the 9.4 year study period. Conclusions- Race was found to be a modifying variable in Lp(a)-related risk of carotid plaque, and Lp(a) levels may have greater influence on plaque burden in whites than in black individuals. Borderline results in Hispanics suggest that elevated Lp(a) may increase the risk of carotid plaque, but follow-up studies are needed.

Intracranial artery stenosis magnetic resonance imaging aetiology and progression study: Rationale and design.

BACKGROUND: It has been shown that intracranial artery stenosis (ICAS) plays a key role in Chinese ischemic stroke or transient ischemic attack (TIA) patients. Many vascular diseases can lead to ICAS, such as atherosclerosis, dissection, vasculitis, moyamoya disease, and reversible cerebral vasoconstriction syndrome (RCVS). In addition, progression of intracranial atherosclerotic disease (ICAD) will increase the risk of ischemic cerebrovascular events. The ICASMAP study primarily aims to determine the etiology and disease distribution of ICAS using noninvasive magnetic resonance (MR) imaging and evaluate the rate for progression of ICAD in symptomatic population. METHODS: The ICASMAP study is a prospective, observational, and multicenter study by recruiting 300 subjects (18-80 years old) with recent stroke or TIA (within 2 weeks after onset of symptoms) in China. All the subjects will undergo MR imaging examination including brain and intracranial artery MR imaging at baseline. In addition, the clinical risk factors will be collected and blood biomarkers will be tested. A subgroup of more than 200 subjects who were diagnosed with ICAD according to baseline MR imaging will be followed up for 2 years. During the follow-up study, MR imaging examination will be performed at 12 and 24 months. The primary end point is presence of progression of intracranial artery atherosclerotic plaques. CONCLUSIONS: The ICASMAP study investigates the etiology of ICAS and progression of ICAD in Chinese stroke patients and may help to improve the precise diagnosis and intervention of ICAS and stroke prevention.

Comparison of carotid plaque burden among healthy middle-aged men living in the US, Japan, and South Korea.

BACKGROUND: Carotid plaque has emerged as a marker of coronary heart disease (CHD) risk. Comparison of carotid plaque burden between different race/ethnic groups may provide a relative estimate of their future CHD risk. METHODS: We conducted a population-based study among apparently healthy middle-aged men aged 40-49 years (ERA JUMP study (n = 924)) and recruited 310 Whites in Pittsburgh, US, 313 Japanese in Otsu, Japan, and 301 Koreans in Ansan, South Korea. The number of carotid plaque and CHD risk factors was assessed using a standardized protocol across all centers. The burden of carotid plaque was compared between race/ethnic groups after adjustment for age and BMI, and after multivariable adjustment for other CHD risk factors using marginalized zero-inflated Poisson regression models. Cross-sectional associations of risk factors with plaque were examined. RESULTS: Whites (22.8%) had more than four-fold higher prevalence (p < 0.01) of carotid plaque than Japanese men (4.8%) while the prevalence among Koreans was 10.6%. These differences remained significant after adjustment for age, BMI as well as other risk factors - incidence density ratio (95% confidence interval) for plaque was 0.13 (0.07, 0.24) for Japanese and 0.32 (0.18, 0.58) for Koreans as compared to Whites. Age, hypertension and diabetes were the only risk factors significantly associated with presence of carotid plaque in the overall population. CONCLUSION: Whites have significantly higher carotid plaque burden than men in Japan and Korea. Lower carotid plaque burden among Japanese and Koreans is independent of traditional CVD risk factors.

Racial Differences in Prevalence and Risk for Intracranial Atherosclerosis in a US Community-Based Population.

Importance: Intracranial atherosclerotic disease (ICAD) is an important cause of stroke; however, little is known about racial differences in ICAD prevalence and its risk factors. Objective: To determine racial differences in ICAD prevalence and the risk factors (both midlife and concurrent) associated with its development in a large, US community-based cohort. Design, Setting, and Participants: Analysis of 1752 black and white participants recruited from the Atherosclerosis Risk in Communities (ARIC) cohort study who underwent 3-dimensional intracranial vessel wall magnetic resonance imaging from October 18, 2011 to December 30, 2013; data analysis was performed from October 18, 2011 to May 13, 2015. Exposures: Midlife and concurrent cardiovascular risk factors. Main Outcomes and Measures: Intracranial plaque presence, size (maximum normalized wall index) and number were assessed by vessel wall magnetic resonance imaging. Midlife and concurrent vascular risk factor associations were determined by Poisson regression (plaque presence), negative binominal regression (plaque number), and linear regression (plaque size), and compared between races. Results: Of the 1752 study participants (mean [SD] age, 77.6 [5.3] years; range, 67-90 years), 1023 (58.4%) were women and 518 (29.6%) were black. Black men had the highest prevalence (50.9% vs 35.9% for black women, 35.5% for white men, and 30.2% for white women; P < .001) and the highest frequency (22.4% vs 12.1% for black women, 10.7% for white men, and 8.7% for white women; P < .01) of multiple plaques. Prevalence increased with age, reaching 50% before ages 68, 84, and 88 years in black men, white men, and white women, respectively (ICAD prevalence remained <50% in black women). Midlife hypertension and hyperlipidemia were associated with 29% (prevalence ratio [PR], 1.29; 95% CI, 1.08-1.55) and 18% (PR, 1.18; 95% CI, 0.98-1.42), respectively, increased ICAD prevalence with no significant differences between races. Midlife hypertension was also associated with larger plaques (1.11 higher mean maximum normalized wall index; 95% CI, 0.21-2.01). Midlife smoking and diabetes were associated with increased risk of ICAD in black individuals (102% [PR, 2.02; 95% CI, 1.12-3.63] and 57% [PR, 1.57; 95% CI, 1.13- 2.19], respectively), but not in white participants (P < .05 interaction by race). Conclusions and Relevance: The prevalence of ICAD was highest in black men. Midlife smoking and diabetes were strongly associated with late-life ICAD in blacks only, whereas midlife hypertension and hyperlipidemia were associated with late-life ICAD in both races. These associations may help to explain racial differences in US stroke rates and offer insight into preventive risk-factor management strategies.

Comparison of Carotid Plaque Score and Coronary Artery Calcium Score for Predicting Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Coronary artery calcium (CAC) predicts coronary heart disease (CHD) events better than carotid wall plaque presence; however, differences in the utility of CAC burden and carotid plaque burden across the spectrum of cardiovascular disease (CVD) events is unknown. METHODS AND RESULTS: CVD, CHD and stroke/transient ischemic attack (TIA) events were evaluated prospectively in a multiethnic cohort without CVD at baseline. Carotid plaque score was determined by the number of ultrasound-detected plaques in the common, bifurcation, and internal carotid artery segments. CAC was detected by computed tomography. Predictive values were compared using Cox proportional hazards models, C-statistics, and net reclassification, adjusting for traditional CVD risk factors. At baseline, the 4955 participants were mean (SD) 61.6 (10.1) years old and 52.8% female; 48.9% had CAC >0 and 50.8% had at least 1 carotid plaque. After 11.3 (3.0) years of follow-up, 709 CVD, 498 CHD, and 262 stroke/TIA events occurred. CAC score compared to carotid plaque score was a stronger predictor of CVD (hazard ratio [HR], 1.78; 95% CI, 1.16-1.98; P<0.001 vs HR, 1.27; 95% CI, 1.16-1.40; P<0.001) and CHD events (HR, 2.09; 95% CI, 1.84-2.38; P<0.001 vs HR, 1.35; 95% CI, 1.21-1.51; P<0.001). CAC score and carotid plaque score were weak predictors of stroke/TIA. CAC score had better reclassification statistics than carotid plaque score, except for stroke/TIA, which had similar predictive values. CONCLUSIONS: CAC score improved prediction, discrimination, and reclassification of CVD and CHD better than carotid ultrasound measures, although prediction and discrimination were similar for stroke/TIA.

Prevalence by Computed Tomographic Angiography of Coronary Plaques in South Asian and White Patients With Type 2 Diabetes Mellitus at Low and High Risk Using Four Cardiovascular Risk Scores (UKPDS, FRS, ASCVD, and JBS3).

The aim of this study was to explore the association between various cardiovascular (CV) risk scores and coronary atherosclerotic burden on coronary computed tomography angiography (CTA) in South Asians with type 2 diabetes mellitus and matched whites. Asymptomatic type 2 diabetic South Asians and whites were matched for age, gender, body mass index, hypertension, and hypercholesterolemia. Ten-year CV risk was estimated using different risk scores (United Kingdom Prospective Diabetes Study [UKPDS], Framingham Risk Score [FRS], AtheroSclerotic CardioVascular Disease [ASCVD], and Joint British Societies for the prevention of CVD [JBS3]) and categorized into low- and high-risk groups. The presence of coronary artery calcium (CAC) and obstructive coronary artery disease (CAD; ≥50% stenosis) was assessed using coronary CTA. Finally, the relation between coronary atherosclerosis on CTA and the low- and high-risk groups was compared. UKPDS, FRS, and ASCVD showed no differences in estimated CV risk between 159 South Asians and 159 matched whites. JBS3 showed a significant greater absolute CV risk in South Asians (18.4% vs 14.2%, p <0.01). Higher presence of CAC score >0 (69% vs 55%, p <0.05) and obstructive CAD (39% vs 27%, p <0.05) was observed in South Asians. South Asians categorized as high risk, using UKPDS, FRS, and ASCVD, showed more CAC and CAD compared than whites. JBS3 showed no differences. In conclusion, asymptomatic South Asians with type 2 diabetes mellitus more frequently showed CAC and obstructive CAD than matched whites in the population categorized as high-risk patients using UKPDS, FRS, and ASCVD as risk estimators. However, JBS3 seems to correlate best to CAC and CAD in both ethnicity groups compared with the other risk scores.

Coronary atherosclerotic plaque burden and composition by CT angiography in Caucasian and South Asian patients with stable chest pain.

AIMS: South Asian (SA) patients are known to have an increased incidence of acute cardiovascular events compared with Caucasians. The aim of this observational study was to compare the prevalence of coronary stenoses, the amount and composition of coronary atherosclerosis in a cohort of Caucasian and SA patients with stable chest pain, in non-acute settings. METHODS AND RESULTS: The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. In 963 consecutive Caucasian and SA patients undergoing coronary computed tomography angiography, atherosclerotic plaques were quantified using a semi-automated algorithm. The vessel per cent diameter and area stenosis were measured. Plaque composition was examined from the measurement of calcified, non-calcified, and total plaque burden. There were 420 Caucasian (238 males) and 543 SA (297 males) patients. Caucasian patients were older than SA patients (54.39 ± 11.65 vs. 49.83 ± 11.03 years) and had lower prevalence of diabetes (13.13 vs. 32.41%) and hyperlipidaemia (56.90 vs. 68.51%) (all P-values <0.001). After adjusting for differences in cardiovascular risk factors, there were no differences in per cent diameter and area stenosis, and no difference in the proportions of patients with one-, two-, or three-vessel disease. There was no difference in total plaque burden; however, the per cent non-calcified plaque composition was lower in Caucasians compared with SA (80.95 vs. 90.42%; P-value <0.001). CONCLUSION: This study conducted in non-acute settings showed an ethnic difference in composition of coronary atherosclerotic plaque with lower non-calcified composition in Caucasian patients compared with SA patients, which was independent of age, diabetes, hyperlipidaemia, and the other available cardiovascular risk factors.

Biomarkers of Key Biological Pathways in CVD.

This review provides background on the laboratory design for MESA (Multi-Ethnic Study of Atherosclerosis) as well as the approach used in MESA to select biomarkers for measurement. The research related to the multitude of circulating and urinary biomarkers of inflammation and other novel and emerging biological pathways in MESA is summarized by domain, or pathway, represented by the biomarker. The contributions of MESA biomarkers to our knowledge of these key pathways in the development and progression of atherosclerosis, cardiovascular disease, diabetes, kidney disease, and pulmonary disease are highlighted, as are the contributions of MESA to recommendations for clinical use of several of these biomarkers. In addition, contributions of MESA to multicohort genomics consortia and current collaborations in transomics and metabolomics are noted.

Bone Mineral Density and Progression of Subclinical Atherosclerosis in African-Americans With Type 2 Diabetes.

CONTEXT: Relative to European Americans, calcified atherosclerotic plaque (CP) is less prevalent and severe in African-Americans (AAs). OBJECTIVE: Predictors of progression of CP in the aorta, carotid, and coronary arteries were examined in AAs over a mean 5.3 ± 1.4-year interval. DESIGN: This is the African American-Diabetes Heart Study. SETTING: A type 2 diabetes (T2D)-affected cohort was included. PARTICIPANTS: A total of 300 unrelated AAs with T2D; 50% female, mean age 55 ± 9 years, baseline hemoglobin A1c 8.1 ± 1.8% was included. MAIN OUTCOME MEASURES: Glycemic control, renal parameters, vitamin D, and computed tomography-derived measures of adiposity, vascular CP, and volumetric bone mineral density (vBMD) in lumbar and thoracic vertebrae were obtained at baseline and follow-up. RESULTS: CP increased in incidence and quantity/mass in all three vascular beds over the 5-year study (P < .0001). Lower baseline lumbar and thoracic vBMD were associated with progression of abdominal aorta CP (P < .008), but not progression of carotid or coronary artery CP. Lower baseline estimated glomerular filtration rate was associated with progression of carotid artery CP (P = .0004), and higher baseline pericardial adipose volume was associated with progression of coronary artery (P = .001) and aorta (P = .0006) CP independent of body mass index. There was a trend for an inverse relationship between change in thoracic vBMD and change in aortic CP (P = .05). CONCLUSIONS: In this longitudinal study, lower baseline thoracic and lumbar vBMD and estimated glomerular filtration rate and higher pericardial adipose volumes were associated with increases in CP in AAs with T2D. Changes in these variables and baseline levels and/or changes in glycemic control, albuminuria, and vitamin D were not significantly associated with progression of CP.

Plasma FGF23 and Calcified Atherosclerotic Plaque in African Americans with Type 2 Diabetes Mellitus.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in disorders of serum phosphorus concentration and vitamin D. The role of FGF23 in vascular calcification remains controversial. METHODS: Relationships between FGF23 and coronary artery calcified atherosclerotic plaque (CAC), aortoiliac calcified plaque (CP), carotid artery CP, volumetric bone mineral density (vBMD), albuminuria, and estimated glomerular filtration rate (eGFR) were determined in 545 African Americans with type 2 diabetes (T2D) and preserved kidney function in African American-Diabetes Heart Study participants. Generalized linear models were fitted to test associations between FGF23 and cardiovascular, bone, and renal phenotypes, and change in measurements over time, adjusting for age, gender, African ancestry proportion, body mass index, diabetes duration, hemoglobin A1c, blood pressure, renin-angiotensin-system inhibitors, statins, calcium supplements, serum calcium, and serum phosphate. RESULTS: The sample was 56.7% female with a mean (SD) age of 55.6 (9.6) years, diabetes duration of 10.3 (8.2) years, eGFR 90.9 (22.1) ml/min/1.73 m2, urine albumin:creatinine ratio (UACR) 151 (588) (median 13) mg/g, plasma FGF23 161 (157) RU/ml, and CAC 637 (1,179) mg. In fully adjusted models, FGF23 was negatively associated with eGFR (p < 0.0001) and positively associated with UACR (p < 0.0001) and CAC (p = 0.0006), but not with carotid CP or aortic CP. Baseline FGF23 concentration did not associate with changes in vBMD or CAC after a mean of 5.1 years follow-up. CONCLUSIONS: Plasma FGF23 concentrations were independently associated with subclinical coronary artery disease, albuminuria, and kidney function in the understudied African American population with T2D. Findings support relationships between FGF23 and vascular calcification, but not between FGF23 and bone mineral density, in African Americans lacking advanced nephropathy.

Serum ferritin levels are associated with carotid atherosclerosis in Chinese postmenopausal women: the Shanghai Changfeng Study.

Postmenopausal women are at increased risk of CVD: the increased serum ferritin level may be involved in the pathogenesis. The aim of the present study is to investigate the relationship of ferritin and carotid atherosclerosis in postmenopausal women. A total of 1178 postmenopausal women (mean age, 60·8 years) were enrolled from the Changfeng Study. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral CIMT (carotid intima-media thickness) were measured using ultrasonography, and the presence of carotid plaques was assessed. Serum ferritin was measured using electrochemiluminescence immunoassay. The results showed that serum ferritin was 181·9 (sd 65·8) ng/ml in the postmenopausal women. Multivariate, linear, stepwise regression analysis demonstrated that age (standardised ß = 0·233, P< 0·001), alanine transaminase (standardised ß = 0·194, P< 0·001), log homeostasis model assessment index for insulin resistance (standardised ß = 0·181, P< 0·001), TAG (standardised ß = 0·083, P= 0·003), Hb (standardised ß = 0·080, P= 0·004) and PPG (2-h glucose levels following a 75-g oral glucose challenge) (standardised ß = 0·079, P= 0·004) were independently associated with serum ferritin. Compared with the ferritin level of subjects in the first quartile, that in the fourth quartile had greater CIMT, and higher prevalence of carotid plaque. After adjusting for conventional CVD risk factors, Hb, leucocytes, log urine albumin:creatinine ratio and liver function, the ferritin level of postmenopausal women in the fourth quartile had a 1·587-fold increased risk of carotid plaques relative to those in the lowest quartile. In conclusion, these results suggest that serum ferritin is independently and positively associated with carotid atherosclerosis in postmenopausal women and that ferritin may be implicated in atherosclerosis.

Variants on Chromosome 9p21 Confer Risks of Noncardioembolic Cerebral Infarction and Carotid Plaque in the Chinese Han Population.

AIMS: Considering that cerebral infarction (CI) may share a common etiological basis with coronary artery disease (CAD), we evaluated six CAD-related single-nucleotide polymorphisms (SNPs) on 9p21 for investigating the effect of 9p21 on CI or carotid plaque in the Chinese Han population. METHODS: Altogether, 528 patients with noncardioembolic CI (375 with carotid plaque and 153 without carotid plaque) and 258 control subjects were genotyped. Six SNPs previously shown to be associated with CAD were sequenced and assessed for association with CI and carotid plaque using odds ratio (OR) and 95% confidence interval (CI) from logistic regression models. RESULTS: The G allele frequencies of rs2383206 (OR=1.472, p=0.021) and rs4977574 (OR=1.519, p=0.013) significantly increased in patients with CI without carotid plaque compared with middle-aged patients in the control group. The CI risk was higher among the GG genotype carriers than among GA ＋ AA genotype carriers (OR=1.794, 95% CI=1.059-3.039, p=0.030 for rs2383206; OR=1.866, 95% CI=1.088-3.201, p=0.023 for rs4977574). In comparison with the non-GG genotype, the GG genotype of rs2383206 and rs4977574 combined had a 1.733-fold greater risk of CI in the middle-aged group. SNPs rs2383206 and rs4977574 were also associated with a risk of carotid plaque among patients with CI aged ＞ 65 years (OR=2.329, p=0.018 and OR=1.997, p=0.049, respectively). Moreover, six SNPs were strongly correlated with linkage disequilibrium. CONCLUSIONS: Genetic variations of rs2383206 and rs4977574 on 9p21 are potentially associated with CI and carotid plaque in the Chinese Han population. Our results provide further evidence that the 9p21 region represents a major risk locus for cerebrovascular diseases.

Predictors of carotid thickness and plaque progression during a decade: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND PURPOSE: Carotid artery intima-media thickness (IMT) and plaque are noninvasive markers of subclinical arterial injury that predict incident cardiovascular disease. We evaluated predictors of longitudinal changes in IMT and new plaque during a decade in a longitudinal multiethnic cohort. METHODS: Carotid IMT and plaque were evaluated in Multi-Ethnic Study of Atherosclerosis (MESA) participants at exams 1 and 5, a mean (standard deviation) of 9.4 (0.5) years later. Far wall carotid IMT was measured in both common and internal carotid arteries. A plaque score was calculated from all carotid segments. Mixed-effects longitudinal and multivariate regression models evaluated associations of baseline risk factors and time-updated medication use with IMT progression and plaque formation. RESULTS: The 3441 MESA participants were aged 60.3 (9.4) years (53% women; 26% blacks, 22% Hispanic, 13% Chinese); 1620 (47%) had carotid plaque. Mean common carotid artery IMT progression was 11.8 (12.8) µm/year, and 1923 (56%) subjects developed new plaque. IMT progressed more slowly in Chinese (ß=-2.89; P=0.001) and Hispanic participants (ß=-1.81; P=0.02), and with higher baseline high-density lipoprotein cholesterol (per 5 mg/dL; ß=-0.22; P=0.03), antihypertensive use (ß=-2.06; P=0.0004), and time on antihypertensive medications (years; ß=-0.29; P<0.0001). Traditional risk factors were associated with new plaque formation, with strong associations for cigarette use (odds ratio, 2.31; P<0.0001) and protection by black ethnicity (odds ratio, 0.68; P<0.0001). CONCLUSIONS: In a large, multiethnic cohort with a decade of follow-up, ethnicity was a strong, independent predictor of carotid IMT and plaque progression. Antihypertensive medication use was associated with less subclinical disease progression.

High-density lipoprotein subfractions and carotid plaque: the Northern Manhattan Study.

OBJECTIVE: The objective of this cross-sectional analysis was to investigate the relation between two major high-density lipoprotein cholesterol (HDL-C) subfractions (HDL2-C and HDL3-C) and carotid plaque in a population based cohort. METHODS: We evaluated 988 stroke-free participants (mean age 66 ± 8 years; 40% men; 66% Hispanic and 34% Non-Hispanic) with available data on HDL subfractions using precipitation method and carotid plaque area and thickness assessed by a high-resolution 2D ultrasound. The associations between HDL-C subfractions and plaque measurements were analyzed by quantile regression. RESULTS: Plaque was present in 56% of the study population. Among those with plaque, the mean ± SD plaque area was 19.40 ± 20.46 mm² and thickness 2.30 ± 4.45 mm. The mean ± SD total HDL-C was 46 ± 14 mg/dl, HDL2-C 14 ± 8 mg/dl, and HDL3-C 32 ± 8 mg/dl. After adjusting for demographics and vascular risk factors, there was an inverse association between HDL3-C and plaque area (per mg/dl: beta = -0.26 at the 75th percentile, p = 0.001 and beta = -0.32 at the 90th percentile, p = 0.02). A positive association was observed between HDL2-C and plaque thickness (per mg/dl; beta = 0.02 at the 90% percentile, p = 0.003). HDL-C was associated with plaque area (per mg/dl: beta = -0.18 at the 90th percentile, p = 0.01), but only among Hispanics. CONCLUSION: In our cohort we observed an inverse association between HDL3-C and plaque area and a positive association between HDL2-C and plaque thickness. HDL-C subfractions may have different contributions to the risk of vascular disease. More studies are needed to fully elucidate HDL-C anti-atherosclerotic functions in order to improve HDL-based treatments in prevention of vascular disease and stroke.

Carotid artery plaque morphology and composition in relation to incident cardiovascular events: the Multi-Ethnic Study of Atherosclerosis (MESA).

PURPOSE: To determine if carotid plaque morphology and composition with magnetic resonance (MR) imaging can be used to identify asymptomatic subjects at risk for cardiovascular events. MATERIALS AND METHODS: Institutional review boards at each site approved the study, and all sites were Health Insurance Portability and Accountability Act (HIPAA) compliant. A total of 946 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated with MR imaging and ultrasonography (US). MR imaging was used to define carotid plaque composition and remodeling index (wall area divided by the sum of wall area and lumen area), while US was used to assess carotid wall thickness. Incident cardiovascular events, including myocardial infarction, resuscitated cardiac arrest, angina, stroke, and death, were ascertained for an average of 5.5 years. Multivariable Cox proportional hazards models, C statistics, and net reclassification improvement (NRI) for event prediction were determined. RESULTS: Cardiovascular events occurred in 59 (6%) of participants. Carotid IMT as well as MR imaging remodeling index, lipid core, and calcium in the internal carotid artery were significant predictors of events in univariate analysis (P < .001 for all). For traditional risk factors, the C statistic for event prediction was 0.696. For MR imaging remodeling index and lipid core, the C statistic was 0.734 and the NRI was 7.4% and 15.8% for participants with and those without cardiovascular events, respectively (P = .02). The NRI for US IMT in addition to traditional risk factors was not significant. CONCLUSION: The identification of vulnerable plaque characteristics with MR imaging aids in cardiovascular disease prediction and improves the reclassification of baseline cardiovascular risk.