Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans.

Atherosclerosis precedes the onset of clinical manifestations of cardiovascular diseases (CVDs). We used carotid intima-media thickness (cIMT) to investigate genetic susceptibility to atherosclerosis in 7894 unrelated adults (3963 women, 3931 men; 40 to 60 years) resident in four sub-Saharan African countries. cIMT was measured by ultrasound and genotyping was performed on the H3Africa SNP Array. Two new African-specific genome-wide significant loci for mean-max cIMT, SIRPA (p = 4.7E-08), and FBXL17 (p = 2.5E-08), were identified. Sex-stratified analysis revealed associations with one male-specific locus, SNX29 (p = 6.3E-09), and two female-specific loci, LARP6 (p = 2.4E-09) and PROK1 (p = 1.0E-08). We replicate previous cIMT associations with different lead SNPs in linkage disequilibrium with SNPs primarily identified in European populations. Our study find significant enrichment for genes involved in oestrogen response from female-specific signals. The genes identified show biological relevance to atherosclerosis and/or CVDs, sex-differences and transferability of signals from non-African studies.

Cardiovascular risk assessment and coronary artery calcification burden in asymptomatic patients in the initial years of hemodialysis.

The specific tool for cardiovascular risk assessment in hemodialysis population has not yet been proposed, despite high prevalence of cardiovascular morbidity, and mortality in clinically asymptomatic patients. Coronary artery calcium score (CACS), as a reliable predictor of future cardiovascular events, might be a valuable approach. We sought to evaluate coronary artery calcification burden and its association with clinical and laboratory parameters in asymptomatic patients who recently initiated hemodialysis. The cross-sectional study included 60 asymptomatic patients receiving chronic hemodialysis for no longer than 48 months. CACS was assessed by cardiac computed tomography. Intima-media thickness (IMT) of both common carotid and femoral arteries were measured using ultrasonography. The mean total CACS was 160.50 (443). Patients' age correlated significantly with CACS (σ = 0.367; P = 0.004), carotid (σ = 0.375; P = 0.004) and femoral IMT (σ = 0.323; P = 0.013). Patients with CACS = 0 were significantly younger than patients with CACS >400: 52.4 ± 7.91 vs. 63.88 ± 8.37 years old, respectively (P = 0.034). In patients receiving dialysis for longer than 24 months CACS, femoral and carotid IMT were higher than in those dialyzed for less than 24 months; however, none has reached significance. There was a significant positive correlation between CACS and right (σ = 0.312; P = 0.018) and left (σ = 0.521; P < 0.001) femoral IMT, while not with carotid. CACS showed significant negative correlation with the serum iron (σ = -0.351; P = 0.007). Calcification burden varies significantly in asymptomatic patients in early years of dialysis. It correlates with patients' age and tends to increase with dialysis vintage. Femoral IMT might be useful for cardiovascular risk stratification in asymptomatic patients who recently initiated hemodialysis.

Sleep Apnea is Associated With Accelerated Vascular Aging: Results From 2 European Community-Based Cohort Studies.

Background The mechanisms underlying the association between obstructive sleep apnea (OSA) and cardiovascular disease may include accelerated vascular aging. The aim was to compare the magnitude of vascular aging in patients with high versus low risk of OSA. Methods and Results In 2 community-based studies, the PPS3 (Paris Prospective Study 3) and the Maastricht Study, high risk of OSA was determined with the Berlin questionnaire (a screening questionnaire for OSA). We assessed carotid artery properties (carotid intima-media thickness, Young's elastic modulus, carotid-femoral pulse wave velocity, carotid pulse wave velocity, carotid diameter using high precision ultrasound echography), and carotid-femoral pulse wave velocity (in the Maastricht Study only). Regression coefficients were estimated on pooled data using multivariate linear regression. A total of 8615 participants without prior cardiovascular disease were included (6840 from PPS3, 62% men, mean age 59.5±6.2 years, and 1775 from the Maastricht Study, 51% men, 58.9±8.1 years). Overall, high risk of OSA prevalence was 16.8% (n=1150) in PPS3 and 23.8% (n=423) in the Maastricht Study. A high risk of OSA was associated with greater carotid intima-media thickness (ß=0.21; 0.17-0.26), Young's elastic modulus (ß=0.21; 0.17-0.25), carotid-femoral pulse wave velocity (ß=0.24; 0.14-0.34), carotid pulse wave velocity (ß=0.31; 0.26-0.35), and carotid diameter (ß=0.43; 0.38-0.48), after adjustment for age, sex, total cholesterol, smoking, education level, diabetes mellitus, heart rate, and study site. Consistent associations were observed after additional adjustments for mean blood pressure, body mass index, or antihypertensive medications. Conclusions These data lend support for accelerated vascular aging in individuals with high risk of OSA. This may, at least in part, underlie the association between OSA and cardiovascular disease.

Variants translating reduced expression of the beta estrogen receptor gene were associated with increased carotid intima media thickness: A cross-sectional study in late postmenopausal women.

ABSTRACT: There is debate on the role of estrogens in modulating the risk for atherosclerosis in women. Our purpose was to investigate whether the size of the estrogenic impact was independently associated with variation of carotid intima-media thickness (IMT) in healthy late postmenopausal women. The levels of circulating estrogens have been used in previous studies but the influence of SNPs of the estrogen receptors (ER) α and ß have not been investigated.We performed a crossed-sectional study of 91 women in a university hospital. We used a double approach in which, in addition to the measurement of estradiol levels by ultrasensitive methods, genetic variants (SNPs) associated with differing expression of the ER α and ß genes were assessed. Multivariable analysis was used to examine the association of candidate factors with the value of IMT and plaque detection at both the carotid wall and the sinus.A genotype combination translating reduced gene expression of the ERß was directly associated with IMT at both the carotid wall (P = .001) and the sinus (P = .002). Other predictors of IMT were the levels of glucose, positively associated with IMT at both the carotid wall (P < .001) and the sinus (P = .001), age positively associated with IMT at the sinus (P = .003), and levels of vitamin D, positively associated with IMT at the carotid wall (P = .04).Poorer estrogenic impact, as concordant with a SNP variant imposing reduced expression of the ERß, was directly associated with IMT at both the carotid wall and the sinus. Glucose level, vitamin D only for the carotid wall, and age only for the sinus, also emerged as independent factors in the IMT variance.

Association of breastfeeding duration with carotid intima-media thickness in later life: a systematic review and meta-analysis.

OBJECTIVE: To assess the relationship of breastfeeding duration with maternal ultrasound carotid intima-media thickness (CIMT) in later life. METHODS: PubMed, Scopus, Web of Science, Embase, and Cochrane Central database searching up to December 15, 2020, for eligible studies that reported on the breastfeeding duration and ultrasound measurement of CIMT in later life. The exposed group corresponded to breastfeeding duration ≥ 6 months whereas the control group was women with breastfeeding of shorter duration or nil breastfeeding. The methodological quality of reviewed articles was appraised using the Newcastle-Ottawa Scale (NOS). Results are reported as the mean difference (MD) or the standardized MD (SMD) and their 95% confidence intervals (CIs). The study was registered in the PROSPERO database. RESULTS: Of 532 unique studies, three studies met inclusion criteria including 1721 women with a mean age ranging between 36.6 ± 6.9 and 55.7 ± 5.3 years, comparing breastfeeding duration ≥ 6 months versus 1-5 months (NOS: 7-8). Common CIMT was lower in women who breastfed for a longer duration (SMD = -0.10, 95% CI -0.20 to -0.00). Circulating HDL-cholesterol was higher in women with longer breastfeeding duration (MD = 3.25, 95% CI 0.88-5.61). There were no significant differences for total cholesterol, LDL-cholesterol, triglycerides, glucose, and blood pressure between breastfeeding 6 or more months and the control group. CONCLUSIONS: The available studies showed lower CIMT and higher HDL-cholesterol levels in women who breastfed for 6 or more months as compared to controls.

Poor cardiovascular health is associated with subclinical atherosclerosis in apparently healthy sub-Saharan African populations: an H3Africa AWI-Gen study.

BACKGROUND: The cardiovascular health index (CVHI) introduced by the American Heart Association is a valid, accessible, simple, and translatable metric for monitoring cardiovascular health in a population. Components of the CVHI include the following seven cardiovascular risk factors (often captured as life's simple 7): smoking, dietary intake, physical activity, body mass index, blood pressure, glucose, and total cholesterol. We sought to expand the evidence for its utility to under-studied populations in sub-Saharan Africa, by determining its association with common carotid intima-media thickness (CIMT). METHODS: We conducted a cross-sectional study involving 9011 participants drawn from Burkina Faso, Ghana, Kenya, and South Africa. We assessed established classical cardiovascular risk factors and measured carotid intima-media thickness of the left and right common carotid arteries using B-mode ultrasonography. Adjusted multilevel mixed-effect linear regression was used to determine the association of CVHI with common CIMT. In the combined population, an individual participant data meta-analyses random-effects was used to conduct pooled comparative sub-group analyses for differences between countries, sex, and socio-economic status. RESULTS: The mean age of the study population was 51 ± 7 years and 51% were women, with a mean common CIMT of 637 ± 117 µm and CVHI score of 10.3 ± 2.0. Inverse associations were found between CVHI and common CIMT (ß-coefficients [95% confidence interval]: Burkina Faso, - 6.51 [- 9.83, - 3.20] µm; Ghana, - 5.42 [- 8.90, - 1.95]; Kenya, - 6.58 [- 9.05, - 4.10]; and South Africa, - 7.85 [- 9.65, - 6.05]). Inverse relations were observed for women (- 4.44 [- 6.23, - 2.65]) and men (- 6.27 [- 7.91, - 4.64]) in the pooled sample. Smoking (p < 0.001), physical activity (p < 0.001), and hyperglycemia (p < 0.001) were related to CIMT in women only, while blood pressure and obesity were related to CIMT in both women and men (p < 0.001). CONCLUSION: This large pan-African population study demonstrates that CVHI is a strong marker of subclinical atherosclerosis, measured by common CIMT and importantly demonstrates that primary prevention of atherosclerotic cardiovascular disease in this understudied population should target physical activity, smoking, obesity, hypertension, and hyperglycemia.

Baseline carotid intima-media thickness is associated with cardiovascular morbidity and mortality in peritoneal dialysis patients.

Carotid intima-media thickness (CIMT) is an early marker of atherosclerosis and is increased in peritoneal dialysis (PD) patients. Association of CIMT with cardiovascular disease (CVD) or mortality is less clear. Fibroblast growth factor-23 (FGF-23) is a hormone associated with vascular calcification, atherosclerosis, and mortality in the hemodialysis population. We investigated whether baseline CIMT and FGF-23 are associated with CVD and mortality in PD patients. Fifty-five PD patients were included. CVD was defined as ischemic heart disease, stroke, or peripheral artery disease. Intact FGF-23 was measured in plasma. CIMT was measured by ultrasonography. Twenty-one patients developed CVD and 12 died over 47.1 ± 33.8 months. Patients with CVD were older (55.9 ± 10.5 vs. 42.5 ± 12.9 years, P < .01), had lower albumin (3.8 ± 0.5 vs. 4.2 ± 0.3 g/dL, P < .01) and higher CIMT (0.87 ± 0.22 vs. 0.61 ± 0.11 mm, P < .01). Patients with mortality were also older (53.5 ± 11.5 vs. 45.8 ± 13.8 years, P = .05), had lower albumin (3.7 ± 0.6 vs. 4.1 ± 0.3 g/dL, P < .01), higher CRP (15.0 ± 8.5 vs. 7.6 ± 8.4 mg/L, P < .01) and CIMT (0.9 ± 0.3 vs. 0.6 ± 0.1 mm, P < .01). Albumin and CIMT were associated with CVD and CIMT > 0.75 mm was associated with cardiovascular mortality. FGF-23 did not show any correlations. CIMT at baseline is associated with CVD and mortality in PD patients.

Circulating Amyloid Beta 1-40 Is Associated with Increased Rate of Progression of Atherosclerosis in Menopause: A Prospective Cohort Study.

BACKGROUND: Accumulating evidence suggests that circulating amyloidß 1-40 (Αß1-40), a proatherogenic aging peptide, may serve as a novel biomarker in cardiovascular disease (CVD). We aimed to explore the role of plasma Αß1-40 and its patterns of change over time in atherosclerosis progression in postmenopausal women, a population with substantial unrecognized CVD risk beyond traditional risk factors (TRFs). METHODS: In this prospective study, Αß1-40 was measured in plasma by enzyme-linked immunosorbent assay and atherosclerosis was assessed using carotid high-resolution ultrasonography at baseline and after a median follow-up of 28.2 months in 152 postmenopausal women without history or symptoms of CVD. RESULTS: At baseline, high Αß1-40 was independently associated with higher carotid bulb intima-media thickness (cbIMT) and the sum of maximal wall thickness in all carotid sites (sumWT) (p < 0.05). Αß1-40 levels increased over time and were associated with decreasing renal function (p < 0.05 for both). Women with a pattern of increasing or persistently high Αß1-40 levels presented accelerated progression of cbIMT and maximum carotid wall thickness and sumWT (p < 0.05 for all) after adjustment for baseline Αß1-40 levels, TRFs, and renal function. CONCLUSION: In postmenopausal women, a pattern of increasing or persistently high Αß1-40 was associated with the rate of progression of subclinical atherosclerosis irrespective of its baseline levels. These findings provide novel insights into a link between Αß1-40 and atherosclerosis progression in menopause and warrant further research to clarify the clinical value of monitoring its circulating levels as an atherosclerosis biomarker in women without clinically overt CVD.

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

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Exposures: Cell-associated HIV RNA and DNA were measured using enriched CD4+ T cells from cryopreserved peripheral blood mononuclear cells. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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.

Association of Visceral Adipose Tissue and Subclinical Atherosclerosis in US-Born Mexican Americans but not First Generation Immigrants.

Background Excess visceral adipose tissue (VAT) is a primary driver for the cardiometabolic complications of obesity; VAT-associated cardiovascular disease risk varies by race, but most studies have been done on Non-Hispanics. This study aimed to evaluate the clinical and metabolic correlates of VAT, its association with subclinical atherosclerosis, and the factors affecting this association in Mexican Americans. Methods and Results Participants (n=527) were drawn from the Cameron County Hispanic Cohort (CCHC), on whom a carotid ultrasound to assess carotid intima media thickness and a dual-energy X-ray absorptiometry scan to assess for VAT were obtained. Those in the highest quartiles of VAT were more likely to have hypertension, hypertriglyceridemia, low high-density lipoprotein, diabetes mellitus, and metabolic syndrome. Increased carotid intima media thickness was more prevalent in those in the highest quartile for VAT (57.4% versus 15.4% for the lowest quartile; P<0.001). There was a graded increase in mean carotid intima media thickness with increasing VAT, after adjusting for covariates; for every 10 cm2 increase in VAT, there was an increase of 0.004 mm (SE=0.002; P=0.0299) in mean carotid intima media thickness. However, this association was only seen among second or higher generation US-born Mexican Americans but not among first generation immigrants (P=0.024). Conclusions Excess VAT is associated with indicators of metabolic disorders and subclinical atherosclerosis in Mexican Americans regardless of body mass index. However, acculturation appears to be an important modulator of this association. Longitudinal follow-up with targeted interventions among second or higher generation Hispanics to lower VAT and improve cardiometabolic risk may help prevent premature cardiovascular disease in this cohort.

Magnesium Levels Modify the Effect of Lipid Parameters on Carotid Intima Media Thickness.

Classical risk factors of atherosclerosis in the general population show paradoxical effects in chronic kidney disease (CKD) patients. Thus, low low-density lipoprotein (LDL) cholesterol levels have been associated with worse cardiovascular outcomes. Magnesium (Mg) is a divalent cation whose homeostasis is altered in CKD. Furthermore, Mg levels have been associated with cardiovascular health. The present study aims to understand the relationships of Mg and lipid parameters with atherosclerosis in CKD. In this analysis, 1754 participants from the Observatorio Nacional de Atherosclerosis en Nefrologia (NEFRONA) cohort were included. Carotid intima media thickness (cIMT) was determined in six arterial territories, and associated factors were investigated by linear regression. cIMT correlated positively with being male, Caucasian, a smoker, diabetic, hypertensive, dyslipidemic and with increased age, BMI, and triglyceride levels, and negatively with levels of HDL cholesterol. First-order interactions in linear regression analysis showed that Mg was an effect modifier on the influence of lipidic parameters. Thus, cIMT predicted values were higher when triglycerides or LDL levels were high and Mg levels were low. On the contrary, when Mg levels were high, this effect disappeared. In conclusion, Mg acts as an effect modifier between lipidic parameters and atherosclerotic cardiovascular disease. Therefore, Mg levels, together with lipidic parameters, should be taken into account when assessing atherosclerotic risk.

Associations of Carotid Intima-Media Thickness and Plaque Heterogeneity With the Risks of Stroke Subtypes and Coronary Artery Disease in the Japanese General Population: The Circulatory Risk in Communities Study.

Background Evidence on the associations of carotid intima-media thickness and carotid plaque characteristics with stroke subtypes and coronary artery disease risks in Asians is limited. This study investigated these associations in the Japanese general population. Methods and Results Maximum intima-media thicknesses of both the common carotid artery and internal carotid artery and carotid plaque characteristics were evaluated in 2943 Japanese subjects aged 40 to 75 years without history of cardiovascular disease. Subjects were followed up for a median of 15.1 years. Using a multivariate Cox proportional hazard model, we found that hazard ratios (HRs) and 95% CIs for the highest (≥1.07 mm) versus lowest (≤0.77 mm) quartiles of maximum intima-media thicknesses of the common carotid artery were 1.97 (1.26-3.06) for total stroke, 1.52 (0.67-3.41) for hemorrhagic stroke, 2.45 (1.41-4.27) for ischemic stroke, 3.60 (1.64-7.91) for lacunar infarction, 1.53 (0.69-3.41) for nonlacunar cerebral infarction, 2.68 (1.24-5.76) for coronary artery disease, and 2.11 (1.44-3.12) for cardiovascular disease (similar results were found for maximum intima-media thicknesses of the internal carotid artery). HRs(95% CIs) for heterogeneous plaque versus no plaque were 1.58 (1.09-2.30) for total stroke, 1.25 (0.58-2.70) for hemorrhagic stroke, 1.74 (1.13-2.67) for ischemic stroke, 1.84 (1.03-3.19) for lacunar infarction, 1.58 (0.80-3.11) for nonlacunar cerebral infarction, 2.11 (1.20-3.70) for coronary artery disease, and 1.71 (1.25-2.35) for cardiovascular disease. Conclusions Maximum intima-media thicknesses of the common carotid artery, maximum intima-media thicknesses of the internal carotid artery, and heterogeneous plaque were associated with the risks of stroke, lacunar infarction, coronary artery disease, and cardiovascular disease in Asians.

Carotid Intima-Media Thickness and the Risk of Sudden Cardiac Death: The ARIC Study and the CHS.

Background Sudden cardiac death (SCD) is associated with severe coronary heart disease in the great majority of cases. Whether carotid intima-media thickness (C-IMT), a known surrogate marker of subclinical atherosclerosis, is associated with risk of SCD in a general population remains unknown. The objective of this study was to investigate the association between C-IMT and risk of SCD. Methods and Results We examined a total of 20 862 participants: 15 307 participants of the ARIC (Atherosclerosis Risk in Communities) study and 5555 participants of the CHS (Cardiovascular Health Study). C-IMT and common carotid artery intima-media thickness was measured at baseline by ultrasound. Presence of plaque was judged by trained readers. Over a median of 23.5 years of follow-up, 569 participants had SCD (1.81 cases per 1000 person-years) in the ARIC study. Mean C-IMT and common carotid artery intima-media thickness were associated with risk of SCD after adjustment for traditional risk factors and time-varying adjustors: hazard ratios (HRs) with 95% CIs for fourth versus first quartile were 1.64 (1.15-2.63) and 1.49 (1.05-2.11), respectively. In CHS, 302 participants developed SCD (4.64 cases per 1000 person-years) over 13.1 years. Maximum C-IMT was associated with risk of SCD after adjustment: HR (95% CI) for fourth versus first quartile was 1.75 (1.22-2.51). Presence of plaque was associated with 35% increased risk of SCD: HR (95% CI) of 1.37 (1.13-1.67) in the ARIC study and 1.32 (1.04-1.68) in CHS. Conclusions C-IMT was associated with risk of SCD in 2 biracial community-based cohorts. C-IMT may be used as a marker of SCD risk and potentially to initiate early therapeutic interventions to mitigate the risk.

Subclinical atherosclerosis in systemic sclerosis and rheumatoid arthritis: a comparative matched-cohort study.

Systemic autoimmune inflammatory disorders confer a higher risk of cardiovascular (CV) disease leading to increased morbidity and mortality and reduced life expectancy compared to the general population. CV risk in systemic sclerosis (SSc) has not been studied extensively but surrogate markers of atherosclerosis namely carotid intima media thickness (cIMT) and pulse wave velocity (PWV) are impaired in some but not all studies in SSc patients. The aim of this study was to investigate the prevalence of subclinical atherosclerosis assessed by cIMT and PWV between two well-characterized SSc and Rheumatoid Arthritis (RA) cohorts. Consecutive SSc patients attending the Scleroderma Clinic were compared with RA patients recruited in the Dudley Rheumatoid Arthritis Co-morbidity Cohort (DRACCO), a prospective study examining CV burden in RA. Augmentation Index (Aix75) and cIMT were measured in all participants. Propensity score matching was utilised to select patients from the two cohorts with similar demographic characteristics, CV risk factors and inflammatory load. Unpaired analysis was performed using unpaired t test for continuous variables and χ2 test for dichotomous variables. Statistical analysis was repeated using paired t test for continuous normal variables and McNemar's test for dichotomous variables. Fifty five age- and sex-matched SSc and RA patients were included in the analysis. No difference was demonstrated between SSc and RA subjects regarding cIMT (0.66 mm vs 0.63 mm, respectively) and Aix75% measurements (33.4 vs 31.7, respectively) neither in paired (p = 0.623 for cIMT and p = 0.204 for Aix%) nor in unpaired t test analysis (p = 0.137 for cIMT and p = 0.397 for AIx%). The results of this comparative study show that subclinical atherosclerosis is comparable between SSc and RA, a systemic disease with well-defined high atherosclerotic burden. Such findings underscore the importance of CV risk management in SSc in parallel with other disease-related manifestations.

Plasma Homocysteine in Patients with Coronary and Carotid Artery Disease: A Case Control Study.

INTRODUCTION: Homocystein (Hcy) is an amino acid and elevated plasma cause endothelial damage, followed with inflammation in the blood vessels and its progression in atherosclerosis. We aimed to evaluate the correlation between cardiovascular disease and serum homocysteine levels.. METHODS: We performed a case control analysis of 212 patients, either for cardiovascular risk stratification or for invasive diagnostics and treatment of cardiovascular ischemic disease (CAD). Patients were divided into 4 groups: Group 1. Patients with low risk for CAD, with no symptoms of CAD and total of 10 years risk <10%. Group 2. High-risk patients with no symptoms of CAD, but 10 years total CAD risk of >20%. Group 3. Patients with symptomatic CAD, where angiography was performed and >50% occlusion of at least one coronary vessel was found. Group 4. Patients with carotid artery disease and documented CAD. RESULTS: Group 1 consists of 56 subjects, of whom 33 (60%) males and 22 (40%) females. Their mean age was 52.18±8.07 years and their average CAD risk was 5. Group 2 included 60 patients, with average CAD risk of 23.73. There was a statistically significant difference between plasma homocysteine levels between the control and high CAD risk group, as well as between those with CAD and both CAD and CARD (p=0.001). In the high-risk subjects group, the level of homocysteine correlates albeit weak with the total CAD risk (p=0.04). Homocysteine levels correlate with the WBC count (p=0.02). In the subgroup of smokers with high CAD risk, homocysteine correlates with age, total CAD risk, total cholesterol, BUN (define BUN) and creatinine. Group 3 consisted of 49 subjects with manifested and angiographically proven CAD, out of whom 80% were males and 20% females, mean age 56.06±9.7 years, with average 2 coronary vessels affected. There were significantly higher homocysteine plasma levels between the control group and the group with manifested CAD (p=0.008).There is no significant difference of homocysteine plasma levels between the high risk group and the group with manifested coronary artery disease (15.03□mol/l vs. 16.38□mol/l). In this group, plasma levels of homocysteine correlate only with the highest level of vessel stenosis (>95%) with (p=0.04). The study population in group 4 showed a mean of IMT 0.9 +..09 mm and mean Hcy plasma levels of 21 + 11 µmol/L. From the evaluated patients with CAD, 82.9% of patients had elevated level of Hcy. From those, one showed elevated Hcy, 79.4 % had hypertension, 58.9 % had hyperlipidemia, 28.2% had diabetes mellitus as additional risk factors for atherosclerosis. 76.9 % of the patients had increased intima-media thickness; in 58.9 % plaques were detected, while 23 % of the patients had significant stenosis: 10.2 % with intermediate-grade stenosis (50-69%) and 12.8 % with high-grade stenosis (70-99 %). 17.1 % of the patients had normal level of Hcy, and in those ones 62.5 % only had increased IMT. We found linear correlation between IMT and HCy levels (r 0.7, p 0.05). Case control analysis showed significant higher level of Hcy in the group with CAD and carotid artery disease vs. CAD group (p 0.001). CONCLUSION: High plasma homocysteine concentrations are associated with high risk for vascular disease and consequently CAD itself and carotid artery disease, as well, proving its likely role in the development of atherosclerosis on inflammatory and metabolic levels.

Increased carotid stiffness detected by ultrafast ultrasound imaging is associated with the Gensini score.

AIM: To test the ability of carotid stiffness evaluated by using ultrafast ultrasound imaging to indicate coronary atherosclerosis and its association with the severity of coronary artery disease (CAD). MATERIAL AND METHODS: This cross-sectional study included 131 patients with CAD and 60 normal controls. Carotid intima-media thickness (cIMT) was measured by two-dimensional ultrasound. Carotid stiffness was determined by ultrafast ultrasound imaging, with which the carotid pulse wave velocity at the beginning (PWVBS) and end (PWVES) of systole were calculated. Gensini scores based on coronary angiography were used to estimate the severity of CAD. RESULTS: Compared with normal controls, the CAD patients had higher carotid diameters, cIMT, PWVBS and PWVES (p < 0.05). In the CAD group, Gensini scores correlated significantly with cIMT, PWVBS and PWVES (r = 0.279, p = 0.001; r = 0.661, p < 0.001; r = 0.620, p < 0.001; respectively). The multivariate analysis further indicated that PWVBS, PWVES and body mass index were independently associated with the Gensini score (ß = 0.466, p < 0.001; ß = 0.308, p < 0.001; and ß = 0.209, p = 0.001; respectively). In addition, the sensitivity and specificity were 54% and 83%, respectively, for PWVBS (cutoff value, 6.9 m/s; area under the receiver operating characteristic curve, 0.70) and 64% and 83%, respectively, for PWVES (cutoff value, 8.0 m/s; area under the curve, 0.73). CONCLUSIONS: Increased carotid PWVBS and PWVES detected by ultrafast ultrasound imaging as indices of carotid stiffness might serve as promising indicators for CAD and its severity.

Risk factors of subclinical atherosclerosis in obesity and overweight.

OBJECTIVE: To examine the relationship of carotid intima-media thickness with weight-gain, overweight and obesity.. METHODS: The experimental, analytical study was conducted at the CF University Hospital, Cluj-Napoca, Romania, from 2012 to 2014, and comprised randomly selected in patients from the Medical Ward. The patients were divided into normal-weight subjects in Group I and overweight and obese subjects in Group II Intimate-media thickness was measured by carotid Doppler ultrasound. Data was analysed using SPSS 13. RESULTS: Of the 111 subjects, Group I had 27(%) and Group II had 84(%) subjects. Mean carotid intimamedia thickness was significantly greater (p<0.001) in Group II compared to Group I, especially in those with metabolic syndrome (p<0.001) and higher high-sensitivity C reactive protein (p<0.05). With the exception of Group II where there was a direct correlation (p<0.05) between triglycerides and intimamedia thickness, and an inverse correlation (p<0.05) between high-density lipoprotein and intimamedia thickness, no significant correlations were recorded (p>0.05). CONCLUSIONS: Intima-media thickness was found to be increased in asymptomatic overweight and obese subjects, significantly higher in those with associated metabolic syndrome and high levels of highsensitivity C-reactive protein, as an indication of the presence of early, subclinical atherosclerosis.

Sex-based impact of carotid plaque in patients with chest pain undergoing stress echocardiography.

OBJECTIVE: Women with suspected angina without history of coronary artery disease (CAD) less frequently have flow-limiting stenosis (FL-CAD) and more often have microvascular disease, affecting predictive accuracy of stress echocardiography (SE) for detection of FL-CAD. We postulated that carotid plaque burden (CPB) assessment would improve detection of FL-CAD and risk stratification. METHODS: Consecutive consenting patients assessed by SE on clinical grounds for new-onset chest pain also underwent simultaneous carotid ultrasound. Patients were followed for major adverse events (MAE): all-cause mortality, non-fatal myocardial infarction and unplanned revascularisation. Carotid plaque presence and burden (CPB) were assessed. RESULTS: After a mean of 2617±469 days (range 17-3740), of 591 recruited patients, 573 (97%) outcome data (314 females) were obtainable. Despite lower pretest probability of CAD in females versus males (14.9±0.8 vs 20.5±1.3, respectively, p<0.0001), prevalence of myocardial ischaemia was similar (p=0.08). Females also had lower prevalence of both carotid plaque (p<0.0001) and FL-CAD (p<0.05). CPB improved the positive predictive value of SE for detection of FL-CAD (from 34.5% to 60%) in females but not in males. Absence of CPB in females with myocardial ischaemia ruled out FL-CAD in 93% versus 57% in males. CPB was the only independent predictor of MAE (p=0.012) in females, whereas in males both SE (p<0.0001) and CPB (p=0.003) remained significant. CONCLUSION: In females with new-onset stable angina without a history of cardiovascular disease, CPB improved the predictive accuracy of myocardial ischaemia for flow-limiting CAD. However, CPB provided incremental risk stratification in both sexes.

Inverse Relationship between Plasma Tumor Necrosis Factor-Like Weak Inducer of Apoptosis and Carotid Intima-Media Thickness among Patients Undergoing Hemodialysis and Peritoneal Dialysis.

BACKGROUND/AIMS: This study aimed to investigate the level of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and its correlation with micro-inflammation and atherosclerosis in continuous ambulatory peritoneal dialysis (PD) patients. METHODS: This retrospective study involved 23 healthy subjects (control group), 23 hemodialysis (HD) patients (HD group) and 26 PD patients (PD group). Serum biochemical measurements and sTWEAK assessments were tested. The association between intima-media thickness (IMT) and sTWEAK concentrations was evaluated. RESULTS: The TWEAK level was lower in PD (155.16 ± 3.69 pg/mL, p < 0.001) and the HD group (150.16 ± 7.23 pg/mL, p < 0.001) than that in the control group (193.05 ± 5.36 pg/mL), with no significant difference between the PD group and the HD group. In the PD and HD groups, sTWEAK was significant negatively correlated with CPR, fibrinogen, and white blood cell (p < 0.05). Besides, compared to lower sTWEAK concentration end-stage renal disease (ESRD) patients (no >161.9 pg/mL), patients who had a higher level of sTWEAK (>161.9 pg/mL) had a lower IMT (0.97 ± 0.04 vs. 0.84 ± 0.03 cm, p = 0.029). After adjusted for sex, age, hypertension, diabetes, duration of dialysis, triglyceride, total cholesterol, low-density lipoprotein, and serum glucose, sTWEAK (B = -0.002, r = 0.015) and CRP (B = 0.022, r = 0.015) were independent risk factors for the IMT of ESRD patients. CONCLUSION: Plasma TWEAK is inversely associated with carotid IMT among patients undergoing HD and PD.

Similar progression of carotid intima-media thickness in 7-year surveillance of patients with mild SLE and controls, but this progression is still promoted by dyslipidaemia, lower HDL levels, hypertension, history of lupus nephritis and a higher prednisolone usage in patients.

Objective: To compare progression of subclinical atherosclerosis and factors promoting it in patients with SLE and controls. Methods: Consecutive patients with SLE and age-matched, sex-matched population controls from the SLEVIC cohort were assessed at inclusion and after 7 years with standardised data collection and carotid ultrasound. Effect of risk factors on carotid intima-media thickness (cIMT) progression was examined with adjusted linear mixed models. Results: A total of 77 patients and 74 controls, 68% and 61% of the original cohort, completed follow-up. The patients were (mean) 47 years old, 90% were women, and controls were 51 years old, 92% women. Patients had disease duration of (mean) 11 years, mild disease activity and low severity at both assessments. Baseline cIMT did not differ between the groups. An average absolute cIMT progression was 0.009 mm/year in patients and 0.011 mm/year in controls, intergroup difference p=0.9.Of factors at inclusion, dyslipidaemia, lower levels of high-density lipoprotein (HDL) and carotid plaque in patients and controls, and higher systolic blood pressure, total cholesterol:HDL and LDL:HDL ratios and triglycerides in patients were associated with cIMT progression. Of factors at follow-up, hypertension and blood lipids in patients and HDL in controls were significantly associated with cIMT progression. History of lupus nephritis and a higher average dose of prednisolone used since diagnosis were associated with cIMT progression in patients. Associations of risk factors with cIMT progression were stronger in presence of plaques. Conclusion: We observed a statistically comparable progression of cIMT in patients with mild SLE and controls over 7 years, which implies that progression of subclinical atherosclerosis in some patients with SLE could follow that of the general population. Traditional cardiovascular (CV) risk factors, history of lupus nephritis and higher use of corticosteroids promote cIMT progression in SLE. Detection of carotid plaque may add to CV risk stratification.