Ischemic stroke caused by large-artery atherosclerosis: a red flag for subclinical coronary artery disease.

Background: The coronary calcium score (CAC) measured on chest computerized tomography is a risk marker of cardiac events and mortality. We compared CAC scores in two multiethnic groups without symptomatic coronary artery disease: subjects in the chronic phase after stroke or transient ischemic attack and at least one symptomatic stenosis ≥50% in the carotid or vertebrobasilar territories (Groupathero) and a control group (Groupcontrol). Methods: In this cross-sectional study, Groupathero included two subgroups: GroupExtraorIntra, with stenoses in either cervical or intracranial arteries, and GroupExtra&Intra, with stenoses in at least one cervical and one intracranial artery. Groupcontrol had no history of prior stroke/transient ischemic attacks and no stenoses ≥50% in cervical or intracranial arteries. Age and sex were comparable in all groups. Frequencies of CAC ≥100 and CAC > 0 were compared between Groupathero and Groupcontrol, as well as between GroupExtraorIntr, GroupExtra&Intra, and Groupcontrol, with bivariate logistic regressions. Multivariate analyses were also performed. Results: A total of 120 patients were included: 80 in Groupathero and 40 in Groupcontrol. CAC >0 was significantly more frequent in Groupathero (85%) than Groupcontrol (OR, 4.19; 1.74-10.07; p = 0.001). Rates of CAC ≥100 were not significantly different between Groupathero and Groupcontrol but were significantly greater in GroupExtra&Intra (n = 13) when compared to Groupcontrol (OR 4.67; 1.21-18.04; p = 0.025). In multivariate-adjusted analyses, "Groupathero" and "GroupExtra&Intra" were significantly associated with CAC. Conclusion: The frequency of coronary calcification was higher in subjects with stroke caused by large-artery atherosclerosis than in controls.

Polygenic Risk Scores for Prediction of Subclinical Coronary Artery Disease in Persons With Human Immunodeficiency Virus (HIV): The Swiss HIV Cohort Study.

BACKGROUND: In people with human immunodeficiency virus (HIV) (PWH), individual polygenic risk scores (PRSs) are associated with coronary artery disease (CAD) events. Whether PRSs are associated with subclinical CAD is unknown. METHODS: In Swiss HIV Cohort Study participants of European descent, we defined subclinical CAD as presence of soft, mixed, or high-risk plaque (SMHRP) on coronary computed tomography (CT) angiography, or as participants in the top tertile of the study population's coronary artery calcium (CAC) score, using noncontrast CT. We obtained univariable and multivariable odds ratios (ORs) for subclinical CAD endpoints based on nongenetic risk factors, and validated genome-wide PRSs built from single nucleotide polymorphisms associated with CAD, carotid intima-media thickness (IMT), or longevity in the general population. RESULTS: We included 345 genotyped participants (median age, 53 years; 89% male; 96% suppressed HIV RNA); 172 and 127 participants had SMHRP and CAC, respectively. CAD-associated PRS and IMT-associated PRS were associated with SMHRP and CAC (all P < .01), but longevity PRS was not. Participants with unfavorable CAD-PRS (top quintile) had an adjusted SMHRP OR = 2.58 (95% confidence interval [CI], 1.18-5.67), and a CAC OR = 3.95 (95% CI, 1.45-10.77) vs. bottom quintile. Unfavorable nongenetic risk (top vs. bottom quintile) was associated with adjusted SMHRP OR = 24.01 (95% CI, 9.75-59.11), and a CAC-OR = 65.07 (95% CI, 18.48-229.15). Area under the receiver operating characteristic curve increased when we added CAD-PRS to nongenetic risk factors (SMHRP: 0.75 and 0.78, respectively; CAC: 0.80 and 0.83, respectively). CONCLUSIONS: In Swiss PWH, subclinical CAD is independently associated with an individual CAD-associated PRS. Combining nongenetic and genetic cardiovascular risk factors provided the most powerful subclinical CAD prediction.

Association between apnea-hypopnea index and coronary artery calcification: a systematic review and meta-analysis.

BACKGROUND: The present study aimed to evaluate the association between presence and severity of obstructive sleep apnoea (OSA) and the presence of subclinical coronary artery disease (CAD) as assessed by coronary calcium score. METHODS: Medline, Cochrane, and Google Scholar databases were searched. The presence of coronary artery calcification (CAC) and CAC score were assessed. RESULTS: Irrespective of the cut-off value of apnoea-hypopnea index (AHI) (5 or 15 events/h), patients in the OSA group had higher rate of CAC presence and mean CAC score than those in the control group. Subgroup analyses of patients monitored with home sleep apnoea testing (HSAT) or in-hospital/laboratory polysomnography showed that the OSA group had higher rate of CAC presence and mean CAC score than the control group, except in the comparison of mean CAC score between AHI ≥5 vs. <5 events/h for patients using HSAT, which was not significant. Pair-wise comparison showed that CAC score may increase with increased OSA severity. CONCLUSIONS: In participants without symptomatic coronary disease, the presence of OSA was associated with the presence and extent of CAC. However, potential confounders such as age, gender, and BMI and the diversity of CAC scores may affect the association.

Social Support and Subclinical Coronary Artery Disease in Middle-Aged Men and Women: Findings from the Pilot of Swedish CArdioPulmonary bioImage Study.

Social support has been associated with coronary artery disease (CAD), particularly in individuals who have sustained a cardiovascular event. This study investigated the relationship between social support and subclinical CAD among 1067 healthy middle-aged men and women. Social support was assessed with validated social integration and emotional attachment measures. Subclinical CAD was assessed as a coronary artery calcium score (CACS) using computed tomography. There was no association between social support and CACS in men. In women, low social support was strongly linked to cardiovascular risk factors, high levels of inflammatory markers, and CACS > 0. In a logistic regression model, after adjustment for 12 cardiovascular risk factors, the odds ratio (95% confidence intervals) for CACS > 0 in women with the lowest social integration, emotional attachment, and social support groups (reference: highest corresponding group) were 2.47 (1.23-5.12), 1.87 (0.93-3.59), and 4.28 (1.52-12.28), respectively. Using a machine learning approach (random forest), social integration was the fourth (out of 12) most important risk factor for CACS > 0 in women. Women with lower compared to higher or moderate social integration levels were about 14 years older in "vascular age". This study showed an association between lack of social support and subclinical CAD in middle-aged women, but not in men. Lack of social support may affect the atherosclerotic process and identify individuals vulnerable to CAD events.

Antiretroviral Drugs Associated With Subclinical Coronary Artery Disease in the Swiss Human Immunodeficiency Virus Cohort Study.

BACKGROUND: Coronary artery disease (CAD) events have been associated with certain antiretroviral therapy (ART) agents. In contrast, the influence of ART on subclinical atherosclerosis is not clear. The study objective was to assess the association between individual ART agents and the prevalence and extent of subclinical CAD. METHODS: Coronary artery calcium (CAC) scoring and coronary computed tomography angiography (CCTA) were performed in ≥45-year-old Swiss Human Immunodeficiency Virus Cohort Study participants. The following subclinical CAD endpoints were analyzed separately: CAC score >0, any plaque, calcified plaque, noncalcified/mixed plaque, segment involvement score (SIS), and segment severity score (SSS). Logistic regression models calculated by inverse probability of treatment weights (IPTW) were used to explore associations between subclinical CAD and cumulative exposure to the 10 most frequently used drugs. RESULTS: There were 403 patients who underwent CCTA. A CAC score >0 was recorded in 188 (47%), any plaque in 214 (53%), calcified plaque in 151 (38%), and noncalcified/mixed plaque in 150 (37%) participants. A CAC score >0 was negatively associated with efavirenz (IPTW adjusted odds ratio per 5 years 0.73, 95% confidence interval [CI] 0.56-0.96), tenofovir disoproxil fumarate (0.68, 95% CI 0.49-0.95), and lopinavir (0.64, 95% CI 0.43-0.96). Any plaque was negatively associated with tenofovir disoproxil fumarate (0.71, 95% CI 0.51-0.99). Calcified plaque was negatively associated with efavirenz (0.7, 95% CI 0.57-0.97). Noncalcified/mixed plaque was positively associated with abacavir (1.46, 95% CI 1.08-1.98) and negatively associated with emtricitabine (0.67, 95% CI 0.46-0.99). For SSS and SIS, we found no association with any drug. CONCLUSIONS: An increased risk of noncalcified/mixed plaque was only found in patients exposed to abacavir. Emtricitabine was negatively associated with noncalcified/mixed plaque, while tenofovir disoproxil fumarate and efavirenz were negatively associated with any plaque and calcified plaque, respectively.

Subclinical Atherosclerosis Imaging in People Living with HIV.

In many, but not all studies, people living with HIV (PLWH) have an increased risk of coronary artery disease (CAD) events compared to the general population. This has generated considerable interest in the early, non-invasive detection of asymptomatic (subclinical) atherosclerosis in PLWH. Ultrasound studies assessing carotid artery intima-media thickness (CIMT) have tended to show a somewhat greater thickness in HIV+ compared to HIV-, likely due to an increased prevalence of cardiovascular (CV) risk factors in PLWH. Coronary artery calcification (CAC) determination by non-contrast computed tomography (CT) seems promising to predict CV events but is limited to the detection of calcified plaque. Coronary CT angiography (CCTA) detects calcified and non-calcified plaque and predicts CAD better than either CAC or CIMT. A normal CCTA predicts survival free of CV events over a very long time-span. Research imaging techniques, including black-blood magnetic resonance imaging of the vessel wall and 18F-fluorodeoxyglucose positron emission tomography for the assessment of arterial inflammation have provided insights into the prevalence of HIV-vasculopathy and associated risk factors, but their clinical applicability remains limited. Therefore, CCTA currently appears as the most promising cardiac imaging modality in PLWH for the evaluation of suspected CAD, particularly in patients <50 years, in whom most atherosclerotic coronary lesions are non-calcified.

Impact of socioeconomic status on coronary artery calcification.

Background Low socioeconomic status is associated with an increased risk of coronary artery disease, but few studies have investigated the potential link between living in an area with a low versus a high socioeconomic status and coronary artery calcification, a marker of subclinical coronary artery disease. Design The design of this study was a cross-sectional study. Methods We evaluated 1067 participants with no history of coronary artery disease from the pilot phase of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Men and women aged 50-64 years were recruited from three high-socioeconomic status ( n = 541) and three low-socioeconomic status ( n = 526) areas in the city of Gothenburg (550,000 inhabitants). The coronary artery calcification score was assessed with the Agatston method using computed tomography, with individuals classified into either no coronary calcification ( n = 625; mean age, 57 years) or any coronary artery calcification ( n = 442; mean age, 59 years (men, 68.5%)). Results Coronary artery calcification was present in 244 (46.3%) and 198 (36.6%) individuals from the low- and high-socioeconomic status areas, respectively. Participants from the low-socioeconomic status areas had a significantly higher risk factor burden. In a multivariable logistic regression model with adjustment for age, sex and cardiovascular risk factors, the odds for coronary artery calcification were not significantly higher among persons living in low-socioeconomic status areas (odds ratio = 1.18, 95% confidence interval = 0.87-1.60). Conclusion In this relatively small cross-sectional study, we observed an association between living in a low-socioeconomic status area and coronary artery calcification. However, this was mostly explained by higher levels of cardiovascular disease risk factors, indicating that the effect of socioeconomic status on the atherosclerotic process works through an increased burden of cardiovascular disease risk factors.

High Calcium-Magnesium Ratio in Hair Is Associated with Coronary Artery Calcification in Middle-Aged and Elderly Individuals.

The interaction between calcium and magnesium as a risk modifier for cardiovascular disease (CVD) has been largely overlooked in previous studies, for the strict regulatory system in blood has been thought to keep such homeostatic interactions under tight control. This study aimed to investigate the association between calcium-magnesium ratio in hair and subclinical coronary artery calcification. Using multiple linear regression analysis, we examined the associations between calcium-magnesium ratio in hair and the coronary calcium score (CCS) in 216 Koreans aged 40 years and above (122 men and 94 women). We found that the calcium-to-magnesium ratio in hair was independently and positively associated with CCS after adjusting for age and sex (regression coefficient 6.051 ± 2.329, P = 0.010). When we assessed the association between the calcium-magnesium ratio and CCS after adjusting for potential cardiovascular risk factors and vascular function modifying drugs, we found that the strength of association with CCS was comparable to before (regression coefficient 5.434 ± 2.523, P = 0.032). Our findings suggest that among middle-aged and elderly Koreans without clinical CVD, the association between coronary artery calcification and hair calcium-magnesium ratio is stronger in those with a higher calcium-magnesium ratio in hair than in those with a lower ratio.

Trends in Coronary Atherosclerosis: A Tale of Two Population Subgroups.

BACKGROUND: We previously investigated trends in subclinical coronary artery disease and associated risk factors among autopsied non-elderly adults who died from nonnatural causes. Although grade of atherosclerosis declined from 1981 through 2009, the trend was nonlinear, ending in 1995, concurrent with increasing obesity/diabetes in this population. The previous study used linear regression and examined trends for all 4 major epicardial coronary arteries combined. The present investigation of coronary artery disease trends for the period 1995 through 2012 was prompted by a desire for more detailed examination of more recent coronary artery disease trends in light of reports that the epidemics of obesity and diabetes have slowed and are perhaps ending. METHODS: This population-based series of cross-sectional investigations identified all Olmsted County, Minnesota residents aged 16-64 years who died 1995 through 2012 (N = 2931). For decedents with nonnatural manner of death, pathology reports were reviewed for grade of atherosclerosis assigned each major epicardial coronary artery. Using logistic regression, we estimated calendar-year trends in grade (unadjusted and age- and sex-adjusted) for each artery, initially as an ordinal measure (range, 0-4); then, based on evidence of nonproportional odds, as a dichotomous variable (any atherosclerosis, yes/no) and as an ordinal measure for persons with atherosclerosis (range, 1-4). RESULTS: Of 474 nonnatural deaths, 453 (96%) were autopsied; 426 (90%) had coronary stenosis graded. In the ordinal-logistic model for trends in coronary artery disease grade (range, 0-4), the proportional odds assumption did not hold. In subsequent analysis as a dichotomous outcome (grades 0 vs 1-4), each artery exhibited a significant temporal decline in the proportion with any atherosclerosis. Conversely, for subjects with coronary artery disease grade 1-4, age- and sex-adjusted ordinal regression revealed no change over time in 2 arteries and statistically significant temporal increases in severity in 2 arteries. CONCLUSIONS: Findings suggest that efforts to prevent coronary artery disease onset have been relatively successful. However, statistically significant increases in the grade of atherosclerosis in 2 arteries among persons with coronary artery disease may be indicative of a major public health challenge.

Usefulness of coronary artery calcium for detecting significant coronary artery disease in asymptomatic individuals.

OBJECTIVES: To confirm the value of the coronary artery calcium (CAC) score as an indicator of significant coronary artery disease (CAD) in the asymptomatic Spanish population, using noninvasive coronary angiography by multidetector computed tomography (MDCT). METHODS: This was a retrospective study of 232 asymptomatic individuals, referred for a cardiovascular health checkup that included CAC and MDCT. RESULTS: Participants' mean age was 54.6 years (SD ± 12.8); 73.3% of them were men. The mean CAC value was 117.8 (SD ± 277). The individuals with arterial hypertension, diabetes mellitus, smoking and 3 or more risk factors had significantly greater CAC scores. Some 16.4% of the participants were in the ≥75 percentile population for CAC. The MDCT identified 148 individuals (63.8%) with CAD; the coronary lesions were not significant in 116 individuals (50%) and were significant (>50% stenosis) in 32 (13.8%). The participants with diabetes, smoking and ≥3 risk vascular factors had a greater prevalence of significant stenosis. The individuals with >50% stenosis had higher CAC values (352.5 vs. 1; P<.0001), and those in the ≥75 percentile had a high percentage of significant lesions (57.9% vs. 5.2%; P<.0001). The predictors of significant CAD were a CAC score >300 (OR=10.9; 95% CI 3.35-35.8; P=.0001), belonging to the ≥75 percentile (OR=5.65; 95% CI 1.78-17.93; P=.03) and having 3 or more vascular risk factors (OR=4.19; 95% CI 1.44-12.14; P=.008). CONCLUSION: CAC quantification is an effective method for determining the extent and magnitude of CAD and delimiting the predictive capacity of traditional risk factors.

Vitamin D deficiency is associated with development of subclinical coronary artery disease in HIV-infected African American cocaine users with low Framingham-defined cardiovascular risk.

UNLABELLED: Chronic cocaine use may lead to premature atherosclerosis, but the prevalence of and risk factors for coronary artery disease (CAD) in asymptomatic cocaine users have not been reported. The objective of this study was to examine whether vitamin D deficiency is associated with the development of CAD in human immunodeficiency virus (HIV)-infected African American cocaine users with low CAD risk. METHODS: In this prospective follow-up study, we investigated 169 HIV-infected African American cocaine users with low Framingham risk at baseline. The main outcome measures were incidence of subclinical CAD and development of subclinical CAD. RESULTS: Fifty of the 169 African Americans had evidence of subclinical disease on the initial cardiac computed tomography. A second cardiac computed tomography was performed on the 119 African Americans without disease on the first scan. The total sum of person-years of follow-up was 289.6. Subclinical CAD was detected in 11 of these, yielding an overall incidence of 3.80/100 person-years (95% confidence interval 1.90-6.80). Among the factors investigated, only vitamin D deficiency was independently associated with development of subclinical CAD. The study did not find significant associations between CD4 count, HIV viral load, or antiretroviral treatment use and the incidence of subclinical CAD. This study appears to suggest that there is a threshold level of vitamin D (10 ng/mL) above which the effect of vitamin D on subclinical CAD is diminished. CONCLUSION: The incidence of subclinical CAD in HIV-infected African American cocaine users with low CAD risk is high, especially in those with vitamin D deficiency. Well designed randomized clinical trials are warranted to confirm the role of vitamin D deficiency in the development of CAD in HIV-infected African American cocaine users with low CAD risk.