Carotid Artery Intima-media Thickness Progression Research Articles

Abstract WMP108: Association of Circulating Markers of Inflammation to Baseline and Progression of Carotid Artery Intima-Media Thickness

Introduction: There is strong evidence of an association between systemic inflammation and ischemic stroke. While the exact mechanism underpinning that association is unclear, there is evidence that systemic inflammation contributes to atherosclerosis progression. One measure of subclinical atherosclerosis, carotid artery intima-media thickness (CIMT), is independently associated with ischemic stroke. Because of mixed data on the association between systemic inflammation and CIMT progression, we sought to evaluate this relationship in a prospective cohort study. Hypothesis: Baseline elevation in circulating markers of inflammation are associated with CIMT progression in the Framingham Heart Study cohort. Methods: Among participants with two carotid ultrasounds (n=2350) about 10 years apart, 2,269 had data available on circulating markers of inflammation. Multivariable linear regression was used to assess the association between circulating markers of inflammation with internal carotid artery (ICA) CIMT. Analyses were adjusted for age, sex, hypertension, diabetes, APOE4, and body mass index (BMI), and baseline IMT. Results: Participants with higher baseline levels of C-reactive protein (CRP), interleukin-6 (IL-6), intracellular adhesion molecule, p-selectin, lipoprotein-associated phospholipase A2 (LPa) activity, homocysteine, isoprostanes (ISO), and CD40 ligand had significantly higher rates of ICA IMT progression adjusting for age, sex, hypertension, diabetes, APOE4, BMI, and baseline ICA IMT (Table). Participants with higher levels of CRP, IL-6, OPG, p-selectin, LPa activity, and ISO had greater follow-up ICA IMT adjusting for age, sex, hypertension, diabetes, APOE4, and BMI. Conclusion: Specific markers of inflammation are associated with increased later life carotid intima media thickening and carotid atherosclerosis progression, supporting a link between systemic inflammation and cerebrovascular disease.

Subclinical Atherosclerosis Across the Menopausal Transition in Women With and Without HIV.

The menopausal transition is a pivotal time of cardiovascular risk, but knowledge is limited in HIV. We studied longitudinal carotid artery intima-media thickness (CIMT) in the Women's Interagency HIV Study (2004-2019; 979 women/3247 person-visits; 72% with HIV). Among women with HIV only, those who transitioned had greater age-related CIMT progression compared to those remaining premenopausal (difference in slope = 1.64 µm/year, P = .002); and CIMT increased over time in the pretransition (3.47 µm/year, P = .002) and during the menopausal transition (9.41 µm/year, P < .0001), but not posttransition (2.9 µm/year, P = .19). In women with HIV, menopause may accelerate subclinical atherosclerosis as measured by CIMT.

Menopausal Hormone Therapy and Subclinical Cardiovascular Disease in Women With and Without Human Immunodeficiency Virus.

Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with human immunodeficiency virus (HIV), who have heightened immune activation and cardiovascular risks. Among 609 postmenopausal women (1234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis: carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors. Women (mean age, 51 years; 80% HIV positive) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never-users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio, 0.57 [95% confidence interval {CI}, .40-.80]; P < .01), 2.51 µm less progression of CIMT per year (95% CI, -4.60, to -.41; P = .02), and marginally lower incidence of plaque over approximately 7 years (risk ratio, 0.38 [95% CI, .14-1.03; P = .06), compared with never-users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment. HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low.

Childhood traffic-related air pollution and adverse changes in subclinical atherosclerosis measures from childhood to adulthood

BackgroundChronic exposure to air pollutants is associated with increased risk of cardiovascular disease (CVD) among adults. However, little is known about how air pollution may affect the development of subclinical atherosclerosis in younger populations. Carotid artery intima-media thickness (CIMT) is a measure of subclinical atherosclerosis that provides insight into early CVD pathogenesis.MethodsIn a pilot study of 70 participants from the Southern California Children’s Health Study, we investigated CIMT progression from childhood to adulthood. Using carotid artery ultrasound images obtained at age 10 and follow-up images at age 21–22, we examined associations between childhood ambient and traffic-related air pollutants with changes in CIMT over time and attained adult CIMT using linear mixed-effects models adjusted for potential confounders.Average residential childhood exposures (i.e., birth to time of measurement at 10–11 years) were assigned for regional, ambient pollutants (ozone, nitrogen dioxide, particulate matter, interpolated from regulatory air monitoring data) and traffic-related nitrogen oxides (NOx) by road class (modeled using the CALINE4 line source dispersion model). Traffic density was calculated within a 300-m residential buffer.ResultsFor each 1 standard deviation (SD) increase in childhood traffic-related total NOx exposure, we observed greater yearly rate of change in CIMT from childhood to adulthood (β: 2.17 μm/yr, 95% CI: 0.78–3.56). Increases in annual rate of CIMT change from childhood to adulthood also were observed with freeway NOx exposure (β: 2.24 μm/yr, 95% CI: 0.84–3.63) and traffic density (β: 2.11 μm/yr, 95% CI: 0.79–3.43). Traffic exposures were also related to increases in attained CIMT in early adulthood. No associations of CIMT change or attained level were observed with ambient pollutants.ConclusionsOverall, we observed adverse changes in CIMT over time in relation to childhood traffic-related NOx exposure and traffic density in our study population. While these results must be cautiously interpreted given the limited sample size, the observed associations of traffic measures with CIMT suggest a need for future studies to more fully explore this relationship.

Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes

BackgroundWe have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over 2 years (continuous care intervention, CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT).MethodsAnalyses were performed in patients with T2D who completed 2 years of this study (CCI; n = 194; usual care (UC): n = 68). Lipoprotein subfraction particle concentrations were measured by ion mobility at baseline, 1, and 2 years and CIMT was measured at baseline and 2 years. Principal component analysis (PCA) was used to assess changes in independent clusters of lipoprotein particles.ResultsAt 2 years, CCI resulted in a 23% decrease of small LDL IIIb and a 29% increase of large LDL I with no change in total LDL particle concentration or ApoB. The change in proportion of smaller and larger LDL was reflected by reversal of the small LDL subclass phenotype B in a high proportion of CCI participants (48.1%) and a shift in the principal component (PC) representing the atherogenic lipoprotein phenotype characteristic of T2D from a major to a secondary component of the total variance. The increase in LDL-C in the CCI group was mainly attributed to larger cholesterol-enriched LDL particles. CIMT showed no change in either the CCI or UC group.ConclusionConsumption of a very low carbohydrate diet with nutritional ketosis for 2 years in patients with type 2 diabetes lowered levels of small LDL particles that are commonly increased in diabetic dyslipidemia and are a marker for heightened CVD risk. A corresponding increase in concentrations of larger LDL particles was responsible for higher levels of plasma LDL-C. The lack of increase in total LDL particles, ApoB, and in progression of CIMT, provide supporting evidence that this dietary intervention did not adversely affect risk of CVD.

Association of Viral Persistence and Atherosclerosis in Adults With Treated HIV Infection

Persons living with HIV (PLWH) have increased risk for cardiovascular disease, and inflammation is thought to contribute to this excess risk. Production of HIV during otherwise effective antiretroviral therapy (ART) has been associated with inflammation. To determine whether higher levels of viral persistence are associated with atherosclerosis as assessed by changes in carotid artery intima-media thickness (IMT) over time. In this cohort study, intima-media thickness, a validated marker of atherosclerosis, was assessed over time in a cohort of treated PLWH with viral suppression. Cell-associated HIV DNA and RNA and change in IMT, adjusted for demographics, cardiovascular risk factors, and HIV-related factors, were examined, as well as which factors were associated with viral persistence. One hundred fifty-two PLWH with undetectable viral loads for at least 6 months before study enrollment were recruited from HIV clinics affiliated with 2 hospitals in San Francisco, California, from January 1, 2003, to December 31, 2012. Data were analyzed from February 7, 2018, to May 12, 2020. Cell-associated HIV RNA and DNA were measured using enriched CD4+ T cells from cryopreserved peripheral blood mononuclear cells. Carotid IMT was measured at baseline and the last visit, with a mean (SD) follow-up of 4.2 (2.7) years, using high-resolution B mode ultrasonography. The main study outcomes were baseline IMT, annual IMT progression, and incident plaque, defined as a focal region of carotid IMT of greater than 1.5 mm. The analysis included 152 PLWH (140 [92.1%] male; median age, 48.5 [interquartile range {IQR}, 43.3-53.7] years). Older age, smoking, medications for hypertension, higher low-density lipoprotein levels, and higher interleukin 6 levels were associated with higher baseline mean IMT, whereas cell-associated HIV DNA (estimate, -0.07% [95% CI, -6.1% to 6.4%]; P = .98), and HIV RNA levels (estimate, -0.8% [95% CI, -5.9% to 4.4%]; P = .75) were not. Levels of HIV RNA (0.017 [95% CI, 0.000-0.034] mm/y; P = .047) and HIV DNA (0.022 [95% CI, 0.001-0.044] mm/y; P = .042) were significantly associated with annual carotid artery IMT progression in unadjusted models only. Both HIV RNA (incidence risk ratio [IRR], 3.05 [95% CI, 1.49-6.27] per IQR; P = .002) and HIV DNA (IRR, 3.15 [95% CI, 1.51-6.57] per IQR; P = .002) were significantly associated with incident plaque, which remained significant after adjusting for demographics, cardiovascular risk factors, and HIV-related factors (IRR for HIV RNA, 4.05 [95% CI, 1.44-11.36] per IQR [P = .008]; IRR for HIV DNA, 3.35 [95% CI, 1.22-9.19] per IQR [P = .02]). Higher C-reactive protein levels were associated with higher cell-associated HIV RNA (estimate, 20.7% [95% CI, 0.9%-44.4%] per doubling; P = .04), whereas higher soluble CD14 levels were associated with HIV DNA (estimate, 18.6% [95% CI, 3.5%-35.8%] per 10% increase; P = .01). Higher soluble CD163 levels were associated with a higher HIV RNA:DNA ratio (difference, 63.8% [95% CI, 3.5%-159.4%]; P = .04). These findings suggest that measurements of viral persistence in treated HIV disease are independently associated with incident carotid plaque development. The size and transcriptional activity of the HIV reservoir may be important contributors to HIV-associated atherosclerosis.

Abstract P243: Impact of Menopausal Hormone Therapy on Association Between Heart Fat and Carotid Artery Atherosclerosis Progression in Recently Postmenopausal Women: the KEEPS Trial

Objective: Heart fat depots, within [epicardial adipose tissue (EAT)] and outside [paracardial adipose tissue (PAT)] the pericardium, have been linked to carotid atherosclerosis in various populations. Postmenopausal women have greater volumes of heart fat than premenopausal women. Our previous work suggests that lower endogenous estrogen may contribute to heart fat accumulation, although possibly limited to PAT, while postmenopausal oral hormone therapy (HT) may slow its progression. We evaluated the effect modification of HT use over 48 months on associations between heart fat accumulation and carotid artery intima-media thickness (CIMT) progression in recently postmenopausal women. Methods: The Kronos Early Estrogen Prevention Study (KEEPS) was a multi-center, randomized, double-blind placebo-controlled trial to investigate effects over 48 months of oral conjugated equine estrogens (o-CEE) and transdermal 17β-estradiol (t-E2), both given with cyclic progesterone, compared to placebo, on progression of CIMT in recently postmenopausal women. EAT and PAT volumes, and CIMT were measured at baseline and at 48 months. Associations between the absolute changes in heart fat volumes and CIMT as well as effect modification by HT type were tested using linear regression, adjusting for age, race, study site, employment status, diastolic and systolic blood pressure, anti-hypertensive medications, insulin resistance index, lipids, body-mass index, smoking, alcohol consumption, C-reactive protein, and adipokines. Results: Of 727 randomly assigned women, 467 [mean age (SD): 52.7(2.5); 78.2% Caucasian] had heart fat volumes and CIMT measured at both time points. Overall, changes in EAT and PAT were not associated with CIMT progression; however, assigned treatment significantly modified the association between changes in PAT, but not EAT, and CIMT progression in unadjusted model, P=0.04. In o-CEE group, CIMT progression was 0.028mm (SE:0.01mm) lower, per 1 unit increase in log PAT, than in t-E2 group, P=0.01, and trended 0.017mm (SE:0.01mm) lower than in placebo group, P=0.09. Although adjusted analysis attenuated these findings (P-value for interaction 0.09), differences between o-CEE and t-E2 groups remained significant, P=0.03. Conclusion: HT use modified the association between PAT accumulation, but not EAT, and CIMT progression. Our results suggest a potential beneficial impact of o-CEE (but not transdermal E2) on the relationship between adverse changes in PAT and CIMT. The current findings support the notion that EAT and PAT are distinct fat depots and suggest a complex role of HT in the association between heart fat and CIMT progression in recently postmenopausal women.

Comparative effects of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on carotid artery intima-media thickness progression: a network meta-analysis

BackgroundCarotid artery intima-media thickness (cIMT) progression is a surrogate marker of atherosclerosis with a high predictive value for future CVD risk. This study evaluates the comparative efficacies of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on cIMT progression.MethodsWe conducted a network meta-analysis (NMA) to evaluate the relative efficacies of several drug classes in modifying cIMT progression. After a literature search in several electronic databases, studies were selected by following predetermined eligibility criteria. An inverse variance-heterogeneity model was used for NMA. Sensitivity analyses were performed to check the reliability of the overall NMA, and transitivity analyses were performed to examine the effects of modifiers on the NMA outcomes.ResultsData were taken from 47 studies (15,721 patients; age: 60.2 years [95% confidence interval (CI) 58.8, 61.6]; BMI: 27.2 kg/m2 [95% CI 26.4, 28.0]; and gender: 58.3% males [95% CI 48.3, 68.3]). Treatment duration was 25.8 months [95% CI 22.9, 28.7]. Of the 13 drug classes in the network, treatment with phosphodiesterase III inhibitors was the most effective in retarding annual mean cIMT against network placebo (weighted mean difference (WMD) − 0.059 mm [95% CI − 0.099, − 0.020) followed by the calcium channel blockers (WMD − 0.055 mm [95% CI − 0.099, 0.001]) and platelet adenosine diphosphate inhibitors (WMD − 0.033 mm [95% CI − 0.058, 0.008]). These 3 drug classes also attained the same positions when the NMA was conducted by using first-year changes in mean cIMT. In transitivity analyses, longer treatment duration, higher body mass index (BMI), and a higher baseline cIMT were found to be independently associated with a lesser reduction in annual mean cIMT. However, in a multivariate analysis with these 3 modifiers, none of these factors was significantly associated with annual change in mean cIMT. In the placebo group, age was inversely associated with annual change in mean cIMT independently.ConclusionPhosphodiesterase III inhibitors and calcium channel blockers are found more effective than other drug classes in retarding cIMT progression. Age, BMI, and baseline cIMT may have some impact on these outcomes.

Differential Effect of Plasma Estradiol on Subclinical Atherosclerosis Progression in Early vs Late Postmenopause

The Early vs Late Intervention Trial with Estradiol showed that hormone therapy (HT) reduced progression of atherosclerosis when initiated in early but not in late postmenopause. This posttrial analysis examined the association between plasma estradiol (E2) levels and atherosclerosis determined by rate of change in carotid artery intima-media thickness (CIMT) and tested whether this association is equally evident in early (<6 years) vs late (≥10 years) postmenopause. Randomized controlled trial stratified by time since menopause (ClinicalTrials.gov no. NCT00114517). Mixed-effects linear models tested the association of E2 levels with CIMT rate of change. Los Angeles, California. Healthy women in postmenopause. Oral E2 with/without cyclic vaginal progesterone. Plasma E2 levels and CIMT assessed every 6 months over an average of 4.8 years. Among 596 women in postmenopause, higher E2 level was inversely associated with CIMT progression in those in early postmenopause (P = 0.041) and positively associated with CIMT progression in those in late postmenopause (P = 0.006) (P for interaction <0.001). CIMT progression rates for the lowest vs highest quartile of E2 levels among women in early postmenopause were 8.5 and 7.2 μm/y, respectively , whereas among women in late postmenopause they were 9.8 and 11.7 μm/y, respectively. E2 levels were differentially associated with atherosclerosis progression according to timing of HT initiation. With higher E2 levels, CIMT progression rate was decreased among women in early postmenopause but increased among women in late postmenopause. These results support the timing hypothesis of HT initiation on cardiovascular benefit, with reduced atherosclerosis progression for initiation during early postmenopause.

Subclinical cardiovascular disease in patients starting contemporary protease inhibitors.

The aim of the study was to assess changes in and factors associated with anatomical [carotid artery intima-media thickness (CIMT)] and functional (arterial stiffness) markers of subclinical cardiovascular disease progression in antiretroviral-naïve patients starting triple combination antiretroviral therapy containing contemporary protease inhibitors. This was a planned substudy of the ATADAR (Metabolic Effects of Atazanavir/Ritonavir Versus Darunavir/Ritonavir in Combination With Tenofovir/Emtricitabine in naïve HIV-1 Infected Patients) clinical trial (ClinicalTrials.gov identifier NCT01274780). ATADAR is a multicentre, randomized, open-label clinical trial comparing the effects of ritonavir-boosted atazanavir and darunavir, both with tenofovir/emtricitabine, in antiretroviral-naïve HIV-infected patients. Common CIMT and aortic augmentation index (AIx@75) were measured at baseline and after 12 months of follow-up. Antiretroviral treatment, traditional cardiovascular risk factors and HIV-related factors were assessed as potential predictors of CIMT and Aix@75 changes using linear regression analysis. Thirty-three patients were included in this pilot study. While CIMT significantly increased in the pooled population [median (interquartile range (IQR)) 68 (-13, 128) μm; P = 0.0511], AIx@75 did not [median (IQR) 1 (-6, 5)%; P = 0.8964]. Patients on darunavir showed a trend to faster CIMT progression than those on atazanavir [median change (IQR) 117 (-2, 143) vs. -6 (-58, 89) μm, respectively; P = 0.0917]. However, after adjustment in the multivariate analysis, a higher baseline Framingham score was the only factor associated with CIMT progression (coefficient 16.02; 95% confidence interval -1.04, 33.08; P = 0.064). AIx@75 change was not associated with any baseline factor. CIMT was a more sensitive marker of subclinical vascular disease progression than arterial stiffness in antiretroviral-naïve patients starting antiretroviral therapy with contemporary protease inhibitors. Classical risk factors but not antiretroviral therapy were associated with faster CIMT progression.

Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol

BackgroundData suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested.MethodsA total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima–media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen.ResultsAfter a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P=0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum.ConclusionsOral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum. (Funded by the National Institute on Aging, National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.)

Treat-to-target therapy does not prevent excessive progression of carotid intima media thickness during the first year of therapy in early rheumatoid arthritis.

IntroductionThe aim of the study was to investigate the presence of subclinical atherosclerosis and predictors of change in carotid intima-media measures in early rheumatoid arthritis patients (eRA) as compared to chronic RA patients and patients without arthritis.Material and methodsFifty-five consecutive eRA patients were assessed at the time of diagnosis and after 1 year of therapy. Fifty-five sex- and age-matched chronic RA patients and 29 patients without inflammatory disease were used as controls. Carotid artery intima-media thickness (CIMT) and carotid plaques were measured at baseline and after follow-up. In eRA patients ultrasound assessment of hand joints was performed before and after treatment. Carotid artery intima-media thickness was assessed again after 2 years in 44 eRA patients.ResultsCarotid artery intima-media thickness progression after 1 year of therapy was higher in eRA patients compared to both control groups (p = 0.017) and correlated with symptoms duration (p = 0.017) and DMARD monotherapy (p = 0.015). Ultrasound progression of hand joint erosions was associated with longer symptoms duration (p = 0.006). After 2 years of observation CIMT progression was similar in all examined groups.ConclusionsWe observed rapid CIMT progression during the first year of RA therapy. Longer symptoms duration and less aggressive therapy were associated with CIMT increase.

Abstract 14789: 2013 ACC/AHA Cholesterol Guideline Undertreats HIV-infected Adults With Carotid Atherosclerosis by Ultrasound

Background: While HIV infection is associated with increased risk of ASCVD (atherosclerotic cardiovascular disease), it is unknown whether guidelines can identify HIV-infected adults who may benefit from statins. The purpose of our study was to compare the 2013 ACC/AHA and 2004 ATP III recommendations in a HIV population, and to evaluate associations with carotid artery intima-media thickness (CIMT) and plaque. Methods: We used ultrasound to measure CIMT at baseline and 3 years later in 352 HIV-infected adults with no ASCVD and not on statins. Plaque was defined as IMT &gt; 1.5 mm. We compared 2013 ACC/AHA and 2004 ATP III recommendations, and evaluated associations with CIMT and plaque. Results: At baseline, the median age was 43 (IQR 39-49), 85% were male, 74% were on antiretroviral medication, and 50% had plaque. At follow-up, the median IMT progression was 0.052 mm/yr, and 66% had plaque. The 2013 guideline was more likely to recommend statins compared with the 2004 guideline, both overall (26% vs. 14%, p&lt;.001), in those with plaque (32% vs. 17%, p=.0002), and in those without plaque (16% vs. 7%, p=.025). In unadjusted linear regression, the 2004 and 2013 risk score were strongly associated with CIMT (0.01 mm per 10% increase in risk, p&lt;.001) and with CIMT progression (0.01 mm/yr per 10% increase in risk, p&lt;.001). In multivariate analysis, older age, higher LDL-C, pack-years of smoking, and history of opportunistic infection were associated with baseline plaque. Conclusions: While the 2013 ACC/AHA guideline recommended statins to a greater number of HIV-infected adults compared to the 2004 ATP III guideline, both failed to recommend therapy in the majority of HIV-affected adults with carotid plaque. Both the 2004 and 2013 guidelines predicted higher levels of baseline CIMT and faster progression. HIV-specific guidelines that include detection of subclinical atherosclerosis may help to identify HIV-infected adults who are at increased ASCVD risk and may benefit from statins.

Age and sex differences in the effect of parental stroke on the progression of carotid intima-media thickness

Background and purposeParental stroke is a risk factor for stroke among the offspring. Carotid artery intima-media thickness (IMT) is a widely regarded surrogate marker for atherosclerosis and a predictive marker for stroke. This study examines whether parental stroke is associated with IMT progression. MethodsThis longitudinal study had two measures of IMT that were taken upon enrollment of the 521 subjects and after an average follow-up of 4.1 years. The rate of IMT progression was tested for associations with parental stroke and cardiovascular risk factors using ANCOVA models. Age and sex were also tested as effect modifiers. The subjects were allocated into the young or old group using the age of 55 years. ResultsParental history of stroke was significantly associated with progression of common carotid artery (CCA) IMT compared with no parental stroke history (13.52 vs. 10.43 μm/year, adjusted p = 0.035). The parental effect on IMT progression of the bifurcation and internal carotid artery was dependent on age group. Young subjects had faster progression, whereas older subjects with parental stroke had slower progression. There was a three-way interaction among sex, age, and parental stroke in CCA IMT progression, such that young women with parental stroke had a 69.7% faster progression than young women without parental stroke (15.58 vs. 9.18 μm/year). However, this difference was not found in young men or old subjects with and without parental stroke. ConclusionsParental stroke is associated with carotid artery IMT progression and is more obvious in the young, especially among women. The results emphasize the clinical significance of parental stroke risk on atherosclerosis in young women.

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

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

Occupational stress and subclinical atherosclerosis: a systematic review.

Stress is a common hazard in the work environment and is associated with multiple adverse health effects. The association between work-related stress (WRS) and cardiovascular disease has been established in a number of epidemiological studies. A systematic review was conducted according to the PRISMA statement of the English literature involving WRS and carotid artery intima media thickness (CIMT). Four cohorts and six cross-sectional studies of occupational stress and CIMT were identified. All cohorts and five of the cross-sectional studies reported a significant positive association, while one reported an inverse association of WRS and CIMT. The weight of the evidence that we were able to identify suggests that occupational stress results in an increased risk of atherosclerosis, assessed via CIMT. Studies that include longitudinal measures of stress and intermediate cardiac endpoints, with adequate accounting for confounders, are needed. Interventional studies should also be conducted to determine whether CIMT progression can be prevented with workplace stress reduction.

Effect of prior oophorectomy on changes in bone mineral density and carotid artery intima-media thickness in postmenopausal women

To determine the effect of prior oophorectomy in healthy postmenopausal women on the rate of loss of bone mineral density (BMD) and rate of increase in carotid artery intima-media thickness (CIMT). Secondary analysis from a randomized controlled trial. University-based research clinic. Two hundred twenty-two healthy postmenopausal women in the Greater Los Angeles area. Baseline and annual screening of BMD and assessment of CIMT every 6 months for a total of 3 years. Changes in BMD and CIMT during postmenopausal years. Among women who were menopausal for more than 10 years, the rate of CIMT progression was statistically significantly less in women with intact ovaries compared with those in women with prior oophorectomy. In women 5-10 years postmenopause, there was a trend toward a slower loss of BMD in those who retained their ovaries, and in women more than 10 years postmenopause there was significantly less BMD loss in those who retained their ovaries. As time from menopausal transition increases, retained ovaries are associated with a slower rate of bone loss and a slower rate of thickening of the carotid artery wall compared with rates in menopausal women with oophorectomy.

Letter by Wang et al Regarding Article, “Childhood Air Pollutant Exposure and Carotid Artery Intima–Media Thickness in Young Adults”

HomeCirculationVol. 127, No. 22Letter by Wang et al Regarding Article, “Childhood Air Pollutant Exposure and Carotid Artery Intima–Media Thickness in Young Adults” Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBLetter by Wang et al Regarding Article, “Childhood Air Pollutant Exposure and Carotid Artery Intima–Media Thickness in Young Adults” Xi-Mei Wang, PhD, Yue-Jin Yang, MD, PhD and Yong-Jian Wu, MD, PhD Xi-Mei WangXi-Mei Wang Department of Cardiology, State Key Laboratory of Cardiovascular DiseaseFuwai Hospital, National Centre for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, People’s Republic of China Search for more papers by this author , Yue-Jin YangYue-Jin Yang Department of Cardiology, State Key Laboratory of Cardiovascular DiseaseFuwai Hospital, National Centre for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, People’s Republic of China Search for more papers by this author and Yong-Jian WuYong-Jian Wu Department of Cardiology, State Key Laboratory of Cardiovascular DiseaseFuwai Hospital, National Centre for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, People’s Republic of China Search for more papers by this author Originally published4 Jun 2013https://doi.org/10.1161/CIRCULATIONAHA.112.141564Circulation. 2013;127:e658To the Editor:We read with great interest the recently published article by Breton et al1 regarding childhood air pollutant exposure and carotid artery intima–media thickness (CIMT) in young adults. The authors report that childhood exposure to O3 is a novel risk factor for CIMT in a healthy population of college students. Given the study’s findings, we acknowledge that exposure to O3 may play an important role in the development of CIMT. However, based on the data provided in this study, we think that the authors should consider additional clinically relevant information that might help make the conclusion more convincing. It is well known that the risk factors associated with atherogenesis later in life are already present and observable in college-aged young adults, such as dietary pattern composition, blood pressure (BP) status during adolescence period, abnormal glucose metabolism, and so on. Now we will introduce the problems existing in this article in detail. First, the study did not analyze the information about the participants’ diet corresponding to the elementary school years (separately for ages 0–5 and 6–12 years) and lifetime exposure (from birth to date of CIMT measurement). Of note, the evidence has shown that subtle differences in dietary pattern composition affect the process of subclinical atherosclerosis.2 And dietary saturated fat is positively associated with artery calcium, whereas fiber and whole-grain intake can reduce progression of CIMT. Second, BP status during adolescence period of the participants is not taken into account. Because elevated BP at adolescence and a relative increase in BP from adolescence to adulthood unfavorably affect CIMT,3 these data should not be ignored in the analysis. Third, the most important deficit, however, is the lack of information on glucose metabolism of the participants. Previous studies have indicated that impaired glucose regulation categories increased vascular disease risk, as indicated by carotid/femoral intima–media thickness.4 Furthermore, even if normal glucose tolerance subjects with a 1-h postload glucose ≥155 mg/dL also have an atherogenic effects which is similar to impaired glucose tolerance individuals.5 Therefore, if all the participants have oral glucose tolerance test, it will be helpful in identification of the subjects who are at increased risk for CIMT. Nevertheless, the above important issues, which may limit the power to conclude an effect of childhood air pollutant on CIMT, were not discussed in this article. Finally, we believe that the applicative value of the result will be more instructive in real-world settings if the above information has been adjusted.Xi-Mei Wang, PhDYue-Jin Yang, MD, PhDYong-Jian Wu, MD, PhDDepartment of Cardiology, State Key Laboratory of Cardiovascular DiseaseFuwai Hospital, National Centre for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, People’s Republic of ChinaDisclosuresNone.

Dysfunctional HDL and progression of atherosclerosis in HIV-1-infected and -uninfected adults

BackgroundHDL function rather than absolute level may be a more accurate indicator for risk of developing atherosclerosis. Dysfunctional HDL has increased redox activity and reduced antioxidant properties, but it is unknown whether abnormal HDL function is associated with progression of atherosclerosis in HIV-1-infected subjects.FindingsWe retrospectively measured serum HDL function in 91 subjects from a prospective 3-year study of carotid artery intima-media thickness (CIMT), which enrolled triads of risk factor-matched persons that were HIV-1-uninfected (n=36) or HIV-1+ with (n=29) or without (n=26) protease inhibitor (PI)-based therapy for ≥ 2 years. HDL function was assessed using a biochemical assay that measures the oxidation of dihydrorhodamine 123 (DHR oxidation rate, DOR), in which higher DOR readout corresponds to dysfunctional HDL phenotype.There were no significant associations between DOR and HIV-1 infection. In univariate analysis of 55 HIV-1-infected subjects, greater waist circumference and lower serum HDL were significantly associated with higher baseline levels of DOR (p=0.01). These subjects had significant increases in levels of DOR over time (3 years) that were associated with white race (p=0.03), higher nadir CD4 count (p<0.001), and lower baseline CIMT (p<0.001). Lower baseline HDL levels, but not function of HDL (p>0.1) (DOR), were significantly associated (p=0.02) with progression of CIMT.ConclusionIn a small matched cohort study of HIV-1-infected subjects who had a low cardiovascular risk profile, HDL function changed over time and was independently associated with anthropometric parameters of obesity but not with progression of CIMT.

Early Atherosclerosis in Rheumatoid Arthritis: A case Control Study

BACKGROUND: Atherosclerosis remains the major cause of death and premature disability in developed countries.&#x0D; OBJECTIVES: To assess the prevalence of early (accelerated) atherosclerosis in Rheumatoid Arthritis (RA) patients in the absence of traditional risk factors and influence of various other parameters on it.&#x0D; METHODS: The study was carried at a tertiary care university hospital in northern India (Kashmir) in year 2008-2009. Thirty nine patients in the age group of 25- 55 years with RA fulfilling the American College of Rheumatology (ACR) Modified criteria 1987 and a purposive sample of twenty healthy volunteers that served as controls were enrolled to judge any difference in the studied parameters. Subjects with other risk factors for atherosclerosis were excluded from the study. Disease Activity Score (DAS-28) was used to measure the disease activity. B-mode ultrasonography was used to measure carotid artery intima media thickness (CIMT) in both the groups.&#x0D; RESULTS: RA patients presented with elevated CIMT in the age group of 41-50 years (p = 0.665) whereas volunteers had such tendency in the 5th decade of life (p = 0.550). Duration of disease greater than 5 years also positively influenced the development of increased CIMT in the patient group (p 0.64).Patients in the RA group had a higher erythrocyte sedimentation rate (ESR) and mean CIMT as compared to the controls(p = 0.000). RA patients had lower hemoglobin concentration when compared to age and sex matched controls. Intergroup comparison in patients with normal and increased CIMT showed that increased BMI, elevated triglyceride (TG) concentration and raised ESR influenced the development of CIMT which on binary logistic regression showed that TG (p = 0.043) and BMI (p = 0.053) had influence in progression of CIMT.&#x0D; CONCLUSION: Rheumatoid Arthritis patients have definite evidence of early (accelerated) atherosclerosis due to inflammation even in this ethnic population. BMI and serum triglycerides even in normal range have noteworthy influence in acceleration of atherosclerosis in them. B-mode ultrasonography is simple, non-invasive, and one of the sensitive methods to detect earlier atherosclerotic changes in them. JMS 2012;15(2):106-110