Low testosterone (T) is associated with cardiovascular disease (CVD) and increased mortality in the general population; however, the impact of T on subclinical CVD in HIV disease is unknown. This study examined the relationships among free testosterone (FT), subclinical CVD, and HIV disease.
This was a cross-sectional analysis in 322 HIV-uninfected and 534 HIV-infected men in the Multicenter AIDS Cohort Study. Main outcomes were coronary artery calcification presence, defined as a coronary artery calcium (CAC) score > 10 (CAC score was the geometric mean of the Agatston scores of two computed tomography replicates), and far wall common carotid intima-media thickness (IMT)/carotid lesion presence by B-mode ultrasound.
Compared with the HIV-uninfected men in our sample, HIV-infected men were younger, with lower body mass index (BMI) and more often Black. HIV-infected men had lower FT (age-adjusted FT 88.7 ng/dL vs. 101.7 ng/dL in HIV-uninfected men; P = 0.0004); however, FT was not associated with CAC, log carotid IMT, or the presence of carotid lesions. HIV status was not associated with CAC presence or log carotid IMT, but was associated with carotid lesion presence (adjusted odds ratio 1.69; 95% confidence interval 1.06, 2.71) in HIV-infected men compared with HIV-uninfected men.
Compared with HIV-uninfected men, HIV-infected men had lower FT, as well as more prevalent carotid lesions. In both groups, FT was not associated with CAC presence, log carotid IMT, or carotid lesion presence, suggesting that FT does not influence subclinical CVD in this population of men with and at risk for HIV infection.
cardiovascular disease; HIV; testosterone
Coronary artery calcium (CAC) and carotid intima-media thickness (IMT) are noninvasive measures of atherosclerosis that consensus panels have recommended as possible additions to risk factor assessment for predicting the probability of cardiovascular disease (CVD) occurrence.
To assess whether maximum carotid IMT or CAC (Agatston Score) is the better predictor of incident CVD.
Design, Setting, Patients
Prospective cohort study of 45–84 year-olds initially free of CVD (n = 6,698) in four ethnic groups, with standardized carotid IMT and CAC measures at baseline, in six field centers of the Multi-Ethnic Study of Atherosclerosis (MESA).
Main Outcome Measure(s)
Incident CVD events (coronary heart disease, stroke, and fatal CVD) over a maximum of 5.3 years of follow-up.
There were 222 CVD events during follow-up. CAC was associated more strongly than carotid IMT with risk of incident CVD. After adjustment for each other and traditional CVD risk factors, the hazard of CVD increased 2.1-fold (95% CI 1.8–2.5) for each standard deviation greater level of log-transformed CAC, versus 1.3-fold (95% CI 1.1–1.4) for each standard deviation greater maximum IMT. For coronary heart disease, the hazard ratios per standard deviation increment were 2.5-fold (95% CI 2.1–3.1) for CAC and 1.2-fold (95% CI 1.0–1.4) for IMT. An ROC analysis also suggested that CAC predicted incident CVD better than IMT did.
Although whether and how to clinically use bio-imaging tests of subclinical atherosclerosis remains a topic of debate, this study found that CAC predicts subsequent CVD events better than does carotid IMT.
Circulating adiponectin has been associated with both clinical and subclinical cardiovascular disease (CVD). Variants of the adiponectin gene (ADIPOQ) are associated with clinical CVD, but little is known about associations with subclinical CVD. We studied the association of 11 ADIPOQ SNPs with common and internal carotid intima media thickness (cIMT), presence of coronary artery calcification (CAC), and CAC scores (in those with CAC) in 2847 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were Caucasian (n=712), African-American (n=712), Chinese (n=718), and Hispanic (n=705). All models were adjusted for age, sex, and field site, and stratified by race/ethnic group. African-Americans with genotypes AG/GG of rs2241767 had 36% greater (95% CI (16%, 59%), p=0.0001) CAC prevalence; they also had a larger common cIMT (p=0.0043). Also in African-Americans, genotypes AG/AA of rs1063537 were associated with a 35% (95% CI (14%, 59%), p=0.0005) greater CAC prevalence. Hispanics with the AA genotype of rs11711353 had a 37% (95% CI (14%, 66%), p=0.0011), greater CAC prevalence compared to those with the GG genotype. Additional adjustment for ancestry in African-American and Hispanic participants did not change the results. No single SNP was associated with subclinical CVD phenotypes in Chinese or Caucasian participants. There appears to be an association between ADIPOQ SNPs and subclinical CVD in African-American and Hispanics. Replication as well as assessment of other ADIPOQ SNPs appears warranted.
To determine the association of fetuin-A with subclinical CVD in community-living individuals.
Fetuin-A is a hepatic secretory protein that inhibits arterial calcium deposition in vitro. Lower fetuin-A levels are associated with arterial calcification and death in end-stage renal disease populations. The association of fetuin-A with subclinical cardiovascular disease (CVD) in the general population is unknown.
Among 1,375 community-living individuals without prevalent clinical CVD, we measured plasma fetuin-A concentrations measured by ELISA. Peripheral arterial disease (PAD) was defined by ankle brachial index (ABI) < 0.90, coronary artery calcification (CAC) was measured by computed tomography, and common and internal intima media thickness (cIMT) were measured by carotid ultrasound. PAD was measured concurrent with fetuin-A, and CAC and cIMT was measured 4.6 years (mean) later.
Mean age was 70 ± 11 years and 64% were female. Fetuin-A levels were inversely associated with CAC severity. When evaluated as CAC categories (0, 1–100, 101–300, > 300) using ordinal logistic regression, each standard deviation higher fetuin-A was associated with a 31% lower odds of CAC severity (proportional odds ratio [POR] 0.69; 95% confidence interval [CI] 0.46, 0.92; p=0.008) in models adjusted for demographics, lifestyle factors, traditional CVD risk factors and kidney function. In contrast, no association of fetuin-A was observed with PAD or high common or internal cIMT in adjusted models.
Lower fetuin-A levels are independently associated with greater CAC severity, but not PAD or cIMT. If confirmed, fetuin-A may mark calcium deposition within the vasculature, but not atherosclerosis per se.
Fetuin-A; Cardiovascular Disease; Coronary Artery Calcification
Elevated plasma fibrinogen is a prothrombotic risk factor for cardiovascular disease (CVD). Recent small studies report that fibrinogen oxidative modifications, specifically tyrosine residue nitration, can occur in inflammatory states and may modify fibrinogen function. HDL cholesterol is inversely related to CVD and suggested to reduce the oxidation of LDL cholesterol, but whether these antioxidant functions extend to fibrinogen modifications is unknown. We used a recently validated ELISA to quantify nitrated fibrinogen during experimental human endotoxemia (N=23) and in a cohort of healthy adults (N=361) who were characterized for inflammatory and HDL parameters as well as subclinical atherosclerosis measures, carotid artery intima-medial thickness (IMT) and coronary artery calcification (CAC). Fibrinogen nitration increased following endotoxemia and directly correlated with accelerated ex vivo plasma clotting velocity. In the observational cohort, nitrated fibrinogen was associated with levels of CRP and serum amyloid A. Nitrated fibrinogen levels were not lower with increasing HDL cholesterol and did not associate with IMT and CAC. In humans, fibrinogen nitration was induced during inflammation and was correlated with markers of inflammation and clotting function but not HDL cholesterol or subclinical atherosclerosis in our modest sample. Inflammation-induced fibrinogen nitration may be a risk factor for promoting CVD events.
Fibrinogen; Nitration; Intima-medial thickness; Coronary artery calcification; High-density lipoprotein (HDL)
Racial differences are known to account for a higher incidence of systemic lupus erythematosus (SLE), as well as increased disease severity and mortality. The purpose of this study was to determine if there are any race-specific risk factors that affect measures of subclinical atherosclerosis in SLE patients.
Traditional and SLE-related cardiovascular disease (CVD) risk factors were assessed in 106 female SLE patients. Carotid medial intimal medial thickness (mIMT) and coronary artery calcification (CAC) were measured on all subjects. Differences were evaluated between races for all clinical, serologic, and CVD risk factors and the racial interactions with all covariables. Outcomes included mIMT and CAC.
There were no significant differences between races with regard to mIMT or CAC. Significant covariables in the final model for mIMT included age, triglycerides, glucose, and race-age and race-smoking interactions. A prediction model with fixed significant covariables demonstrated that Black subjects with a smoking history had a significantly higher mIMT than Blacks who had never smoked, an effect not seen in Whites. There were no differences between having CAC or with the CAC scores between the races. In the final model for CAC, age and SLE disease duration were significant covariables impacting CAC.
When controlling for other significant CVD covariables and interactions, Black women, but not White, with SLE with a history of smoking have higher mIMT measurements than those who have never smoked. This is the first report documenting the race-specific effect of smoking on subclinical measures of CVD in SLE.
lupus; cardiovascular; smoking; race
Racial differences exist in disease rates and mortality in both cardiovascular disease (CVD) and Systemic Lupus Erythematosus (SLE). The objective of this cross-sectional study was to compare the frequency of and risk factors for subclinical CVD in African-American (AA) and Caucasian women with SLE and no prior CVD events.
Traditional CVD risk factors and SLE-related factors were assessed in 309 SLE women. Subclinical CVD was assessed by carotid ultrasound to measure intima-medial thickness (IMT) and plaque, and electron beam computed tomography (EBCT) to measure coronary artery calcium (CAC).
AA had less education, higher body mass index, blood pressure, lipoprotein(a), CRP, fibrinogen, and ESR, but lower albumin; more and longer duration of corticosteroid use; higher SLE disease activity and damage; and more had dsDNA antibodies compared to Caucasian women, after adjustment for age and study-site. More AA had carotid plaque (adjusted OR 1.94, 95%CI 1.03, 3.65) and higher carotid IMT (0.620 vs. 0.605mm, p=0.07) compared with Caucasians, but similar CAC. Multivariate analysis included risk factor variables significantly different between the racial groups and associated with plaque: blood pressure, current corticosteroid use, SLE disease activity and damage. All factors contributed, but no individual risk factor fully accounted for the association between race and plaque.
In conclusion, the presence of carotid plaque was higher in AA compared with Caucasian women with SLE, in contrast to studies of non-SLE subjects, where AA have similar or less plaque than Caucasians. A combination of SLE-related and traditional CVD risk factors explained the racial difference in plaque burden.
Systemic Lupus Erythematosus; Race; Cardiovascular Disease
Recent studies indicate that subclavian stenosis (SS), diagnosed by a large systolic blood pressure difference (SBPD) between the right and left brachial arteries, is associated with cardiovascular disease (CVD) risk factors and outcomes. We sought to describe the epidemiology of SS and determine its association with markers of subclinical CVD in the baseline cohort of the Multi-Ethnic Study of Atherosclerosis.
We defined SS by an absolute SBPD ≥15 mmHg. Peripheral artery disease (PAD) was defined by an ankle-brachial index ≤0.90. The coronary artery calcium score (CAC) and the common-carotid artery intima-media thickness (CCA-IMT) were measured by computed tomography and B-mode ultrasound, respectively. Odds ratios for the associations of SS with risk factors and subclinical disease were estimated using logistic regression.
Of 6,743 subjects studied, 307 participants (4.6%) had SS, with a higher prevalence in women (5.1%) than men (3.9%), and in African-Americans (7.4%) and non-Hispanic whites (5.1%) than Hispanic (1.9%) or Chinese (1.0%) participants (p<0.01). In a model including age, gender, ethnicity, traditional and novel CVD risk factors, significant associations with SS were observed for C-reactive protein (highest vs. three lower quartiles: OR=1.41; 95%CI: 1.06-1.87) and brachial artery pulse pressure (OR=1.12 /10 mmHg; 95%CI: 1.03-1.21). Adjusted for age, gender, ethnicity, traditional and novel CVD risk factors, SS was significantly associated with PAD (OR=2.35; 1.55-3.56), with CCA-IMT (highest vs. the lower three quartiles: OR=1.32; 1.00-1.75), and high CAC (score >100 vs. score=0; OR=1.43; 1.03-2.01).
The subclavian stenosis is positively associated with other markers of subclinical atherosclerosis.
subclavian artery; blood pressure; atherosclerosis; epidemiology
Determine the association of coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood with the presence and progression of coronary artery calcified (CAC) plaque and carotid intima-media thickness (cIMT) later in life.
Methods and Results
CARDIA is a cohort of 5115 white and black adults who were 18–30 years when they completed a baseline clinic examination in 1985–1986. Subsequent examinations were conducted 2, 5, 7, 10, 15, and 20 years later. After multivariable adjustment, no association was observed between average coffee, decaffeinated coffee, or caffeine consumption (years 0 and 7) and presence of CAC [score >0 Agatston units (AU) at year 15 or 20], CAC progression (incident CAC at year 20 or an increase in CAC score ≥20 AU), or high cIMT (>80th percentile, year 20). Tea consumption, however, displayed a non-significant trend for an inverse association with CAC (ptrend0.08) and an inverse association with CAC progression (ptrend0.04), but no association with high cIMT (ptrend>0.2). Stratification of the coffee analyses by sex, race, or smoking yielded similar non-significant patterns.
We observed no substantial association between coffee or caffeine intake and coronary and carotid atherosclerosis. However, our results suggested an inverse association between tea and CAC, but not carotid atherosclerosis.
antioxidants; atherosclerosis; carotid arteries; diet; epidemiology; nutrition
The association between diet and cardiovascular disease (CVD) may be mediated partly through inflammatory processes and reflected by markers of subclinical atherosclerosis.
We investigated whether empirically derived dietary patterns are associated with coronary artery calcium (CAC) and common and internal carotid artery intima media thickness (IMT) and whether prior information about inflammatory processes would increase the strength of the associations.
At baseline, dietary patterns were derived with the use of a food-frequency questionnaire, and inflammatory biomarkers, CAC, and IMT were measured in 5089 participants aged 45–84 y, who had no clinical CVD or diabetes, in the Multi-Ethnic Study of Atherosclerosis. Dietary patterns based on variations in C-reactive protein, interleukin-6, homocysteine, and fibrinogen concentrations were created with reduced rank regression (RRR). Dietary patterns based on variations in food group intake were created with principal components analysis (PCA).
The primary RRR(RRR 1) and PCA(PCA factor 1) dietary patterns were high in total and saturated fat and low in fiber and micronutrients. However, the food sources of these nutrients differed between the dietary patterns. RRR 1 was positively associated with CAC [Agatston score >0: OR(95% CI) for quartile 5 compared with quartile 1 = 1.34 (1.05, 1.71); ln(Agatston score = 1): P for trend = 0.023] and with common carotid IMT [≥1.0 mm: OR (95% CI) for quartile 5 compared with quartile 1 = 1.33 (0.99, 1.79); ln(common carotid IMT): P for trend = 0.006]. PCA 1 was not associated with CAC or IMT.
The results suggest that subtle differences in dietary pattern composition, realized by incorporating measures of inflammatory processes, affect associations with markers of subclinical atherosclerosis.
Dietary patterns; principal components analysis; reduced rank regression; carotid artery intima media thickness; coronary artery calcium
Despite the significant morbidity and mortality attributable to cardiovascular disease (CVD), risk stratification remains an important challenge in the chronic kidney disease(CKD) population. We examined the discriminative ability of non-invasive measures of atherosclerosis, including carotid intima-media thickness(cIMT), carotid plaque, coronary artery calcification(CAC) and ascending and descending thoracic aorta calcification(TCAC), and Framingham Risk Score (FRS) to predict self-reported prevalent CVD.
Methods and Results
Participants were enrolled in the cIMT ancillary study of the Chronic Renal Insufficiency Cohort(CRIC) Study and also had all of the above measures within an 18 month period. CVD was present in 21% of study participants. C-statistics were used to ascertain the discriminatory power of each measure of atherosclerosis. The study population (n=220) was 64% male; 51% black and 45% white. The proportion of individuals with estimated glomerular filtration rate ≥60, 45–59, 30–44, and <30ml/min/1.73m2 was 21%, 41%, 28%, and 11%, respectively. In multivariable analyses adjusting for demographic factors, we failed to find a difference between CAC, carotid plaque, and cIMT as predictors of self-reported prevalent CVD (c-statistic 0.70, 95% confidence interval [CI]: 0.62–0.78; c-statistic 0.68, 95% CI: 0.60–0.75, and c-statistic 0.64, CI: 0.56–0.72, respectively). CAC was statistically better than FRS. FRS was the weakest discriminator of self-reported prevalent CVD (c-statistic 0.58).
There was a significant burden of atherosclerosis among individuals with CKD, ascertained by several different imaging modalities. We were unable to find a difference in the ability of CAC, carotid plaque, and cIMT to predict self-reported prevalent CVD.
carotid intima media thickness; coronary artery calcification; kidney; plaque
The risk of cardiovascular disease increases after menopause. Recent evidence suggests that it is possible for HDL to become proatherogenic or dysfunctional in certain situations. Our objective was to evaluate whether the relationship of HDL-C to subclinical cardiovascular disease differed across the menopausal transition, which would provide insight for this increased risk.
Aortic calcification (AC), coronary artery calcification (CAC), carotid plaque and intima media thickness (IMT) were measured in the Study of Women’s Health Across the Nation (SWAN Heart). Women, not using hormone therapy, were stratified into premenopausal or early-perimenopausal (Pre/EP, n=316) and late-perimenopausal or postmenopausal (LP/Post, n=224).
The inverse relationship of HDL-C to subclinical atherosclerosis measures among Pre/EP women was weaker or reversed among LP/post women, adjusted for age, site, race, SBP, glucose, BMI, smoking, menopausal status and LDL-C. Specifically: Multivariable modeling demonstrated an inverse association between HDL-C and AC and IMT, among Pre/EP women; however, the protective effect of HDL-C for AC, left main CAC, carotid plaque and IMT was not seen in LP/Post women. In a small subset (n=53), LP/Post women had more total and small HDL particles, higher triglycerides and more total LDL particles compared to Pre/EP women (p<0.05).
These results suggest that the protective effect of HDL may be diminished as women transition the menopause. Future studies should examine whether this may be due to changes in HDL size, functionality, or related changes in other lipids or lipoproteins.
subclinical cardiovascular disease; lipids; lipoproteins; menopause
Atherosclerosis is the most common pathologic process underlying cardiovascular disease (CVD). It is not well known whether subclinical atherosclerosis is an independent risk factor for lower cognitive function among individuals without clinically evident CVD.
We examined cross-sectional associations between subclinical atherosclerosis and cognitive function in a community-based sample of otherwise healthy adults with plasma homocysteine ≥8.5 µmol/L enrolled in the BVAIT study (n=504, mean age 61 years). Carotid artery intima-media thickness (CIMT), coronary (CAC) and abdominal aortic calcium (AAC) were used to measure subclinical atherosclerosis. Cognitive function was assessed with a battery of neuropsychological tests. A principal components analysis was used to extract five uncorrelated cognitive factors from scores on individual tests, and a measure of global cognition was derived. Multivariable linear regression was used to examine the association between subclinical atherosclerosis and cognitive function, adjusting for other correlates of cognition.
Increasing thickness of CIMT was associated with significantly lower scores on the verbal learning factor (β = −0.07 per 0.1 mm increase CIMT [SE(β)=0.03], p=0.01). CAC and AAC were not individually associated with any of the cognitive factors.
This study provides evidence that increasing CIMT is weakly associated with lower verbal learning abilities but not global cognition in a population of otherwise healthy middle-to-older aged adults with elevated plasma homocysteine but without clinically evident CVD. The association between CIMT and poor verbal learning may pertain particularly to men.
cognitive function; atherosclerosis; cardiovascular disease; memory; verbal learning
The relationship between vitamin D metabolites and subclinical vascular disease is controversial. Because low serum levels of 25-hydroxyvitamin D [25(OH)D] have been associated with many cardiovascular disease (CVD) risk factors, we hypothesized that serum 25(OH)D levels would be inversely associated with inflammation as measured by C-reactive protein (CRP) and with subclinical vascular disease as measured by carotid intimal medial thickness (cIMT) and coronary artery calcification (CAC).
We measured 25(OH)D levels in 650 Amish participants. CAC was measured by computed tomography, and cIMT by ultrasound. The associations of 25(OH)D levels with natural log(CAC+1), cIMT, and natural log(CRP) levels were estimated following adjustment for age, sex, family structure, and season of examination. Additional analyses were carried out adjusting for body mass index (BMI) and other CVD risk factors.
25(OH)D deficiency (<20 ng/ml) and insufficiency (21-30 ng/ml) were common among the Amish (38.2% and 47.7%, respectively). 25(OH)D levels were associated with season, age, BMI, and parathyroid hormone levels. In neither the minimally or fully adjusted analyses were significant correlations observed between 25(OH)D levels and CAC, cIMT, or CRP (R2 < 0.01 for all).
Contrary to our hypothesis, this study failed to detect a cross-sectional association between serum 25(OH)D levels and CAC, cIMT, or CRP. Either there is no causal relationship between 25(OH)D and CVD risk, or, if there is, it may be mediated through mechanisms other than subclinical vascular disease severity.
The aim of this study was to investigate the relationship between obesity, insulin resistance and atherosclerosis in type 2 diabetes mellitus (T2DM) patients. Total 530 patients with T2DM were included. To evaluate the severity of atherosclerosis, we measured the coronary artery calcification (CAC) score, intima-media thickness (IMT) of the common carotid artery, and the ankle-brachial pressure index (ABPI). Subjects were classified according to body mass index (BMI), a marker of general obesity, and waist-to-hip ratio (WHR), a marker of regional obesity. The insulin sensitivity index (ISI) was measured by the short insulin tolerance test. All subjects were classified into four groups, according to BMI: the under-weight group, the normal-weight (NW) group, the over-weight (OW) group, and the obese (OB) group. WHR and systolic blood pressure, triglycerides (TG), HDL-cholesterol (HDL-C), free fatty acids (FFA), fibrinogen, and fasting c-peptide levels were significantly different between BMI groups. TG, HDL-C, FFA, fibrinogen and ISI were significantly different between patients with and without abdominal obesity. In the OW group as well as in the NW group, carotid IMT, ABPI and CAC score were significantly different between patients with and without abdominal obesity. This study indicates that abdominal obesity was associated with atherosclerosis in T2DM patients.
Obesity; Insulin Resistance; Diabetes Mellitus Type 2; Atherosclerosis
Atherosclerosis is the leading cause of cardiovascular disease (CVD). Traditional risk factors can be used to identify individuals at high risk for developing CVD and are generally associated with the extent of atherosclerosis; however, substantial numbers of individuals at low or intermediate risk still develop atherosclerosis.
A case-control study was performed using microarray gene expression profiling of peripheral blood from 119 healthy women in the Multi-Ethnic Study of Atherosclerosis cohort aged 50 or above. All participants had low (<10%) to intermediate (10% to 20%) predicted Framingham risk; cases (N = 48) had coronary artery calcium (CAC) score >100 and carotid intima-media thickness (IMT) >1.0 mm, whereas controls (N = 71) had CAC<10 and IMT <0.65 mm. We identified two major expression profiles significantly associated with significant atherosclerosis (odds ratio 4.85; P<0.001); among those with Framingham risk score <10%, the odds ratio was 5.30 (P<0.001). Ontology analysis of the gene signature reveals activation of a major innate immune pathway, toll-like receptors and IL-1R signaling, in individuals with significant atherosclerosis.
Gene expression profiles of peripheral blood may be a useful tool to identify individuals with significant burden of atherosclerosis, even among those with low predicted risk by clinical factors. Furthermore, our data suggest an intimate connection between atherosclerosis and the innate immune system and inflammation via TLR signaling in lower risk individuals.
Race-specific data for the association between coronary artery calcification (CAC) and carotid intimal medial thickness (IMT) are limited. We sought to compare black-white specific associations of these two measures.
We conducted a population-based study of 379 randomly-selected men aged 40–49 years (84 black and 295 white) from Allegheny County, US (2004–2006). Agatston CAC score was evaluated by electron-beam tomography and carotid IMT was evaluated by ultrasonography.
Compared to white men, black men had similar prevalence of CAC (p=0.56) and higher total carotid IMT (p<0.001). In black and white men, CAC score had significant positive correlations with total carotid IMT (r=0.47 & r=0.24 respectively, p<0.001 for both) as well as the IMT for the common carotid artery (CCA), internal carotid artery and carotid bulb. The associations of CAC with total and CCA IMT were significantly stronger in black (beta=0.07 & beta=0.05 respectively) than white men (beta=0.03 & beta=0.01 respectively) after adjustment for traditional coronary risk factors (p=0.046 & p=0.036 respectively).
In black and white middle-aged men, CAC score had significant positive correlations with total and segmental carotid IMT. CAC was more predictive of total and CCA IMT in black than white men independent of coronary risk factors.
Epidemiology; atherosclerosis; coronary calcification; carotid intimal medial thickness; Caucasian; black
Objective: To evaluate traditional and non-traditional risk factors for subclinical atherosclerosis in systemic lupus erythematosus (SLE).
Methods: A prospective cohort of 78 patients with SLE without overt atherosclerotic disease was studied. SLE clinical and laboratory parameters, disease activity and damage, treatment and traditional risk factors for atherosclerosis were evaluated. At baseline (T1) and after five years' follow up (T2), the serum levels of anti-oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein 65, and anti-ß2-glycoprotein I antibodies and C reactive protein were tested. At T2, intima-media thickness (IMT) was measured using duplex carotid sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT) were assessed.
Results: A thickened intima was seen in 22/78 (28%) patients and plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55 (0.15) mm, respectively. Patients with carotid abnormalities were significantly older, had higher blood pressure and total serum cholesterol levels, and had taken a higher prednisone cumulative dosage than those without any lesions. The carotid abnormalities were associated with renal disease and ECLAM >2 at T1, and with azathioprine treatment. In multivariate analysis, age and cumulative prednisone dose were associated with carotid abnormalities; age, hypertension, and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT.
Conclusions: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose. The role of some traditional risk factors, such as age and hypertension, was also confirmed. The predictive value of the new immunological and inflammatory markers of atherosclerosis seems to be masked by some disease related features.
Tissue factor pathway inhibitor (TFPI) is an endothelial membrane-associated anticoagulant protein. Higher circulating levels might reflect endothelial damage.
We hypothesized an association of higher total TFPI with subclinical atherosclerosis.
Total TFPI was measured in 1000 participants of the Multi-Ethnic Study of Atherosclerosis, a cohort of 6814 men and women without clinical vascular disease, aged 45–84, from 4 ethnic groups. Subclinical atherosclerosis measures were coronary artery calcium (CAC), carotid intima-media thickness (IMT) and ankle-brachial index (ABI).
TFPI was higher with age, male gender, higher LDL-cholesterol, smoking and diabetes, but not ethnicity. Adjusting for risk factors, TFPI in the 4th versus 1st quartile was associated with a 1.2-fold increased risk of detectable CAC (95% CI 1.0–1.4), a 2.1-fold increased risk of CAC >400 Agatston units (95% CI 1.1–4.0) and a 1.6-fold (95% CI 1.1–2.5) increased risk of internal carotid IMT above the 80th percentile, but not with external carotid IMT or low ABI. Findings were consistent across ethnic groups.
In this diverse population, higher total TFPI was associated with prevalent CAC (limited to levels >400 units), and elevated internal carotid IMT, independent of other factors. Higher TFPI may indicate endothelial dysfunction. Further study is needed of TFPI and progression of atherosclerosis.
atherosclerosis; coronary heart disease; tissue factor pathway inhibitor; risk factor
The syndrome of vital exhaustion (VE), characterized by fatigue and irritability, may contribute to an increased risk of atherosclerosis. The aim of the study was to explore sex differences in the interactions of VE with endothelial dysfunction and VE with reduced carotid elasticity, the important contributors to the development of early atherosclerosis, on preclinical atherosclerosis.
The participants were 1002 women and 719 men aged 24-39 examined in the Cardiovascular Risk in Young Finns study. Vital exhaustion was measured using the Maastricht Questionnaire. Preclinical atherosclerosis was assessed by carotid intima-media thickness (IMT), endothelial function was measured by brachial flow-mediated dilatation (FMD), and arterial elasticity by carotid artery compliance (CAC) using ultrasound techniques.
We found a significant CAC x VE interaction for IMT only for the men. Our results imply that high VE level significantly related to high IMT levels among the men with low CAC, but not among the women with low CAC or among the women or men with high CAC. No significant FMD x VE interactions for IMT for the women or men were found.
High VE may exert an effect on IMT for men with impaired arterial elasticity. The results suggest that high vitally exhausted men with reduced arterial elasticity are at increased risk of atherosclerosis in early life and imply men's decreased stress coping in relation to stressful psychological coronary risk factors.
To examine a relationship between alterations of structure and function of the arterial wall in response to glucose-lowering therapy in type 2 diabetes mellitus (DM) after a 1-year follow-up (FU).
Methods and results
In DM (n = 22) and in healthy controls (n = 17), coronary artery calcification (CAC) was assessed with electron beam tomography and carotid intima–media thickness (IMT) with ultrasound, whereas coronary function was determined with positron emission tomography-measured myocardial blood flow (MBF) at rest, during cold pressor testing (CPT), and during adenosine stimulation at baseline and after FU. The decrease in plasma glucose in DM after a mean FU of 14 ± 1.9 months correlated with a lower progression of CAC and carotid IMT (r = 0.48, P ≤ 0.036 and r = 0.46, P ≤ 0.055) and with an improvement in endothelium-related ΔMBF to CPT and to adenosine (r = 0.46, P ≤ 0.038 and r = 0.36, P ≤ 0.056). After adjusting for metabolic parameters by multivariate analysis, the increases in ΔMBF to CPT after glucose-lowering treatment remained a statistically significant independent predictor of the progression of CAC (P ≤ 0.001 by one-way analysis of variance).
In DM, glucose-lowering treatment may beneficially affect structure and function of the vascular wall, whereas the observed improvement in endothelium-related coronary artery function may also mediate direct preventive effects on the progression of CAC.
Cardiovascular disease prevention; Carotid IMT; Coronary artery calcification; Coronary circulation; Endothelium; Diabetes mellitus; Positron emission tomography
Metabolically benign obese individuals have a 10-year cardiovascular disease (CVD) risk comparable to healthy normal weight individuals. However, the burden of subclinical CVD among metabolically benign obese is not well known.
In cross-sectional analyses of 475 mid-life women, we compared common carotid artery intima media thickness (CCA-IMT), aortic pulse wave velocity (aPWV) and coronary (CAC) and aortic calcification (AC) among three groups: healthy normal weight, metabolically benign overweight/obese (<3 metabolic syndrome components/elevated CRP), and at-risk overweight/obese (≥3 metabolic syndrome components/elevated CRP).
The mean (SD) CCA-IMT and aPWV were lowest in the normal weight group (n=145), followed by the benign overweight/obese (n=260) and at-risk overweight/obese (n=70) groups [CCA-IMT: 0.64 (0.08) vs. 0.68 (0.09) vs. 0.73 (0.13) mm, p<0.001; aPWV: 731.0 (176.4) vs. 809.9 (182.3) vs. 875.7 (228.8) cm/s, p<0.001]. Similar results were found for the frequency (%) of women with increased CAC and AC [CAC: 13 (9%) vs. 53(20%) vs. 28(40%), p<0.001; AC: 47(32%) vs. 130 (50%) vs. 55(79%), p<0.001]. These differences remained significant after multivariable adjustment. Further adjustment for BMI attenuated the statistical significance of differences in aPWV and calcification between benign and at-risk overweight/obese women, but had little effect on the magnitude of these differences.
Metabolically benign overweight/obese women have a significantly greater subclinical CVD burden than normal weight women, despite published data finding similar CVD event rates between the two groups. Prospective studies tracking the progression of subclinical atherosclerosis to clinical CVD in these women are needed.
Obesity phenotypes; subclinical atherosclerosis; carotid intima media thickness; pulse wave velocity; coronary calcification; aortic calcification
Objectives. Cardiovascular disease remains the major cause of death in SLE. We assessed the degree to which cardiovascular risk factors (CVRFs) and disease activity were associated with 2-year changes in measures of subclinical atherosclerosis.
Methods. One hundred and eighty-seven SLE patients participating in a placebo-controlled trial of atorvastatin underwent multi-detector CT [for coronary artery calcium (CAC)] and carotid duplex [for carotid intima–media thickness (IMT) and carotid plaque] twice, 2 years apart. During the 2 years, patients were assessed every 3 months for CVRF. Both groups were combined for analysis, as atorvastatin did not differ from placebo in preventing progression of coronary calcium. We examined the correlation between these clinical measures and progression of CAC, IMT and plaque during the follow-up period.
Results. In an analysis adjusting for age, gender and ethnicity, CAC progression was positively associated with total serum cholesterol measured over the 2-year period (P = 0.04) and smoking (P = 0.003). Carotid IMT progression was associated with systolic BP (P = 0.003), high-sensitivity CRP (hsCRP) (P = 0.013) and white blood cell (WBC) count (P = 0.029). Carotid plaque progression, defined as patients without carotid plaque at baseline with subsequent development of plaque at follow-up, was associated with systolic BP (P = 0.003), WBC count (P = 0.02), physician's global assessment (P = 0.05), blood lymphocyte count (P = 0.048), urine protein (P = 0.017) and duration of SLE (P = 0.019).
Conclusion. Our data did not provide evidence of an association between measures of SLE disease activity (SLEDAI, anti-dsDNA, anti-phospholipid and treatment) and progression of subclinical atherosclerosis. Age and hypertension were associated with the progression of carotid IMT and plaque. Age, smoking and cholesterol were associated with progression of CAC.
Systemic lupus erythematosus; Helical computed tomography; Coronary artery calcium; Carotid intima–media thickness; Carotid plaque; Inflammation; Atherosclerosis; Carotid duplex; Coronary artery disease; Statins
This study aims to explore the interactive effect of vital exhaustion (VE) and endothelial dysfunction on preclinical atherosclerosis, assessed by carotid intima-media thickness (IMT). Furthermore, interaction between VE and carotid elasticity is examined. Participants were 1,596 young healthy adults from the Cardiovascular Risk in Young Finns study. Endothelial dysfunction was measured by brachial flow-mediated dilatation (FMD), and carotid elasticity by carotid artery compliance (CAC). Significant interactions between FMD and VE, and between CAC and VE, for IMT were found in participants with the very lowest FMD and CAC. Thus, VE may be harmful if the endothelium is not working properly.
chronic stress; vital exhaustion; intima-media thickness; flow-mediated dilatation; carotid artery compliance; atherosclerosis
The goal of this study was to compare internal carotid artery (ICA) intima-media thickness (IMT) with common carotid artery (CCA) IMT as global markers of cardiovascular disease (CVD).
Cross-sectional measurements of the mean CCA IMT and maximum ICA IMT were made on ultrasound images acquired from the Framingham Offspring cohort (n = 3316; mean age, 58 years; 52.7% women). Linear regression models were used to study the associations of the Framingham risk factors with CCA and ICA IMT. Multivariate logistic regression models and receiver operating characteristic (ROC) curve analysis were used to compare the associations of prevalent CVD with CCA and ICA IMT and determine sensitivity and specificity.
The association between age and the mean CCA IMT corresponded to an increase of 0.007 mm/y; the increase was 0.037 mm/y for the ICA IMT. Framingham risk factors accounted for 28.6% and 27.5% of the variability in the CCA and ICA IMT, respectively. Age and gender contributed 23.5% to the variability of the CCA IMT and 22.5% to that of the ICA IMT, with the next most important factor being systolic blood pressure (1.9%) for the CCA IMT and smoking (1.6%) for the ICA IMT. The CCA IMT and ICA IMT were statistically significant predictors of prevalent CVD, with the ICA IMT having a larger area under the ROC curve (0.756 versus 0.695).
Associations of risk factors with CCA and ICA IMT are slightly different, and both are independently associated with prevalent CVD. Their value for predicting incident cardiovascular events needs to be compared in outcome studies.
atherosclerosis; carotid artery; disease prevalence; intima-media thickness; risk factors