HIV-infected patients are at increased risk for cardiovascular disease, which may be mediated in part by inflammation. This study aimed to evaluate the risk factors of carotid plaque, and clinical factors associated with carotid atherosclerosis measured by carotid intima-medial thickness (cIMT) in HIV patients.
Materials and Methods
Clinical and cardiometabolic factors as well as cIMT were prospectively measured in 145 HIV-infected participants who had received combined antiretroviral therapy for ≥6 months. The mean value of the bilateral average cIMT level was used as Mean-IMT in the analysis, and the greatest value among the measured cIMT levels was used as Max-IMT.
Among 145 patients, 34 (23.4%) had carotid plaque. Multivariate logistic regression analysis revealed three independent risk factors of carotid plaque: old age [odds ratio (OR) 6.16, 95% confidence interval (CI) 1.09-34.88; p=0.040], hypertension (OR 12.62, 95% CI 1.72-92.49; p=0.013) and higher low-density lipoprotein cholesterol (LDL-C) (OR 1.08, 95% CI 1.01-1.16; p=0.039). Levels of estimated glomerular filtration rate were inversely associated with Mean-IMT (r=-0.379, p<0.001) and Max-IMT (r=-0.389, p<0.001). Stepwise multivariate regression analyses revealed that age, total cholesterol and fasting glucose were positively correlated with cIMT, independent of other risk factors.
The presence of hypertension, old age and a higher level of LDL-C were independent risk factors of carotid plaque among HIV-infected subjects.
Carotid plaque; carotid artery intima-media thickness; atherosclerosis; combined antiretroviral therapy; HIV infection
We investigated the relationship of the Herpesviridiae with inflammation and subclinical atherosclerosis in HIV-infected patients.
Prospective study including virologically suppressed HIV-infected patients. IgG antibodies against herpesviruses, carotid intima-media thickness (cIMT), endothelial function through flow-mediated dilatation (FMD) of the brachial artery, and blood atherosclerosis biomarkers (hsCRP, TNF-α, IL-6, MCP-1, MDA, sCD14, sCD163, VCAM-1, ICAM-1, D-dimer, and PAI-1) were measured.
136 patients with HIV viral load <200 copies/ml were included. 93.4% patients were infected with herpes simplex virus type-1, 55.9% with herpes simplex virus type-2, 97.1% with varicella-zoster virus, 65.4% with human herpesvirus-6, 91.2% with cytomegalovirus, and 99.3% with Epstein-Barr virus. Previous AIDS diagnosis was associated with higher cytomegalovirus IgG titers (23,000 vs 17,000 AU, P = 0.011) and higher varicella-zoster virus IgG titers (3.19 vs 2.88 AU, P = 0.047), and there was a positive correlation of the Framingham risk score with IgG levels against cytomegalovirus (Spearman's Rho 0.216, P = 0.016) and Herpes simplex virus-2 (Spearman's Rho 0.293, P = 0.001). IgG antibodies against cytomegalovirus correlated in adjusted analysis with the cIMT (P = 0.030). High seropositivity for varicella-zoster virus (OR 2.91, 95% CI 1.05–8.01, P = 0.039), and for cytomegalovirus (OR 3.79, 95% CI 1.20–11.97, P = 0.023) were predictors for the highest quartile of the cIMT in adjusted analyses. PAI-1 levels were independently associated with cytomegalovirus IgG titers (P = 0.041), IL-6 and ICAM-1 levels with varicella-zoster virus IgG (P = 0.046 and P = 0.035 respectively), and hsCRP levels with Herpes simplex virus-2 IgG (P = 0.035).
In virologically suppressed HIV-infected patients, antibody responses against herpesviruses are associated with subclinical atherosclerosis, and with increased inflammation and coagulation biomarkers.
Previous research has demonstrated an increase in carotid intima–media thickness (cIMT) in HIV-infected individuals compared to controls. However, the reason for this increased level of subclinical vascular disease is unknown.
To identify HIV-related risk factors for increased cIMT.
We evaluated the relationship between HIV-related characteristics (including markers of HIV disease severity and use of antiretroviral therapy) and cIMT measurements in the internal/bulb and common carotid regions among 538 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). We used Bayesian model averaging to estimate the posterior probability of candidate HIV and non-HIV-related risk factors being true predictors of increased cIMT. Variables with a posterior probability of more than 50% were used to develop a selected regression model for each of the anatomic regions.
For common cIMT, the Bayesian model selection process identified age, African-American race, and systolic and diastolic blood pressure with probability more than 95%, HDL cholesterol with probability 85% and Hispanic ethnicity with probability 51%. Among the HIV-related factors included in the analysis, only tenofovir use was selected (51% probability). In the selected model, duration of tenofovir use was associated with lower common cIMT (−0.0094 mm/year of use; 95% confidence interval: −0.0177 to −0.0010). For internal cIMT, no HIV-related risk factors were above the 50% posterior probability threshold.
We observed an inverse association between duration of tenofovir use and common carotid cIMT. Whether this association is causal or due to confounding by indication needs further investigation.
atherosclerosis; carotid intima–media thickness; HIV; tenofovir
Rheumatoid arthritis (RA) patients have increased mortality and morbidity as a result of cardiovascular and cerebrovascular disease. What is not clear, however, is either how early accelerated atherosclerosis begins in RA or how soon risk factors must be rigorously controlled. Furthermore, given the strong relationship of vascular disease to RA mortality and of inflammation to the accelerated atherosclerosis associated with RA, it is important to evaluate indices that could serially and noninvasively quantify atherosclerotic disease in RA patients. The carotid intima-media thickness (cIMT) and plaque, measured by ultrasound, correlate closely with direct measurement of the local and systemic atherosclerotic burden. To investigate the presence of subclinical atherosclerosis in the early stages of RA, the cIMT and plaque were measured using carotid duplex scanning in 40 RA patients with disease duration < 12 months and in 40 control subjects matched for age, sex and established cardiovascular risk factors. Patients with RA had significantly higher average cIMT values and more plaque than the control group (cIMT 0.64 ± 0.13 mm versus 0.58 ± 0.09 mm, respectively; P = 0.03). In RA patients, the cIMT was predicted by age and C-reactive protein level at first presentation to the clinic (R2 = 0.64). C-reactive protein was associated with age of disease onset and history of smoking. Since inflammation has been shown to predate onset of clinical RA, the accelerated atherogenic process related to inflammation may precede RA symptom onset.
Conflicting information exists regarding the association between hsCRP and the progression of early stages of atherosclerosis. The purpose of the study was to investigate the association of high sensitiviy c-reactive protein (hsCRP) along with major cardiovascular (CV) risk factors on early carotid atherosclerosis progression in a large, population-based cohort study.
The study cohort included 839 young adults (aged 24 to 43 years, 70% white, 42% men) enrolled in Bogalusa Heart Study, who in 2001-2002 attended baseline examination with measurements of CV risk factors. Progression of carotid artery intima-media thickness (IMT) was assessed during a mean follow-up of 2.4 years.
Carotid artery IMT progression rates were as follows: composite carotid artery = 9.2 ± 52 μm/y, common carotid artery = 0.0 ± 51 μm/y, carotid bulb = 8.8 ± 103 μm/y, and internal carotid artery = 18.9 ± 81 μm/y. Elevated baseline hsCRP, reflecting an inflammatory state, showed independent association with composite carotid artery IMT progression. Increased age, systolic blood pressure, fasting glucose, LDL cholesterol, and current smoking were other risk associates of carotid artery IMT progression in young adults, indicating an underlying burden on the CV system by multiple risk factors.
In this population-based study, we observed independent categorical association of increased hsCRP with carotid artery IMT progression in young adults. This study underlines the importance of assesssing hsCRP levels along with smoking and traditional CV risk factor profiles in asymptomatic young adults.
Carotid artery intima-media thickness progression; cardiovascular risk; c-reactive protein; epidemiology; young adults
HIV-seropositive patients are at higher risk for atherosclerosis than HIV-seronegative persons. This has been variably attributed to antiretroviral drug toxicity, immunodeficiency, and/or HIV-associated inflammation. To evaluate the contributions of these factors to HIV-associated atherosclerosis, we assessed carotid artery intima-media thickness (IMT) in a diverse cohort of HIV-seronegative and seropositive adults, including a unique group of HIV-infected patients who were untreated, had undetectable viral loads and had preserved CD4+ T cell counts (HIV controllers).
Methods and Results
Carotid IMT was measured in 494 subjects, including 33 HIV controllers and 93 HIV-seronegative controls. HIV controllers had higher IMT than seronegative controls even after adjustment for traditional risk factors (p=0.003). IMT in controllers was similar to antiretroviral-untreated patients with detectable viremia. Across all subjects, IMT was strongly associated with the presence of HIV disease rather than viral load or CD4+ T cell count. C-reactive protein was higher in HIV controllers than HIV-seronegative persons. Antiretroviral drug exposure was also associated with higher IMT.
Increased atherosclerosis with HIV infection can occur in the absence of antiretroviral therapy, detectable viremia, or overt immunodeficiency. Chronic inflammation—which is higher in controllers than in HIV-uninfected persons—may account for early atherosclerosis in these patients.
Objective: Women with Turner syndrome (TS) have greater carotid artery intima-media thickness (cIMT) known to be a risk factor for atherosclerosis in adults. To determine whether there are risk factors for atherosclerosis in children with TS, we compared cIMT, anthropometric and metabolic parameters between children with TS and healthy controls.
Methods: Data of children with TS with XO karyotype (n=24, mean age: 11.6±3.6) were compared with those of healthy children (n=24, mean age: 10.5±3.6) with respect to anthropometric parameters, lipid levels, insulin resistance and cIMT which was measured by high resolution B-mode ultrasonography.
Results: Mean age and cIMT values were similar in the two groups of children. However in children with TS, fasting glucose (p=0.01), total cholesterol (p=0.006), triglyceride (p=0.04) levels and HDL-cholesterol (p=0.002) levels were higher than those of controls. In the TS group, cIMT correlated positively with LDL-cholesterol (r=0.435, p=0.034) and with systolic blood pressure (r=0.430, p=0.036) and negatively with HDL-cholesterol (r=-0.518, p=0.01). In stepwise regression analysis, HDL-cholesterol emerged as a significant predictor of cIMT (b= -0.518, p=0.01) contributing to 26.8 % of its variability.
Conclusion: The systolic blood pressure and dyslipidaemia were shown to be risk factors for atherosclerosis in children with TS.
Conflict of interest:None declared.
children; Turner syndrome; cardiovascular disease; carotid intima-media thickness
To replicate the association of variants in RYR3 gene with common carotid intima-media thickness (cIMT), a surrogate marker of atherosclerosis, we genotyped single nucleotide polymorphisms (SNPs) rs2229116 and rs7177922 in a sub-population of 244 HIV-positive and HIV-negative men. SNP rs2229116 was associated with common cIMT in HIV infected white men after adjusting for age and use of stavudine (d4T). The association was more evident at younger ages and decreased among older individuals.
To investigate the effects of aging and smoking on carotid intima-media thickness (cIMT) among patients with and without HIV.
Data from a community sample of HIV-infected and HIV-uninfected participants were analyzed. Carotid intima-media thickness was measured via carotid ultrasound and smoking history was obtained via patient interview.
Data on 166male and female participants with stable HIV-infection and 152 healthy HIV-uninfected participants were analyzed. Among the HIV-infected and HIV-uninfected participants, a significant association was observed between age and cIMT [r=0.51, P<0.0001 (HIV), r=0.39, P<0.0001, (non-HIV)], and between smoking burden and cIMT [r=0.42, P<0.0001 (HIV), r=0.24, P=0.003 (non-HIV)]. In multivariate regression modeling among all participants (HIV and non-HIV), a significant three-way interaction was observed between age, smoking burden, and HIV status with respect to cIMT (P<0.010), controlling for gender, race and traditional cardiovascular disease (CVD) risk factors, such that increased cIMT was associated with increased smoking burden and age to a greater degree among HIV-infected vs. HIV-uninfected participants. Among HIV-infected participants a significant interaction between smoking burden and age with respect to cIMT was seen (P=0.027), controlling for race, gender, CVD risk factors, immunological function and antiretroviral therapy use.
A significant interaction between HIV, age and smoking on cIMT was observed, suggesting that HIV-infection modifies the relationship of age and smoking on cIMT in this population. These findings emphasize the need to encourage smoking cessation in this population, due to its deleterious effect on subclinical atherosclerosis in older HIV-infected patients.
HIV; Aging; Cardiovascular Diseases; Smoking
It has been previously documented that carotid intima-media thickness (cIMT) is a predictor of cardiovascular disease. The aim of this study was to identify clinical parameters associated with an increased cIMT treated hypertensive women. Female patients (n = 116) with essential hypertension, aged 40–65 years, were included in this study. Vascular ultrasound was performed and the patients were divided into two groups according to the values of cIMT (< or ≥0.9 mm). Patients with greater cIMT presented significantly higher systolic blood pressure and pulse pressure. Serum HDL-cholesterol was significantly lower and CRP was significantly higher in the same group. There was a significant correlation between cIMT and age (r = 0.25, P = 0.007), systolic blood pressure (r = 0.19, P = 0.009), pulse pressure (r = 0.30, P = 0.001), and LDL-cholesterol (r = 0.19, P = 0.043). cIMT was correlated to CRP (r = 0.31, P = 0.007) and negatively correlated to HDL-cholesterol (r = 0.33, P = 0.001). In logistic regression, only HDL-cholesterol, CRP, and pulse pressure were shown to be independent variables associated to increased cIMT. In conclusion, pulse pressure, HDL-cholesterol, and CRP are variables correlated with cIMT in treated hypertensive women.
Established rheumatoid arthritis (RA) is associated with a doubled cardiovascular risk. However, data about the cardiovascular risk in early RA are scarce. Preclinical atherosclerosis can be reliably assessed with the carotid intima media thickness (cIMT), and the cIMT is a well-validated predictor of cardiovascular events. The cIMT was therefore used in a recent controlled, prospective study in patients with early RA. Surprisingly, an increased cardiovascular risk at baseline could not be demonstrated whereas cIMT progression appeared to be comparable with the general population. Obviously, this study underscores the need for further large-scale investigations to solve the emerging discrepancy with the existing literature.
Objective. We aimed to determine the prevalence of excess body mass in juvenile idiopathic arthritis (JIA) children and to investigate the influence of obesity into the early, subclinical changes in cardiovascular system in these patients. Methods. Fifty-eight JIA patients, aged median 13 years, were compared to 36 healthy controls. Traditional cardiovascular risk factors and inflammatory markers (hsCRP, IL-6, TNFα, adiponectin) were studied together with IMT (intima-media thickness), FMD (flow mediated dilation), and LVMi (left ventricle mass index) as surrogate markers of subclinical atherosclerosis. Results. Thirteen JIA children (22%) were obese and had increased systolic blood pressure, cholesterol, triglycerides, insulin, HOMA, hsCRP, and IL-6 compared to nonobese JIA and controls. FMD was decreased compared to nonobese JIA and controls, whereas IMT and LVMi were increased. In multivariate regression analysis, TNFα, SDS-BMI, and systolic blood pressure were independent predictors of early CV changes in JIA. Conclusions. Coincident obesity is common in JIA children and is associated with insulin resistance, dyslipidemia, and increased levels of inflammatory markers leading to early changes in cardiovascular system. Thus, medical care of children with JIA should include strategies preventing cardiovascular disease by maintenance of adequate body weight.
Systematic differences between readers or equipment in imaging studies are not uncommon; failure to account for such differences when using Carotid Ultrasonography may introduce bias into associations between carotid intima media thickness (cIMT) and outcomes. We demonstrate the impact of this source of systematic measurement error (SME) using data on 5,521 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and 661 participants from the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). Participants were between 37 and 78 years old. Two outcomes were considered: (1) the effect of HIV infection on cIMT (between study) and (2) the association of cIMT with cardiovascular events (within study). All estimates were adjusted for demographics (age, gender, and ethnicity) and for traditional cardiovascular disease risk factors (smoking, blood pressure, diabetes and cholesterol). When comparing the FRAM and MESA cohorts to estimate the association of HIV infection on common cIMT, accounting for machine and reader variability (between study variability) reduced the difference associated with HIV infection from +0.080 mm (95% Confidence Interval (CI):0.065–0.095) to +0.037 mm (95% CI:0.003 to 0.072) while internal cIMT declined from +0.254 mm (95% CI:0.205–0.303) to +0.192 mm (95% CI:0.076–0.308). Attenuation of the association between cIMT and cardiovascular endpoints occurred when within study reader variability was not accounted for. The effect of SME due to use of multiple readers or machines is most important when comparisons are made between two different study populations. Within-cohort measurement error dilutes the association with events.
Carotid intima media thickness; Measurement error; Bias; Carotid ultrasonography
Single nucleotide polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), monocyte chemoattractant protein-1 (MCP-1) and apolipoprotein E (ApoE) genes appear to be a genetic risk factor for atherosclerosis. Common carotid intima-media thickness (cIMT) provides information on the severity of atherosclerosis.
To investigate the relationship between cIMT and gene polymorphisms associated with atherosclerosis in Turkish patients with coronary artery disease (CAD).
Sixty-two patients with angiographically diagnosed stable CAD were divided into two groups according to their cIMT values (group 1: n=35, cIMT of 1 mm or greater; group 2: n=27, cIMT of less than 1 mm). MTHFR 677 C/T, VEGF–460 C/T, eNOS 894 G/T, MCP-1–2518 A/G and ApoE (E2, E3 and E4) gene polymorphisms (where A is adenine, C is cytosine, G is guanine and T is thymine) were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Evaluations of cardiovascular risk factors and coronary atherosclerotic lesions were performed in all patients. Serum homocysteine and high-sensitivity C-reactive protein were measured and compared between the two groups.
Serum high-sensitivity C-reactive protein (P=0.04) and homocysteine (P=0.006) levels were higher in group 1 than in group 2. The ratio of multivessel CAD and previous myocardial infarction was significantly higher in group 1 than in group 2 (P=0.014). In the study population, no significant difference in cIMT was observed according to the polymorphisms studied. Only hyperhomocysteinemia (OR 1.17 [95% CI 1.01 to 1.35], P=0.033) and previous myocardial infarction (OR 3.76 [95% CI 1.10 to 12.81], P=0.034) maintained a significant correlation with cIMT on multiple logistic regression analysis.
cIMT is increased in patients with hyperhomocysteinemia, inflammation and extended CAD. MTHFR 677 C/T, VEGF–460 C/T, eNOS 894 G/T, MCP-1–2518 A/G and ApoE single nucleotide polymorphisms were not associated with increased cIMT.
Atherosclerosis-related genes; Carotid intima-media thickness; Coronary artery disease; Homocysteine
Carotid artery intima-media thickness (IMT) is a marker of cardiovascular disease associated with incident stroke. We study whether IMT rate-of-change is associated with stroke.
Materials and Methods
We studied 5028 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) composed of whites, Chinese, Hispanic and African-Americans free of cardiovascular disease. In this MESA IMT progression study, IMT rate-of-change (mm/year) was the difference in right common carotid artery (CCA) far-wall IMT (mm) divided by the interval between two ultrasound examinations (median interval of 32 months). CCA IMT was measured in a region free of plaque. Cardiovascular risk factors and baseline IMT were determined when IMT rate-of-change was measured. Multivariable Cox proportional hazards models generated Hazard risk Ratios (HR) with cardiovascular risk factors, ethnicity and education level/income as predictors.
There were 42 first time strokes seen during a mean follow-up of 3.22 years (median 3.0 years). Average age was 64.2 years, with 48% males. In multivariable models, age (HR: 1.05 per year), systolic blood pressure (HR 1.02 per mmHg), lower HDL cholesterol levels (HR: 0.96 per mg/dL) and IMT rate-of-change (HR 1.23 per 0.05 mm/year; 95% C.L. 1.02, 1.48) were significantly associated with incident stroke. The upper quartile of IMT rate-of-change had an HR of 2.18 (95% C.L.: 1.07, 4.46) compared to the lower three quartiles combined.
Common carotid artery IMT progression is associated with incident stroke in this cohort free of prevalent cardiovascular disease and atrial fibrillation at baseline.
Ultrasonography; Risk Factors; Carotid Arteries; Carotid Intima Media Thickness; stroke
To evaluate associations between traditional cardiovascular disease (CVD) risk factors, inflammatory markers, and markers of HIV disease activity with ultrasonographic measures of CVD risk in patients with HIV who are not receiving antiretroviral therapy (ART).
Cross-sectional, baseline evaluation of ART-naïve HIV-infected individuals without known CVD or diabetes mellitus enrolled in a randomized ART treatment trial.
Prior to ART initiation, carotid artery intima-media thickness (CIMT) and brachial artery flow-mediated dilation (FMD) were measured. Additional parameters included CD4 cell count, HIV viral load, body composition, lipoproteins, and inflammatory markers. Associations with common CIMT, bifurcation CIMT, presence of carotid artery lesions, and brachial artery FMD were evaluated.
The 331 enrolled subjects were a median (1st–3rd quartile) of 36 (28–45) years old. Common and bifurcation CIMT values were higher and lesions more prevalent with older age (p <0.001). FMD was lower with older age (p =0.009). Those with a Framingham Risk Score >6%/10 years (N =44) had higher common and bifurcation CIMT (p <0.001), carotid lesion prevalence (p <0.001), and lower FMD (p =0.035). Independent associations with common CIMT were identified for increasing age, height, weight, small LDL particles, and black race; these were similar for bifurcation CIMT. Presence of carotid artery lesions was associated with increasing age, presence of metabolic syndrome, interleukin-6, and lower HIV-1 RNA.
In a contemporary cohort of ART-naive HIV-infected individuals, ultrasonographic measures of CVD risk were more strongly associated with traditional risk factors than CD4 cell counts, HIV replication, or inflammatory markers.
atherosclerosis; carotid arteries; endothelial function; human immunodeficiency virus; inflammation
Since inflammation is an important contributor to atherosclerosis, gene variants mediating inflammation are of interest. We investigated gene variants in acute phase serum amyloid-A (SAA), a sensitive indicator of inflammatory activity, and their associations with cardiovascular disease (CVD) and HDL cholesterol. Interaction of the SAA genes with genetic variants of their regulators, IL-1, IL-6 and TNF-α in influencing CVD was also explored.
SNPs characterizing common variation in the SAA1 and SAA2 genes were genotyped in European-(EA) and African-American (AA) participants (n=3969 and n=719) of the Cardiovascular Health Study. Using linear and Cox proportional hazards regression, we assessed associations of SNPs with baseline carotid artery intima-media thickness (cIMT) and risk of incident myocardial infarction, ischemic stroke, total CVD events or mortality during ~14 years of follow-up.
No associations between SAA SNPs and outcomes were observed in EA, with the exception of total CVD events; each rs4638289 minor allele was associated with an increased risk in obese individuals, HR=1.2 (95%CI: 0.98-1.4; p=0.086) and decreased risk among non-obese, HR=0.9 (95%CI: 0.8-0.99; p=0.026). In AA, we observed modest associations between SAA SNPs and cIMT, potentially modified by HDL. SAA SNPs were also associated with lower HDL in EA and AA. Suggestive gene-gene interaction findings for cIMT in AA and CVD mortality in EA were not significant in subsequent model selection tests.
Associations of SAA SNPs with cIMT, HDL and total CVD events were identified, unadjusted for multiple testing. These findings should be regarded as hypothesis-generating until confirmed by other studies.
acute phase reactants; carotid IMT; myocardial infarction; ischemic stroke; genetic variants
Carotid intima–media thickness (CIMT) and plaque information can improve coronary heart disease (CHD) risk prediction when added to traditional risk factors (TRF). However, obtaining adequate images of all carotid artery segments (A-CIMT) may be difficult. Of A-CIMT, the common carotid artery intima–media thickness (CCA-IMT) is relatively more reliable and easier to measure. We evaluated whether CCA-IMT is comparable to A-CIMT when added to TRF and plaque information in improving CHD risk prediction in the Atherosclerosis Risk in Communities (ARIC) study.
Methods and results
Ten-year CHD risk prediction models using TRF alone, TRF + A-CIMT + plaque, and TRF + CCA-IMT + plaque were developed for the overall cohort, men, and women. The area under the receiver operator characteristic curve (AUC), per cent individuals reclassified, net reclassification index (NRI), and model calibration by the Grønnesby–Borgan test were estimated. There were 1722 incident CHD events in 12 576 individuals over a mean follow-up of 15.2 years. The AUC for TRF only, TRF + A-CIMT + plaque, and TRF + CCA-IMT + plaque models were 0.741, 0.754, and 0.753, respectively. Although there was some discordance when the CCA-IMT + plaque- and A-CIMT + plaque-based risk estimation was compared, the NRI and clinical NRI (NRI in the intermediate-risk group) when comparing the CIMT models with TRF-only model, per cent reclassified, and test for model calibration were not significantly different.
Coronary heart disease risk prediction can be improved by adding A-CIMT + plaque or CCA-IMT + plaque information to TRF. Therefore, evaluating the carotid artery for plaque presence and measuring CCA-IMT, which is easier and more reliable than measuring A-CIMT, provide a good alternative to measuring A-CIMT for CHD risk prediction.
CIMT; Plaque; Risk prediction
Progranulin and C1q/TNF-related protein-3 (CTRP3) were recently discovered as novel adipokines which may link obesity with altered regulation of glucose metabolism, chronic inflammation and insulin resistance.
Research Design and Methods
We examined circulating progranulin and CTRP3 concentrations in 127 subjects with (n = 44) or without metabolic syndrome (n = 83). Furthermore, we evaluated the relationship of progranulin and CTRP3 levels with inflammatory markers and cardiometabolic risk factors, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), estimated glomerular filtration rate (eGFR), and adiponectin serum concentrations, as well as carotid intima-media thickness (CIMT).
Circulating progranulin levels are significantly related with inflammatory markers, hsCRP (r = 0.30, P = 0.001) and IL-6 (r = 0.30, P = 0.001), whereas CTRP3 concentrations exhibit a significant association with cardiometabolic risk factors, including waist circumference (r = −0.21), diastolic blood pressure (r = −0.21), fasting glucose (r = −0.20), triglyceride (r = −0.34), total cholesterol (r = −0.25), eGFR (r = 0.39) and adiponectin (r = 0.26) levels. Serum progranulin concentrations were higher in patients with metabolic syndrome than those of the control group (199.55 [179.33, 215.53] vs. 185.10 [160.30, 204.90], P = 0.051) and the number of metabolic syndrome components had a significant positive correlation with progranulin levels (r = 0.227, P = 0.010). In multiple regression analysis, IL-6 and triglyceride levels were significant predictors of serum progranulin levels (R2 = 0.251). Furthermore, serum progranulin level was an independent predictor for increased CIMT in subjects without metabolic syndrome after adjusting for other cardiovascular risk factors (R2 = 0.365).
Serum progranulin levels are significantly associated with systemic inflammatory markers and were an independent predictor for atherosclerosis in subjects without metabolic syndrome.
Cardiovascular disease contributes to mortality in type 1 diabetes mellitus, but the specific pathophysiological mechanisms remain to be established. We recently showed that the endothelial glycocalyx, a protective layer of proteoglycans covering the endothelium, is severely perturbed in type 1 diabetes, with concomitantly increased plasma levels of hyaluronan and hyaluronidase. In the present study, we evaluated the relationship between hyaluronan and hyaluronidase with carotid intima-media thickness (cIMT), an established surrogate marker for cardiovascular disease.
Subjects and methods
Non-smoking type 1 diabetes patients without micro- or macrovascular complications and matched controls were recruited and cIMT of both carotid arteries was measured. To evaluate the relationship between cIMT and hyaluronan and hyaluronidase as well as other parameters, uni- or multivariate regression analyses were performed.
We included 99 type 1 diabetes patients (age 10–72 years) and 99 age- and sex-matched controls. Mean cIMT, HbA1c, high sensitivity C-reactive protein, hyaluronan and hyaluronidase were significantly increased in type 1 diabetes vs controls. Plasma hyaluronan and hyaluronidase were correlated in type 1 diabetes. In univariate regression analyses, mean IMT was associated with plasma hyaluronan, age and male sex, whereas after multivariate analysis only age and sex remained statistically significant.
We conclude that type 1 diabetes patients show structural changes of the arterial wall associated with increased hyaluronan metabolism. These data may lend further support to altered glycosaminoglycan metabolism in type 1 diabetes as a potential mechanism involved in accelerated atherogenesis.
Hyaluronan; Hyaluronidase; Intima-media thickness; Type 1 diabetes mellitus
Carotid intima-media thickness (cIMT) is an independent predictor of cardiovascular risk. Furthermore, ethnicity and gender-specific normative data are required to assess cIMT, which are not available for Andean-Hispanics. In addition, data regarding correlates of subclinical atherosclerosis in ethnic population are needed.
We studied 1448 adults enrolled in a population-based study in Peru. cIMT and carotid plaque were measured with high-resolution ultrasonography. A healthy reference sample (n=472) with no cardiovascular disease, normal weight and normal metabolic parameters was selected to establish normative cIMT values. Correlates of abnormal cIMT and carotid plaque were assessed in the entire population.
In the reference sample, 95th-percentile cIMT values were both age and gender-dependent. In stepwise regression, selected predictors of increasing cIMT were: older age, impaired fasting glucose, diabetes mellitus, higher systolic blood pressure, higher LDL-cholesterol, smoking and male gender. Predictors of carotid plaque included older age, male gender, higher systolic blood pressure, lower diastolic blood pressure and higher LDL-cholesterol. HDL-cholesterol and C-reactive protein were not associated with cIMT or carotid plaque. The lack of association with HDL-cholesterol was confirmed using high performance liquid chromatography.
We present ethnic-specific cutoffs for abnormal cIMT applicable to Andean-Hispanics and correlates of subclinical atherosclerosis in this population. Pending longitudinal studies, our data supports several risk associations seen in other populations and can be used to identify Andean-Hispanics at increased risk for atherosclerotic cardiovascular disease. The lack of association between HDL-C and cIMT or carotid plaque in this population requires further investigation.
carotid intima-media thickness; Andean-Hispanics; definitions; cardiovascular disease; Latin America
Relationship of hepatitis C virus (HCV) infection with an increased risk of cardiovascular disease (CVD) in HIV-infected patients remains controversial. We evaluated endothelial function and subclinical atherosclerosis in HIV-infected patients with and without HCV.
Flow-mediated dilatation (FMD) of the brachial artery and circulating levels of cell adhesion molecules (CAM) were measured in HCV/HIV-coinfected and HIV-monoinfected patients. Subclinical atherosclerosis was assessed by carotid intima-media thickness (cIMT).
63 (31%) HCV/HIV-coinfected and 138 (69%) HIV-monoinfected patients were included. Median soluble vascular CAM-1 (sVCAM-1) and intercellular CAM-1 (sICAM-1) levels were significantly higher in HIV/HCV-coinfected patients (P < 0.001 for both cases). Median (interquartile range) FMD was 6.21% (2.86-9.62) in HCV/HIV-coinfected and 5.54% (2.13-9.13) in HIV-monoinfected patients (P = 0.37). Adjustment for variables associated with HCV and FMD disclosed similar results. FMD correlated inversely with cIMT and age. Carotid IMT did not differ between HCV/HIV-coinfected and HIV-monoinfected patients in unadjusted (0.61 [0.55-0.65] mm vs 0.60 [0.53-0.72] mm; P = 0.39) or adjusted analyses.
HCV infection was associated with higher levels of sICAM-1 and sVCAM-1, but no evidence of increased subclinical atherosclerosis was found when endothelial function was evaluated through FMD, or when assessing the cIMT.
Upper body fat is associated with increased cardiometabolic risk. More recently, neck circumference (NC) and/or neck fat have been associated with hyperlipidemia, impaired glucose homeostasis, and hypertension. The objective of this study was to determine whether this relationship is evident in HIV-infected individuals, who often exhibit changes in relative fat distribution, and to determine whether NC is independently associated with carotid intima-media thickness (cIMT) in HIV and non–HIV-infected patients.
RESEARCH DESIGN AND METHODS
Body composition, including anthropometrics, visceral adipose tissue assessment by CT, and metabolic parameters, including lipids, cIMT, and oral glucose tolerance test, were measured in 174 men and women with HIV infection and 154 non–HIV-infected subjects. NC was measured in triplicate inferior to the laryngeal prominence.
In univariate analysis, NC was significantly and positively related to blood pressure, hemoglobin A1c, glucose, and insulin and significantly and negatively related to HDL cholesterol in HIV-infected individuals and HIV-negative control subjects. NC was significantly associated with cIMT in univariate regression analysis among HIV-infected (r = 0.21, P = 0.006) and non–HIV-infected (r = 0.31, P = 0.0001) patients. This relationship remained significant among non–HIV-infected patients (R2 = 0.45, P < 0.001) but not HIV-infected patients in multivariate modeling controlling for age, sex, race, smoking hypertension, glucose, and lipids.
Among both HIV and non–HIV-infected patients, increased NC is strongly associated with decreased HDL and impaired glucose homeostasis. Among non–HIV-infected subjects, NC also predicts increased cIMT when controlling for traditional risk factors.
Carotid intima-media thickness (cIMT) reflects early atherosclerosis and predicts cardiovascular events in the general population. An increased cIMT is present in patients with rheumatoid arthritis, compared with control individuals, from the early stages of the disease and is thought to indicate accelerated atherosclerosis, but direct evidence is not available. Whether cIMT is susceptible to rapid and potentially reversible change depending on the intensity of inflammation in states of high-grade systemic inflammation, such as rheumatoid arthritis, remains unknown. If this is the case, an increased cIMT in such disease states may not reflect structural vessel wall damage, and may not be a good predictor of future cardiovascular events in these particular populations. Prospective, long-term, longitudinal studies are needed to address these questions.
Diabetes is associated with atherogenic risk factors. Hypertension has a major influence on cardiovascular disease in diabetic patients. Ambulatory blood pressure monitoring (ABPM) is useful for identifying nocturnal hypertension. Carotid intima-media thickness (cIMT) is a good measure for identifying subclinical atherosclerosis. This study aimed to evaluate whether nocturnal hypertension affects atherosclerosis in children and adolescents with type 1 diabetes and to investigate the relationship between atherogenic risk factors and cIMT.
RESEARCH DESIGN AND METHODS
ABPM and cIMT were measured in 82 diabetic children and adolescents. We reviewed the hemoglobin A1c levels, 24-h urine microalbumin excretion, lipid profiles, and duration of diabetes. Nocturnal hypertension was defined as hypertension observed only at night.
Forty-three (52%) subjects were hypertensive, and 30 subjects were classified as having nocturnal hypertension. cIMT was higher in the nocturnal hypertensive group than in the normotensive group (0.44 ± 0.03 vs. 0.42 ± 0.04 mm, P = 0.026). Among children and adolescents with nonhypertensive blood pressure levels in clinic blood pressure monitoring, cIMT and daytime blood pressure were higher in the nocturnal hypertensive group. All ABPM parameters were significantly related to cIMT in multiple linear regression analysis.
This study showed significantly increased cIMT and daytime blood pressure in diabetic children and adolescents with nocturnal hypertension. ABPM may be a useful method for detecting the macrovascular complications of type 1 diabetes. Longitudinal studies are needed to find the causes of nocturnal hypertension and to evaluate the effect of nocturnal hypertension on atherosclerosis in type 1 diabetes.