Associations Between Flavonoid Intake and Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Flavonoids may play a role in mitigating atherosclerotic cardiovascular diseases, with evidence suggesting effects may differ between vascular beds. Studies examining associations with subclinical markers of atherosclerosis between subpopulations with different underlying risks of atherosclerosis are lacking. METHODS: Among 5599 participants from the MESA (Multi-Ethnic Study of Atherosclerosis), associations between dietary flavonoid intakes (estimated from a food frequency questionnaire) and subclinical measures of atherosclerosis (ankle-brachial index, carotid plaques and intima-media thickness, and coronary artery calcification) were examined using repeated measures models. Exposures and outcomes were measured at exam 1 (2000-2002) and exam 5 (2010-2011). Stratified analyses and interaction terms were used to explore effect modification by time, sex, race/ethnicity, and smoking status. RESULTS: In the analytic population, at baseline, ≈46% were men with a median age of 62 (interquartile range, 53-70) years and total flavonoid intakes of 182 (interquartile range, 98-308) mg/d. After multivariable adjustments, participants with the highest (quartile 4) versus lowest (quartile 1) total flavonoid intakes had 26% lower odds of having an ankle-brachial index <1 (odds ratio, 0.74 [95% CI, 0.60-0.92]) and 18% lower odds of having a carotid plaque (odds ratio, 0.82 [95% CI, 0.69-0.99]), averaged over exams 1 and 5. Moderate (quartile 3) to high (quartile 4) intakes of flavonols, flavanol monomers, and anthocyanins were associated with 19% to 34% lower odds of having an ankle-brachial index <1 and 18% to 20% lower odds of having carotid plaque. Participants with the highest intakes of anthocyanins (quartile 4) at baseline had a marginally slower rate of carotid plaque progression than those with moderate intakes (quartiles 2 and 3). There were no significant associations with intima-media thickness or coronary artery calcification. Observed associations did not differ by sex, race/ethnicity, or smoking status. CONCLUSIONS: In this multi-ethnic population, higher dietary flavonoid intakes were associated with lower odds of peripheral and carotid artery atherosclerosis. Increasing intakes of healthy, flavonoid-rich foods may protect against atherosclerosis in the peripheral and carotid arteries.

Rare RNF213 variants is related to early-onset intracranial atherosclerosis: A Chinese community-based study.

BACKGROUND: The relationship between rare variants in Ring finger protein 213 (RNF213) and intracranial atherosclerosis (ICAS) remained unelucidated. Using whole-exome sequencing (WES) and high-resolution magnetic resonance imaging (HR-MRI), this study aimed at investigating the association between rare RNF213 variants and ICAS within a Chinese community-dwelling population. METHODS: The present study included 821 participants from Shunyi cohort. Genetic data of rare RNF213 variants were acquired by WES and were categorized by functional domains. Intracranial and extracranial atherosclerosis were assessed by brain HR-MRI and carotid ultrasound, respectively. Logistic regression and generalized linear regression were applied to evaluate the effects of rare RNF213 variants on atherosclerosis. Stratification by age were conducted with 50 years old set as the cutoff value. RESULTS: Ninety-five participants were identified as carriers of rare RNF213 variants. Carotid plaques were observed in 367 (44.7 %) participants, while ICAS was identified in 306 (37.3 %). Rare variants of RNF213 was not associated with ECAS. Employing HR-MRI, both the presence of rare variants (ß = 0.150, P = 0.025) and numerical count of variants (ß = 0.182, P = 0.003) were significantly correlated with ICAS within the group of age ≤50 years. Both variant existence (ß = 0.154, P = 0.014) and variant count (ß = 0.188, P = 0.003) were significantly associated with plaques in middle cerebral arteries within younger subgroup, rather than basilar arteries. Furthermore, a significant association was observed between variants that located outside the N-arm domain and ICAS in the younger subgroup (OR = 2.522, P = 0.030). Statistical results remained robust after adjusted for age, gender, and cardiovascular risk factors. CONCLUSIONS: Rare variants of RNF213 is associated with age-related ICAS in general Chinese population, highlighting the potential role of RNF213 as a genetic contributor to early-onset ICAS.

Carotid Ultrasound-Based Plaque Score for the Allocation of Aspirin for the Primary Prevention of Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis and the Atherosclerosis Risk in Communities Study.

BACKGROUND: Coronary artery calcium testing using noncontrast cardiac computed tomography is a guideline-indicated test to help refine eligibility for aspirin in primary prevention. However, access to cardiac computed tomography remains limited, with carotid ultrasound used much more often internationally. We sought to update the role of aspirin allocation in primary prevention as a function of subclinical carotid atherosclerosis. METHODS AND RESULTS: The study included 11 379 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) and ARIC (Atherosclerosis Risk in Communities) studies. A harmonized carotid plaque score (range, 0-6) was derived using the number of anatomic sites with plaque from the left and right common, bifurcation, and internal carotid artery on ultrasound. The 5-year number needed to treat and number needed to harm as a function of the carotid plaque score were calculated by applying a 12% relative risk reduction in atherosclerotic cardiovascular disease (ASCVD) events and 42% relative increase in major bleeding events related to aspirin use, respectively. The mean age was 57 years, 57% were women, 23% were Black, and the median 10-year ASCVD risk was 12.8%. The 5-year incidence rates (per 1000 person-years) were 5.5 (4.9-6.2) for ASCVD and 1.8 (1.5-2.2) for major bleeding events. The overall 5-year number needed to treat with aspirin was 306 but was 2-fold lower for individuals with carotid plaque versus those without carotid plaque (212 versus 448). The 5-year number needed to treat was less than the 5-year number needed to harm when the carotid plaque score was ≥2 for individuals with ASCVD risk 5% to 20%, whereas the presence of any carotid plaque demarcated a favorable risk-benefit for individuals with ASCVD risk >20%. CONCLUSIONS: Quantification of subclinical carotid atherosclerosis can help improve the allocation of aspirin therapy.

Systematic review and meta-analysis to assess the racial disparities in the outcomes of carotid endarterectomy in the United States.

OBJECTIVE: Race-based disparities in health care have been related to a myriad of prevailing factors among minorities in the United States. This study aims to study the race-based differences in the outcomes of carotid endarterectomy (CEA). METHODS: The PROSPERO database registered the review protocol (CRD42023428253). A systematic English literature review was performed using literature databases PubMed and Scopus from inception till June 2023. The review was designed on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and included studies reporting mortality, stroke, or composite outcome of mortality and stroke after CEA for carotid artery disease, regardless of any degree of stenosis including both symptomatic and asymptomatic patients. The risk of bias was evaluated utilizing the Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) tool. A pooled odds ratio (OR) for the overall mortality was computed, and a P value of < .05 was designated as statistically significant. Interstudy heterogeneity was evaluated by Q-metric and quantified using Higgins I2 statistics. RESULTS: Twelve studies were identified which included a total of 574,055 patients who underwent CEA from 1998 to 2022. Eleven of 12 studies reported 30-day mortality as an outcome for patients undergoing CEA in which 524,708 patients (92.5%) were White and 42,797 (7.5%) were non-White. The overall pooled OR indicated a statistical significance in 30-day mortality between White and non-White patients undergoing CEA (OR, 1.73; 95% confidence interval [CI], 1.37-2.18; P = .011) with substantial heterogeneity (I2 = 56.3%). Eleven of 12 studies reported stroke as an outcome for patients undergoing CEA in which 524,708 patients (92.5%) were White and 42,801 (7.5%) were non-White. The overall pooled OR indicated no statistical significance in stroke between White and non-White patients undergoing CEA (OR, 1.46; 95% CI, 1.28-1.65; P = .111) with moderate heterogeneity (I2 = 35.9%). Five of 12 studies reported composite mortality or stroke as an outcome for patients undergoing CEA. The overall pooled OR indicated no statistical significance in composite mortality or stroke between White and non-White patients undergoing CEA (OR, 1.40; 95% CI, 1.24-1.59; P = .467) with no heterogeneity (I2 = 0.0%). CONCLUSIONS: Non-White patients have a relatively higher risk of mortality; however, no significant difference was observed between the racial groups in terms of stroke or a composite outcome of mortality or stroke. The odds of mortality in non-White patients have been persistent throughout recent studies.

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.

The optimal WC cut-off points for the prediction of subclinical CVD as measured by carotid intima-media thickness among African adults: a cross-sectional study.

BACKGROUND: Increased waist circumference (WC) is one of the cardiovascular disease (CVD) risk factors used to predict cardiovascular events. Waist circumference cut-off values for predicting metabolic syndrome and other cardiovascular risks have been previously studied. Carotid intima-media thickness (CIMT) is one of the cardiovascular risk factor recently described and reported to be suitable as it is a direct measurement of vascular quality. Hence the aim of the present study was to determine the optimal WC cut-off point for the prediction of subclinical CVD. METHODS: The study was a cross-sectional study using quantitative methods, conducted among 1318 adults aged between 40 and 60 years old, residing in a rural Black population in Limpopo province. Carotid Intima-Media Thickness measurements were performed using a LOGIQ ultrasound system (GE Healthcare, CT, USA). Waist Circumference (WC) (cm) was measured to the nearest 0.1 cm. Bivariate correlation, logistic regression and receiver operating characteristic were analysed using the statistical package for social sciences version 26.0 software. RESULTS: Among the total population, 69% were women and 31% men with a mean age of 53 ± 7 years. Among women, WC at a cut-off value of 95 cm gave the highest sensitivity of 57%, the specificity of 55% and an area under the curve (AUC) of 0.588. In men, an optimum WC cut-off point of 82 cm yielded the highest sensitivity and specificity at 72% and 70% respectively, with an AUC of 0.767 p < 0.001. CONCLUSION: The traditional waist circumference cut-off points (94 cm for women and 80 cm for men) that are currently used for the diagnosis of metabolic syndrome might not be suitable in the prediction of an increased CIMT.

Plasma Sphingolipid Profile Associated With Subclinical Atherosclerosis and Clinical Disease Markers of Systemic Lupus Erythematosus: Potential Predictive Value.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects females more than males, with African Americans developing more severe manifestation of the disease. SLE patients are at increased risk for cardiovascular disease (CVD), and SLE women 35-44 years old have 50 fold the incidence rate of CVD. Because SLE patients do not follow the typical age and gender pattern for CVD, but instead an accelerated disease course, the traditional biomarkers of elevated LDL and total cholesterol levels do not accurately assess their CVD risk. Recently, we have reported that African American SLE patients had higher ceramide, hexosylceramide, sphingosine and dihydrosphingosine 1-phosphate levels compared to their healthy controls, and those with atherosclerosis had higher sphingomyelin and sphingoid bases levels than those without (PLoS One. 2019; e0224496). In the current study, we sought to identify sphingolipid species that correlate with and pose the potential to predict atherosclerosis severity in African American SLE patients. Plasma samples from a group of African American predominantly female SLE patients with well-defined carotid atherosclerotic plaque burden were analyzed for sphingolipidomics using targeted mass spectroscopy. The data demonstrated that at baseline, plaque area and C3 values correlated inversely with most lactoceramide species. After one-year follow-up visit, values of the change of plaque area correlated positively with the lactoceramide species. There was no correlation between LDL-C concentrations and lactoceramide species. Taken together, lactocylcermide levels may have a 'predictive' value and sphingolipidomics have an added benefit to currently available tools in early diagnosis and prognosis of African American SLE patients with CVD.

Baseline Characteristics of Patients with Symptomatic Carotid Webs: A Matched Case Control Study.

BACKGROUND AND PURPOSE: The baseline characteristics of patients with symptomatic carotid web (CaW) are unclear. We investigate demographic and cerebrovascular risk factors in patients with this overlooked stroke etiology. METHODS: We identified consecutive patients diagnosed with symptomatic CaW at a comprehensive stroke center from July 2014-December 2018. These patients were matched at a 1:4 ratio (based on age and NIHSS scores) to create a control group of acute ischemic stroke (AIS) patients with non-CaW etiologies from the local GetWithTheGuidelines stroke database. RESULTS: Thirty patients with symptomatic CaW were compared to 120 AIS patients with non-CaW etiologies. Symptomatic CaW patients were more likely to be female (73.3 vs. 44.2%; p = 0.004) and black (86.7 vs. 64.2%; p = 0.02). Symptomatic CaWs patients had a fewer absolute number of modifiable cerebrovascular risk factors (1.7±1.1 vs. 2.5±1.2; p = 0.002), lower rates of hypertension (43.4 vs. 63.3%; p = 0.04), and a more favorable lipid profile with lower average LDL (89.5±30.3 vs. 111.2±43.7 mg/dL; p = 0.01) and higher average HDL (47.9±11.3 vs. 42.2±13.8 mg/dL; p = 0.01) as compared to strokes with non-CaW etiology. Symptomatic CaW patients were more likely to have a large vessel occlusion (80.0 vs. 51.7%; p = 0.005), despite similar e-ASPECTS between the groups (8.1±2.1 vs. 8.3±2.2; p = 0.30). On multivariable analysis, symptomatic CaW was an independent predictor of independence at discharge (OR 3.72; 95%CI 1.27-10.94). CONCLUSION: A gender and racial predilection of symptomatic CaWs may exist as females and blacks were were found to be more likely affected. Symptomatic CaW patients have a more benign cerebrovascular risk factor profile corroborating the proposed mechanism of local stasis and thromboembolism. Despite presenting more commonly with LVO, symptomatic CaW was associated with good functional outcome, warranting further studies.

Nonclassical Monocytes (CD14dimCD16+) Are Associated With Carotid Intima-Media Thickness Progression for Men but Not Women: The Multi-Ethnic Study of Atherosclerosis-Brief Report.

[Figure: see text].

Association of "hypertriglyceridemic waist" with increased 5-year risk of subclinical atherosclerosis in a multi-ethnic population: a prospective cohort study.

BACKGROUND: Hypertriglyceridemic waist (HTGW), which incorporates measures of waist circumference and levels of triglyceride in blood, could act as an early-stage predictor to identify the individuals at high-risk for subclinical atherosclerosis. Previous studies have explored the cross-sectional association between HTGW and atherosclerosis; however, understanding how this association might change over time is necessary. This study will assess the association between HTGW with 5-year subclinical carotid atherosclerosis. METHODS: 517 participants of Aboriginal, Chinese, European, and South Asian ethnicities were examined for baseline HTGW and 5-year indices of subclinical atherosclerosis (intima media thickness (mm), total area (mm2), and plaque presence). Family history of cardiovascular disease, sociodemographic measures (age, sex, ethnicity, income level, maximum education), and traditional risk factors (systolic blood pressure, smoking status, total cholesterol, high-density lipoprotein cholesterol, body mass index) were incorporated into the models of association. These models used multiple linear regression and logistic regression. RESULTS: Baseline HTGW phenotype is a statistically significant and clinically meaningful predictor of 5-year intima media thickness (ß = 0.08 [0.04, 0.11], p < 0.001), total area (ß = 0.20 [0.07, 0.33], p = 0.002), and plaque presence (OR = 2.17 [1.13, 4.19], p = 0.02) compared to the non-HTGW group independent of sociodemographic factors and family history. However, this association is no longer significant after adjusting for the traditional risk factors of atherosclerosis (p = 0.27, p = 0.45, p = 0.66, respectively). Moreover, change in status of HTGW phenotype does not correlate with change in indices of atherosclerosis over 5 years. CONCLUSIONS: Our results suggest that when the traditional risk factors of atherosclerosis are known, HTGW may not offer additional value as a predictor of subclinical atherosclerosis progression over 5 years.

Race/Ethnicity, Cumulative Midlife Loss, and Carotid Atherosclerosis in Middle-Aged Women.

African-American women have elevated rates of cardiovascular disease compared with women of other races or ethnicities, and race/ethnicity-related stressors may play a role. We examined the association between a race/ethnicity-related stressor, midlife loss, and a marker of cardiovascular risk, carotid intima media thickness (IMT), in 1,410 African-American, White, Chinese, and Hispanic women from the Study of Women's Health Across the Nation. Participants were queried about losses annually over 12 years (1996-2013), with IMT assessed in year 12-13 via ultrasound. Linear regression models were used to examine associations between cumulative upsetting losses and IMT, adjusting for covariates. In minimally adjusted models in the full cohort, 3 or more upsetting losses (vs. none) were associated with IMT (ß = 0.03, 95% confidence interval (CI): 0.01, 0.05; P = 0.0003). Results were more robust among African-American women (ß = 0.042, 95% CI: 0.01, 0.07; P < 0.01) than White (ß = 0.014, 95% CI: -0.01, 0.03; P = 0.21), Chinese (ß = 0.036, 95% CI: -0.03, 0.10; P = 0.25), or Hispanic (ß = 0.036, 95% CI: -0.07, 0.14; P = 0.51) women, although associations among women from racial/ethnic minorities overall were of similar magnitude. Results persisted in fully adjusted models (P for interaction with race/ethnicity = 0.04). Midlife loss may be a pathway through which race/ethnicity influences cardiovascular risk for African-American women and, potentially, Chinese and Hispanic women.

Association of methylenetetrahydrofolate reductase (MTHFR) variant C677T and risk of carotid atherosclerosis: a cross-sectional analysis of 730 Chinese Han adults in Chongqing.

BACKGROUND: Uncertainty still remains on the correlation of methylenetetrahydrofolate reductase (MTHFR) variant C677T with risk of carotid atherosclerosis (CAS), and there is a lack of reports on C677T/MTHFR in the Asian population. The association of C677T/MTHFR polymorphisms with CAS in the Chinese Han population in Chongqing was investigated in the present study. METHODS: Subjects (n = 730, 214 females and 516 males, Han ethnicity) who provided an informed consent were randomly selected from the general population of Chongqing, China. Polymerase chain reaction-restriction fragment length polymorphism and Sanger sequencing genotyping assays were used to determine the MTHFR genotypes. The atherosclerosis index of the intima-media thickness (IMT) was measured by high-resolution ultrasound to evaluate the CAS. Less than 1.0 mm was considered as normal for IMT, 1.0-1.5 mm was considered as thickening, and ≥ 1.5 mm and a local bulge thickened in the lumen was considered as CAS. According to the carotid ultrasonography results, these subjects were divided into two groups: CAS-group (IMT ≥ 1.0 mm) and control group (IMT < 1.0 mm). RESULTS: The frequency of C/T heterozygotes, T/T homozygotes genotype was significantly higher in the subjects with CAS (62% vs. 36.9%; 16.2% vs. 9.5%; 47.2% vs. 27.9%, P < 0.05), while the frequency of C/C homozygotes and C allele was significantly lower (21.8% vs. 53.7%; 52.8% vs. 72.1%, P < 0.05), when compared to the control group. The risk of CAS was higher for subjects with C/T heterozygotes and T/T homozygotes (OR = 4.06, 95% CI: 2.76-5.98, P < 0.001 and OR = 3.14, 95% CI: 1.73-5.69, P < 0.001, respectively), when compared to the subjects with the C/C genotype. In the model 1 (CT + TT versus CC), C677T/MTHFR was significantly associated with the prevalence of CAS, and the all adjusted OR values for CAS were 3.87 (95% CI, 2.67 to 5.62) in all, 17.18 (95% CI, 7.27 to 40.49) in women and 2.57 (95% CI, 1.65 to 3.99) in men after adjusting for potential confounding factors. CONCLUSIONS: The present study suggests that a mutation in the methylenetetrahydrofolate reductase gene is a risk factor of CAS in the Chinese Han population.

Age-dependent effect of metabolic phenotypes on carotid atherosclerotic disease in coronary heart disease patients (CORDIOPREV study).

BACKGROUND: Aging is associated with a high risk for cardiovascular disease. The relation of obesity and risk of cardiovascular events appears to be more closely linked to certain clinical or metabolic phenotypes than to obesity itself. Our aim was to establish whether aging influenced the metabolic phenotypes regarding to cardiovascular risk, evaluated by changes in the intima media thickness-common carotid (IMT-CC), in coronary heart disease (CHD) patients. METHODS: In this cross-sectional study, 1002 CHD patients were studied at entry from the CORDIOPREV study. We performed carotid ultrasound assessment to obtain their IMT-CC values. Carotid atherosclerosis was considered to exist if IMT-CC > 0.7 mm. RESULTS: Age determined a higher IMT-CC, regardless metabolic phenotype (all p < 0.05). Metabolically healthy non-obese (MHNO) aged< 60 showed a lesser prevalence for carotid atherosclerotic disease than metabolically sick non-obese (MSNO) and obese (MSO), while MHNO aged≥60 only showed less prevalence for the disease than the MSO. Carotid atherosclerosis associated with age, sex, impaired fasting glucose (IFG), hypertension and high sensitivity C-reactive protein (hsCRP). However, in patients aged< 60, it associated with sex and IFG and in the age ≥ 60 group, with hypertension and hsCRP. CONCLUSIONS: Our results suggest that CHD patients aged≥60 are less metabolic flexible compared to patients aged< 60. Thus, MHO patients aged≥60 show the same risk of suffering carotid atherosclerosis as those with metabolic disease, while MHO patients aged< 60 show lower risk than MSO. This fact indicates the need to focus on therapeutic strategies in order to modify those parameters related to obesity and metabolic inflexibility in patients with CHD before entering old age.

The association between aortic arterial stiffness, carotid intima-media thickness and carotid plaques in community-dwelling older adults: A population-based study.

OBJECTIVE: Information on the associations among arterial stiffness, carotid intima-media thickness (cIMT) and carotid plaques as biomarkers of atherosclerosis is limited in diverse populations. We aimed to assess whether aortic pulse wave velocity (aPWV) - as a surrogate of arterial stiffness - is associated with increased cIMT and the presence of carotid plaques in a cohort of older adults of Amerindian ancestry. METHODS: Atahualpa residents aged ≥60 years (n = 320) underwent aPWV determinations, and carotid ultrasounds for cIMT and plaque assessment. Multivariate models were fitted to assess the independent association between the aPWV, and cIMT and carotid plaques, after adjusting for relevant confounders. Differences in risk factors across these biomarkers were investigated. RESULTS: Mean values of aPWV were 10.3 ± 1.8 m/s, and those of cIMT were 0.91 ± 0.21 mm (24% had a cIMT >1 mm). Carotid plaques were observed in 118 (37%) subjects. In univariate analyses, risk factors associated with an increased aPWV included age, female gender, poor physical activity and high blood pressure. An increased cIMT was associated with age, male gender, a poor diet, high blood pressure and severe tooth loss. The presence of carotid plaques was associated with increasing age, poor physical activity and high blood pressure. Multivariate models showed a significant association between aPWV and cIMT (ß: 0.028; 95% C.I.: 0.001-0.056; p = 0.047) but not between aPWV and carotid plaques (OR: 1.14; 95% C.I.: 0.83-1.56; p = 0.423). CONCLUSIONS: This study shows an independent association between aPWV and cIMT but not with carotid plaques. These biomarkers may indicate distinct phenotypes for atherosclerosis.

Morphological Carotid Plaque Area Is Associated With Glomerular Filtration Rate: A Study of South Asian Indian Patients With Diabetes and Chronic Kidney Disease.

We evaluated the association between automatically measured carotid total plaque area (TPA) and the estimated glomerular filtration rate (eGFR), a biomarker of chronic kidney disease (CKD). Automated average carotid intima-media thickness (cIMTave) and TPA measurements in carotid ultrasound (CUS) were performed using AtheroEdge (AtheroPoint). Pearson correlation coefficient (CC) was then computed between the TPA and eGFR for (1) males versus females, (2) diabetic versus nondiabetic patients, and (3) between the left and right carotid artery. Overall, 339 South Asian Indian patients with either type 2 diabetes mellitus (T2DM) or CKD, or hypertension (stage 1 or stage 2) were retrospectively analyzed by acquiring cIMTave and TPA measurements of their left and right common carotid arteries (CCA; total CUS: 678, mean age: 54.2 ± 9.8 years; 75.2% males; 93.5% with T2DM). The CC between TPA and eGFR for different scenarios were (1) for males and females -0.25 (P < .001) and -0.35 (P < .001), respectively; (2) for T2DM and non-T2DM -0.26 (P < .001) and -0.49 (P = .02), respectively, and (3) for left and right CCA -0.25 (P < .001) and -0.23 (P < .001), respectively. Automated TPA is an equally reliable biomarker compared with cIMTave for patients with CKD (with or without T2DM) with subclinical atherosclerosis.

Cardiovascular Disease Risk Factor Burden During the Menopause Transition and Late Midlife Subclinical Vascular Disease: Does Race/Ethnicity Matter?

Background The extent to which cardiovascular disease (CVD) risk factors across the menopause explain racial/ethnic differences in subclinical vascular disease in late midlife women is not well documented and was explored in a multi-ethnic cohort. Methods and Results Participants (n=1357; mean age 60 years) free of clinical CVD from the Study of Women's Health Across the Nation had common carotid artery intima-media thickness, interadventitial diameter, and carotid plaque presence assessed by ultrasonography on average 13.7 years after baseline visit. Early to late midlife time-averaged cumulative burden of traditional CVD risk factors calculated using serial measures from baseline to the ultrasound visit were generally less favorable in black and Hispanic women compared with white and Chinese women, including education and smoking status and time-averaged cumulative blood pressure, high-density lipoprotein cholesterol, and fasting insulin. Independent of these risk factors, BMI, and medications, common carotid artery intima-media thickness was thicker in black women, interadventitial diameter was wider in Chinese women, yet plaque presence was lower in black and Hispanic women compared with white women. CVD risk factor associations with subclinical vascular measures did not vary by race/ethnicity except for high-density lipoprotein cholesterol on common carotid artery intima-media thickness; an inverse association between high-density lipoprotein cholesterol and common carotid artery intima-media thickness was observed in Chinese and Hispanic but not in white or black women. Conclusions Race/ethnicity did not particularly moderate the association between traditional CVD risk factors measured across the menopause transition and late midlife subclinical vascular disease. Unmeasured socioeconomic, cultural, and nontraditional biological risk factors likely play a role in racial/ethnic differences in vascular health and merit further exploration.

Alcohol consumption and subclinical atherosclerosis among South Asians: Findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study.

BACKGROUND: South Asians are the second fastest growing ethnic group in the United States, and they have a high risk for cardiovascular disease (CVD). Moderate alcohol consumption has been associated with lower CVD risk in some race/ethnic groups, but the association of alcohol consumption and atherosclerosis in South Asians has not been investigated. METHODS AND RESULTS: We used data from 906 South Asian participants who participated in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort (2010-2012). Alcohol consumption was ascertained via questionnaire, coronary artery calcium (CAC) was measured with computed tomography, and common carotid artery intima-media thickness (cIMT) was measured using B-mode ultrasonography. We used multivariable regression models to examine cross-sectional associations of alcohol consumption with the presence and amount of CAC and cIMT. Compared with never drinkers, participants consuming 4-7 drinks/week had a 63% decreased odds of any CAC after adjusting for potential confounders and mediators. Participants consuming 4-7 drinks/week had significantly lower odds of CAC score between 1 and 300 [OR (95% CI): 0.34 (0.16-0.72)]. A similar inverse association was seen for the odds of CAC>300 [OR (95% CI): 0.28 (0.07-0.97)]. Alcohol consumption of >7 drinks/week was associated with a 0.096 mm increase in common-cIMT. CONCLUSION: There was an inverse association between the amount of alcohol intake and CAC among South Asians while a positive association was found between alcohol consumption and common-cIMT. Long-term follow-up of the MASALA cohort will examine prospective associations of alcohol intake with the progression of subclinical atherosclerosis, incident CVD events, and mortality.

Complex contaminant mixtures and their associations with intima-media thickness.

BACKGROUND: The burden of cardiovascular disease (CVD) morbidity and mortality is higher among Indigenous persons, who also experience greater health disparities when compared to non-Indigenous Canadians, particularly in remote regions of Canada. Assessment of carotid intima-media thickness (cIMT), a noninvasive screening tool and can be used as biomarker to assess increased CVD risk. Few studies have examined environmental contaminant body burden and its association with cIMT. METHODS: Data from the Environment-and-Health Study in the Eeyou Istchee territory of northern Québec, Canada was used to assess complex body burden mixtures of POPs, metals and metalloids among (n = 535) Indigenous people between 15 and 87 years of age with cIMT. First, Principal Component Analysis (PCA) was used to reduce the complexity of the contaminant data. Second, based on the underlying PCA profiles from the biological data, we examined each of the prominent principal component (PC) axes on cIMT using multivariable linear regression models. Lastly, based on these PC axes, cIMT was also regressed on summed (Σ) organic compound concentrations, polychlorinated biphenyl, perfluorinated compounds, respectively, ∑10 OCs, ∑13 PCBs, ∑3PFCs, and nickel. RESULTS: Most organochlorines and PFCs loaded primarily on PC-1 (53% variation). Nickel, selenium, and cadmium were found to load on PC-5. Carotid-IMT was significantly associated with PC-1 ß = 0.004 (95 % CI 0.001, 0.007), and PC-5 ß = 0.013 (95 % CI 0.002, 0.023). However, the association appears to be greater for PC-5, accounting for 3% of the variation, and mostly represented by nickel. Results show that that both nickel, and ∑3PFCs were similarly associated with cIMT ß = 0.001 (95 % CI 0.0003, 0.003), and ß = 0.001 (95 % CI 0.0004, 0.002), respectively. But ∑10OCs was significantly associated with a slightly greater ß = 0.004 (95 % CI 0.001, 0.007) cIMT change, though with less precision. Lastly, ∑13PCBs also increased ß = 0.002 (95 % CI 0.0004, 0.003) cIMT after fully adjusting for covariates. CONCLUSION: Our results suggest that environmental contaminants are associated with cIMT. This is important for the Cree from the Eeyou Istchee territory who may experience higher body burdens of contaminants than non-Indigenous Canadians.

[Prevalence and influencing factors of carotid plaque in population at high-risk for cardiovascular disease in Jiangsu province].

Objective: To understand the prevalence of carotid plaque (CP) in population at high-risk for cardiovascular disease (CVD) in Jiangsu province and identify related influencing factors. Methods: Based on the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project from 2015 to 2016, a total of 11 392 persons at high-risk for CVD were selected from six project areas in Jiangsu province for the questionnaire survey, physical measurement, laboratory test and bilateral ultrasound examination of carotid arteries. The prevalence of CP and influencing factors of abnormal carotid arteries, CP and plaque burden (CP≥2) were analyzed. Results: Among the persons surveyed, 4 821 (42.3%) were males. The age of the persons surveyed was (59.4±8.9) years. There were 5 971 abnormal carotid arteries cases (52.4%), including 1 782 carotid intima-media thickness thickening cases (15.6%), 3 811 CP cases (33.5%) and 378 carotid stenosis cases (3.3%). Older age (OR=2.253, 95%CI: 2.127-2.386), urban residence (OR=2.622, 95%CI: 2.375-2.895), hypertension (OR=1.439, 95%CI: 1.195-1.732), smoking (OR=1.441, 95%CI: 1.259- 1.650), pulse pressure difference (OR=1.270, 95%CI: 1.198-1.347), fasting plasma glucose (FPG) (OR=1.109, 95%CI: 1.059-1.161) and LDL-C/HDL-C (OR=1.225, 95%CI: 1.164-1.288) were possible risk factors of CP in population at high risk for CVD. Being women (OR=0.558, 95%CI: 0.494-0.630), high BMI (OR=0.948, 95%CI: 0.904-0.994), higher levels of education (OR=0.708, 95%CI: 0.531-0.945), and higher annual household income (OR=0.773, 95%CI: 0.669-0.894) were the possible protective factors. Conclusions: Over half of the population at high-risk for CVD in Jiangsu showed abnormal carotid arteries. High blood pressure, high blood glucose, high blood lipids and smoking were the main factors that could be changed.

Carotid Intima-Media Thickness and Carotid Plaque: A Pilot Study of Risk Factors in an Indigenous Nigerian Population.

BACKGROUND: Risk factors for carotid intima-media thickness (cIMT) and carotid plaque (CP) differ by ethnicity; however, this is not well understood in some ethnic populations. This work examines the risk factors for cIMT and CP in an indigenous Nigerian population. METHODS: We assessed cIMT and CP in 122 participants and then performed biochemical analysis: fasting blood glucose (FBG), hemoglobin A1c, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and total cholesterol (TC). The clinical history and anthropometric characteristics of participants were recorded. Linear models were used to assess the factors associated with cIMT and CP, and stepwise multivariate regression analyses were conducted to assess the predictors of cIMT and CP. RESULTS: The cIMT thickness varied from .5 mm to 1.3 mm. Family history of heart disease (FHHDx), physical activity, FBG, HDL-C, TG, TC, body mass index (BMI), systolic pressure, and waist circumference were significantly associated with cIMT (P ≤ .01). High systolic (ß = .008) and diastolic (ß = .17) pressure, FHHDx (ß = .24), age (ß = .004), physical activity (ß = -.09), and waist circumference (ß = -.017) significantly predicted 85% of the variation in cIMT (P < .001 for all). Family history of hypertension (FHH), LDL-C, and high blood pressure were significantly associated with CP (P ≤ .05). The significant predictors of CP were FHH (ß = .145, P = .03), smoking (ß = .167, P = .01), HDL-C (ß = .283, P < .001), weight (ß = .150, P = .04), and BMI (ß = .183, P = .01), explaining most of the 43.2% variation in CP. CONCLUSIONS: Some of the risk factors differ from those of other ethnicities, suggesting a need for population-specific approach to risk assessment and early detection of subclinical disease.