Mean Common Carotid Intima-media Thickness Research Articles

Sonographic evaluation of common carotid artery intima-media thickness in adults with coexisting type two (2) diabetes and hypertension: A case-controlled study

Diabetes mellitus (DM) and hypertension (HTN) are the two leading risk factors for atherosclerosis. Carotid intima-media thickness (CIMT) is considered a reliable surrogate measure for detecting subclinical atherosclerosis including its progression and regression. The study aim at evaluating the intima-media thickness of the common carotid artery in adults with coexisting diabetes mellitus and hypertension (DM+HTN) and compare with healthy controls.. A prospective case control study involving 115 adult subjects with coexisting DM+HTN and 144 healthy adult controls was carried out. Common carotid intima-media thickness (CCIMT) was measured at point approximately 1 cm distal to the right and left carotid bulb using the 7-12 MHz, multi-frequency linear array transducer of high resolution, touch Venue 50 ultrasound machine equipped with electronic callipers. The overall mean CCIMT was 1.13±0.40 mm and 0.82±0.23 mm for subjects with coexisting DM and HTN; and healthy controls, respectively. There was a statistically significant difference in CIMT of subjects with DM+HTN compared to healthy controls (p=0.000 each for both males and females, respectively). There were positive correlations between CCIMT and age in subjects with DM+HTN (r=0.260 and r=0.424 for males and females respectively); with healthy controls (r=0.619 and 0.626 for males and females, respectively). There was a statistically significant difference in CCIMT between subjects with DM+HTN and healthy controls. This implies that the increase in CCIMT is associated with both DM and HTN. In addition, age has a significant positive relationship with CCIMT in both subjects with DM+HTN and healthy controls.

Effect of lifestyle interventions on carotid arterial structure – The DR's EXTRA study

No lifestyle-based interventions with medium-term duration on carotid atherosclerotic have been performed so far. We aimed to investigate whether guideline-based dietary and physical activity interventions slow the progression of atherosclerotic changes in the general elderly population.1410 Finnish men and women from a representative population sample were randomly assigned to one of six groups in the four-year intervention study: 1) reference, 2) aerobic training, 3) resistance training, 4) Nordic Diet, 5) aerobic training + Nordic Diet, 6) resistance training + Nordic Diet. The primary outcome was mean common carotid artery intima-media thickness (cIMT). The lumen diameter of the common carotid artery (cLD) was also analyzed.567 men and 565 women aged 57 to 78 years were included. None of the intervention groups significantly slowed cIMT progression compared to the reference group. A subgroup analysis showed that men in the diet group had significantly smaller cIMT progression than in the reference group (−0.078 mm, 95% CI: −0.146 to −0.009, p = 0.02) and no significant increase in cIMT (p = 0.23). No other group showed a slowed cIMT progression.Among guideline-based lifestyle interventions, only diet leads to a significantly smaller progression of cIMT in older men of a representative population sample. No other lifestyle intervention contributed to a slowing of the progression of structural carotid markers. It must be questioned whether the guideline-based recommendations for a lifestyle change that were in place until recently are adequate to decelerate the atherosclerotic process.

Assessment of Cardiovascular Function in Childhood Leukemia Survivors: The Role of the Right Heart.

Childhood acute lymphoblastic leukemia (ALL) survivors who underwent chemotherapy with anthracyclines have an increased cardiovascular risk. The aim of the study was to evaluate left and right cardiac chamber performances and vascular endothelial function in childhood ALL survivors. Fifty-four ALL survivors and 37 healthy controls were enrolled. All patients underwent auxological evaluation, blood pressure measurements, biochemical parameters of endothelial dysfunction, flow-mediated dilatation (FMD) of the brachial artery, mean common carotid intima-media thickness (c-IMT), antero-posterior diameter of the infra-renal abdominal aorta (APAO), and echocardiographic assessment. The ALL subjects had significantly lower FMD (p = 0.0041), higher left (p = 0.0057) and right (p = 0.0021) echocardiographic/Doppler Tei index (the non-invasive index for combined systolic and diastolic ventricular function) as compared to controls. Tricuspid annular plane excursion (TAPSE) was 16.9 ± 1.2 mm vs. 24.5 ± 3.7 mm, p < 0.0001. Cumulative anthracycline doses were related to TAPSE (p < 0.001). The ALL survivors treated with anthracyclines demonstrated systo/diastolic alterations of the right ventricle and reduced endothelial function compared with healthy controls. The early recognition of subclinical cardiac and vascular impairment during follow up is of utmost importance for the cardiologist to implement strategies preventing overt cardiovascular disease considering the growing number of young adults cured after childhood ALL.

Measures of carotid atherosclerosis and fall-related hospitalization risk: The Perth Longitudinal Study of Ageing Women

Background and aimsWe and others have identified links between cardiovascular conditions and poor musculoskeletal health. However, the relationship between measures of carotid atherosclerosis such as focal carotid plaque and common carotid intima media thickness (CCA-IMT) and falls remains understudied. This study examined the association between measures of carotid atherosclerosis and fall-related hospitalization over 11.5 years in community dwelling older women. Methods and results1116 older women recruited in 1998 to a five-year randomized controlled trial to examine the effect of calcium supplementation in preventing fracture and who had undertaken B-mode ultrasound in 2001 (three years after the baseline clinical visit) were included in this study. The participants were followed for over 11.5 years as Perth Longitudinal Study of Ageing Women (PLSAW). Over the follow up period, 428 (38.4%) women experienced a fall-related hospitalization. Older women with carotid plaque had 44% a higher relative hazard for fall-related hospitalization (HR 1.44; 95%CI, 1.18 to 1.76) compared to those without carotid plaque. The association persisted after adjustment for established falls risk factors such as measures of muscle strength and physical function.Each SD increase in the mean and maximum CCA-IMT was also associated with a higher risk of fall-related hospitalizations (HR 1.10; 95%CI, 1.00 to 1.21 and HR 1.11; 95%CI, 1.01 to 1.22, respectively). ConclusionsMeasures of carotid atherosclerosis are associated with a higher risk of fall-related hospitalization independent of established falls risk factors. These findings suggest the importance of vascular health when considering falls risk.

Effect of Lipoprotein Apheresis on Progression of Carotid Intima-Media Thickness in Patients with Severe Hypercholesterolemia

The extent of intervention effects on carotid intima-media thickness (CIMT) can predict the degree of atherosclerotic cardiovascular risk-reduction. We hypothesized that regular lipoprotein apheresis over the course of 10 years might slow down progression of CIMT in patients with severe hypercholesterolemia. This case series describes 10 Caucasian patients (mean age 60 ± 9 years, 70% female, 80% statin intolerant) with a severe hypercholesterolemia phenotype treated with lipoprotein apheresis between 2005 and 2020 (mean duration, 10 ± 4 years). The median pretreatment low-density lipoprotein cholesterol (LDL-C) level was 214 mg/100 ml (95% confidence interval, 145 to 248), lipoprotein(a) (Lp[a]), 26 mg/100 ml (15 to 109; 40% with Lp(a)>60 mg/100 ml). Three patients were diagnosed with a monogenic cause. The baseline mean CIMT was 850 ± 170 µm, and maximum CIMT was 1,040 ± 220 µm across the age range of 46 to 70 years. Acute effects of lipoprotein apheresis determined as a difference before and immediately after the procedure were estimated as a median of 72 ± 8% and 75 ± 7% reduction in the LDL-C and Lp(a) levels, respectively. Using the imputed trajectories, period-specific on-treatment time-weighted averages for LDL-C and Lp(a) were 141 mg/100 ml (interquartile range, 89 to 152; 38% reduction from the baseline) and 24 mg/100 ml (interquartile range, 12 to 119; 19% reduction from baseline), respectively. The number of patients with CIMT above their "vascular age" decreased from 80% to 30% over the treatment course. In conclusion, an increase in CIMT seen with advanced age and severe hypercholesterolemia was halted with lipoprotein apheresis with an estimated annual rate of change in mean common CIMT of -4 µm/y and maximum CIMT of -3 µm/y.

80. Heme Oxygenase-1 Gene promoter and associations with inflammation and subclinical vascular disease in Ugandan adolescents with and without HIV

Abstract Background Heme oxygenase-1 (HO-1) is a cytoprotective enzyme with potent anti-inflammatory, and anti-oxidant effects. The HO-1 response is modulated by functional polymorphisms (a dinucleotide (GT)n repeat length variation) in the HO-1 gene promoter region which have been associated with cardiovascular disease (CVD) susceptibility in adults. HO-1 polymorphisms and their associations with markers of inflammation and CVD in Ugandan adolescents with (HIV+) and without HIV (HIV-) have not been investigated. Methods We included 177 children (92 HIV+, 85 HIV-) enrolled in an ongoing observational cohort study at the Joint Clinical Research Center, Kampala, Uganda. All HIV+ participants were on ART. HO-1 (GT)n allele genotypes were determined by PCR of the (GT)n repeat region followed by fragment size determination on a capillary sequencer in DNA extracted from blood samples. Allele designations were assigned by number of (GT)n repeats: S &amp;lt; 27, M 27-34, or L &amp;gt; 34 repeats. We measured mean common carotid artery intima-media thickness (IMT) as a marker of CVD, markers of systemic inflammation (hsCRP, IL6, sTNFRI), monocyte activation (sCD14 and sCD163), and T-cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+) , oxidized lipids, markers of gut integrity and fungal translocation (BDG). Results Median age (IQR) was 13 (11, 14), 44% were females, 86% had viral load &amp;lt; 20 copies/mL. 19% had a short allele genotype, 37% had a medium allele genotype and 44% had a long allele genotype (Figure). The shortest and longest allele length correlated with lower IMT in HIV- only (r=-0.36 and -0.30, respectively, p≤ 0.01 for both). Among biomarkers, only the medium allele correlated with oxidized lipids in HIV+ and with hsCRP and BDG in HIV- (p≤ 0.05). After adjusting for age, sex, and BMI, the presence of a long allele was associated with lower IMT. This was no longer significant after adjusting for markers of inflammation or oxidized lipids (Table). Heme Oxygenase-1 genotype allele length frequency in Ugandan cohort of HIV+ and HIV- youth 1: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2) and HIV status (positive vs negative) 2: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2), sCD14 (pg/mL) and HIV status (positive vs negative) 3: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2), high sensitivity C reactive protein (ng/mL) and HIV status (positive vs negative) 4: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2), oxidized lipids and HIV status (positive vs negative) Conclusion These findings underscore the potential of the HO pathways in modulating future risk for CVD in adolescents through inflammation. HIV status in this setting, likely influences the associations with the genotype with the risk of CVD. Further studies to validate our findings in this population are required. Disclosures Grace A. McComsey, MD, Gilead (Consultant, Advisor or Review Panel member)Janssen (Consultant, Advisor or Review Panel member)Merck (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Redhill (Research Grant or Support)Roche (Grant/Research Support)Tetraphase, Astellas (Research Grant or Support)Theratechnologies (Consultant)Vanda (Grant/Research Support)ViiV/GSK (Scientific Research Study Investigator, Advisor or Review Panel member)

Abstract 9055: Vascular Age in Patients With Familial Hypercholesterolemia and/or Elevated Lipoprotein(a) Treated With Lipoprotein Apheresis

Introduction: The 2020 ASE guidelines indicate that an average mean carotid intima-media thickness (CIMT) ≥75th percentile for the patient’s age, sex, race/ethnicity is indicative of increased risk of atherosclerotic cardiovascular disease (ASCVD). With each 10 μm/year reduction of CIMT progression there is a relative risk reduction in the ASCVD event rate by 9% (95% confidence interval, 0.87-0.94). Published nomograms of CIMT percentiles determine “vascular age,” defined as the age at which the composite CIMT value for an individual would represent the median value. Hypothesis: Lipid-modifying treatment with lipoprotein apheresis (LA) over the course of 10 years will affect vascular age in patients with baseline elevated CIMT due to severe hypercholesterolemia. Methods: Ten individuals (mean age 60±9 years, 70% female) with familial hypercholesterolemia and/or elevated lipoprotein(a) [Lp(a)] were treated every two weeks with LA (Liposorber, Kaneka, Japan) between 2005 and 2020 (median duration, 12 years). Results: Acute effects of LA included reduction in LDL-C and Lp(a) levels by a median of 72±8% and 75±7%, respectively. The proportion of patients with average mean CIMT ≥75th percentile was 8/10 at the time of apheresis initiation. LA resulted in mean CIMT reduction of –40μm (IQR, –50 to 20). This translated into 70% (7/10) of cases demonstrating composite mean CIMT below their expected vascular age. The follow-up mean CIMT strongly correlated only with the baseline Lp(a) levels. The number of patients with CIMT above their “vascular age” decreased from 80% to 30% over treatment course. The rate of ASCVD was 37.5 per 1000 person-years while on LA. Conclusions: While annual CIMT progression rates average 15 μm/y, an increase in CIMT seen with advanced age and severe hypercholesterolemia was halted with LA with an estimated annual rate of change in mean common CIMT of –4 μm/y and maximum CIMT of –3μm /y. This analysis demonstrates positive impact of LA on vascular age.

An Analytical Cross-Sectional Study to Assess the Effects of Smoking on Common Carotid Intima-Media Thickness and Resistivity Index Among Current Smokers

Objective: The aim was to assess the structural and hemodynamic effects of smoking on the common carotid arteries (CCAs) in current smokers from Himachal Pradesh. In addition, it was important to determine any association between smoking duration, frequency, pack-years, and the occurrence of common carotid atherosclerosis. Materials and Methods: The study evaluated 50 current smokers for common carotid intima-media thickness (CIMT), plaque presence, and resistive index (RI) with sonography. The findings were compared with 50 healthy control patients, who had never smoked. Results: A positive association was observed between smoking and an increase in CIMT ( P = .001) and occurrence of plaques ( P = .007), with substantially higher mean CIMT values in smokers above 45 years ( P &lt; .05) in both genders ( P &lt; .05). No difference in overall RI was seen in both groups taken as a whole, while higher RI values ( P &lt; .05) were noticed in smokers exclusively above 60 years. A positive association was noted between smoking frequency, pack-years, and an increase in CIMT, RI, and occurrence of plaques. For every unit increase in the number of pack-years and smoking duration, there was a 0.01 unit increase in CIMT among the current smokers. Conclusion: This research provides evidence that smoking has a structural impact on CIMT while its hemodynamic effect is still unclear.

A Comparative Study for an Assessment of Arterial Stiffness with Cardio-Ankle Vascular Index and Clinical Determinants between those Individuals with and without Diabetes

Background: Arterial stiffness and dysfunction are clinical determinants in predicting long-term cardiovascular risk in type 2 diabetes (T2DM). Cardio-ankle vascular index (CAVI) is a novel tool in detecting atherosclerosis by measuring arterial stiffness along the aorta to tibial arteries. Objective: To compare clinical parameters between diabetes and non-diabetes groups. The present study explored clinical factors associated with CAVI of 8.0 or more in diabetes patients. Moreover, the study determined the correlation between CAVI and clinical predictors for long-term cardiovascular risk. Materials and Methods: The present study was a retrospective, cross-sectional study. The controls or non-diabetes were matched with the cases or diabetes in ratio 2:1 and aged matched in two groups, 40 years and older and less than 40 years old. Results: Two hundred fifty-two subjects were enrolled, 84 were diabetes and 168 were non-diabetes. The present study found those subjects with high body mass index (BMI) of 25.0 kg/m² or more and CAVI of 8.0 or more were the factors associated with greater risk of having diabetes than non-diabetes. Subjects with T2DM aged 40 years or older had 11.95 times greater risk of having CAVI of 8.0 or more than those younger than 40 years in T2DM (p=0.002). Known essential hypertension was another independent factor associated with 4.28 times greater risk of having CAVI of 8.0 or more than those without hypertension in T2DM (p=0.010). The present study found significant positive correlation between CAVI and the previously reported clinical markers, RAMA-EGAT score and the mean common carotid artery intima-media thickness, that predict long-term cardiovascular events in T2DM (Pearson’s correlation coefficient; r=0.6738 and 0.4207, respectively, p&lt;0.05). Conclusion: Those subjects with CAVI of 8.0 or more and BMI of 25 kg/m² or more had significantly greater association with diabetes than nondiabetes. Age of 40 years or older and history of hypertension were independent risk of high CAVI of 8.0 or more in T2DM. CAVI also correlated with the previously reported clinical marker to predict long-term cardiovascular risk such as RAMA-EGAT score, the mean common carotid artery intima-media thickness in T2DM. Keywords: Type 2 diabetes; Cardio-ankle vascular index (CAVI); Arterial stiffness

Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Role of Fibroblast Growth Factor 23- Phosphate Axis.

PurposeDespite management advances, accelerated atherosclerotic cardiovascular disease (ACVD) remains a major cause of morbimortality in systemic lupus erythematosus (SLE) patients; that is not fully explained by traditional risk factors. Fibroblast growth factor-23 (FGF23) is a bone-derived phosphaturic hormone with multiple klotho-dependent and independent effects, including promotion of atherosclerosis and vascular calcification, particularly in the context of chronic kidney disease. Increased circulating FGF23 was reported in SLE patients, particularly with lupus nephritis (LN); but its atherogenic role in these disorders was not explored.Subjects and MethodsThree study groups of predominantly middle-aged females were categorized by the 2012 SLE International Collaborating Clinics (SLICC) criteria as SLE (without LN), LN, or controls matching for traditional CVD risk profile. Measures of SLE activity, damage, steroid therapy, and glomerular filtration rate were calculated. Fasting blood samples were checked for serum lipid profile, anti-DNA, urea, creatinine, uric acid, proteins, albumin, calcium, phosphorus, C3, C4, CRP, vitamin-D3, intact parathyroid hormone and FGF23 (iFGF23). By carotid ultrasonography, mean common carotid artery intima-media thickness (CC-IMT), plaque score (PS) and internal carotid resistive index (ICRI) were recorded.ResultsCC-IMT, ICRI and serum iFGF23 differed along the study groups (LN>SLE>controls). In both SLE and LN patients, serum iFGF23 had a significant positive correlation with serum phosphorus, CC-IMT and PS. On multivariate analysis, the strongest predictor of increased CC-IMT was cumulative steroid dose in SLE and serum iFGF23 in LN patients. Most significant independent predictors of increased serum iFGF23 were hyperphosphatemia in SLE and proteinuria in LN patients.ConclusionFGF23-phosphate axis has a key role in accelerated ACVD in SLE patients. Serum phosphorus and iFGF23 should be included in ACVD risk profile assessment of these patients. Prospective studies shall define the role of dietary and/or pharmacologic control of hyperphosphatemia and proteinuria in reducing circulating iFGF23 and ACVD in them.

ASSOCIATION OF PARITY AND GRAVIDITY WITH CAROTID INTIMA-MEDIA THICKNESS: THE OHASAMA STUDY

Abstract Objective: We aimed to investigate if any of parity, gravidity and menstrual factors are associated with carotid atherosclerosis diagnosed by ultrasound imaging. Design and method: We identified 543 women aged 60 years or older from the general population of Ohasama, a rural Japanese community, who answered a questionnaire on parity and gravidity and age at menarche, were free of previous cardiocerebrovascular disease. The carotid atherosclerosis was assessed based on the presence of focal carotid plaque and mean common carotid intima-media thickness (IMT) by using ultrasound imaging. Information on possible confounding factors including self-measured blood pressure at home (home BP) was simultaneously obtained. Results: Plaque lesion was observed in 138 (25%) and the median of IMT was 0.68 mm with interquartile range of 0.63–0.75. Means of home systolic and diastolic BP levels were 129.5 ± 14.2 mmHg and 74.0 ± 8.4 mmHg, respectively. Multivariate logistic regression models showed that compared with women who had two children, women who had three children (OR 1.82, 95%CI, 1.12–2.96) and women who had four or more children (OR 2.60, 95%CI, 1.47–4.58) were more likely to have an increased risk with the presence of focal carotid plaque adjusting for age (p &lt; 0.001), body mass index (p = 0.012), hypertensive drug use (p = 0.319), home systolic BP levels (p = 0.364), impaired glucose tolerance (p = 0.230) and hyperlipidemia (p = 0.808), and current smoker (p = 0.955) and drinker (p = 0.294). Adjusting for these covariates, the highest quartile of gravidity (4- vs. 2) was associated with an increased risk of the plaques lesion (OR 2.03; 95%CI: 1.14–3.62) and youngest age quartile of age at menarche (13- y/o vs. 14 years) was associated with a decreased risk of the presence of plaque (OR, 0.51, 95%CI: 0.28–0.92). Multivariate general linear regression model showed that the wall thickness of carotid artery appeared slightly thicker among women who had highest parity quartile (b = 0.036, p = 0.009) adjusting for same covariates. The wall thickness of carotid artery was not associated with both gravidity (p = 0.089) and age at menarche (p = 0.113). Conclusions: Higher parity and gravidity, and younger age at menarche were associated with carotid atherosclerosis, independent of major confounding factors including age and home BP levels.

Association of Carotid Plaques and Common Carotid Intima-media Thickness with Modifiable Cardiovascular Risk Factors

ObjectiveTo assess the association of carotid plaques and common carotid artery intima-media thickness with traditional modifiable cardiovascular risk factors. MethodsWe examined 4,266 participants aged 35–74years in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline. The presence of plaques at all carotid arteries sites was evaluated. The mean far wall common carotid artery intima-media thickness was measured. To evaluate the association of cardiovascular risk factors with plaques and plaque burden, we applied logistic regression models presented as crude, adjusted by sociodemographic variables, along with multivariate further adjustment for hypertension, diabetes, hypercholesterolemia, and smoking. For the association of cardiovascular risk factors and common carotid artery intima-media thickness, linear regression models were used with the same adjustments. ResultsMedian age was 51 years (interquartile range: 45–58 years; 54.5% of females). Plaque prevalence in at least one segment of the carotid arteries was 35.9%. Mean common carotid artery intima-media thickness of the far walls was 0.609 ± 0.133 mm. In the multivariate model for plaque presence, the odds ratios were:1.39 (1.19–1.63) for hypertension;1.58 (1.36–1.82) for hypercholesterolemia; 2.00 (1.65–2.43),1.19 (1.02–1.40) for current and past smoking, and 1.13 (0.95–1.35) for diabetes. In the multivariate linear regression models, common carotid artery intima-media thickness beta-coefficients were: 0.035 mm (0.027–0.043) for hypertension; 0.020 mm (0.013–0.027) for hypercholesterolemia; 0.020 mm (0.010–0.029), 0.012 mm (0.004–0.020) for current and past smoking, and 0.024 mm (0.015–0.033) for diabetes. ConclusionCardiovascular risk factors were independently associated with increasing common carotid artery intima-media thickness, plaque prevalence, and plaque scores. Diabetes did not show an independent association with plaques in the multivariate model.

Carotid Intima-media Thickness in the Algerian Population: Reference ranges and association with cardiovascular risk factors

Carotid intima-media thickness as measured with ultrasonography is an inexpensive and noninvasive predictor of cardiovascular events. The objectives of this study were to determine the population reference ranges of carotid intima-media thickness for individuals aged 35-84 years in Algerian cohort and to analyze the association of carotid intima-media thickness with cardiovascular risk factors (age, smoking, diabetes, pulse pressure, lipid profile, and body mass index). Population-based cross-sectional study conducted in military hospitals of Constantine and algiers (Algeria). We described the mean and maximal values of carotid intima-media thickness of the carotid artery and of its 3 segments (common carotid, carotid bulb and internal carotid). We assessed cardiovascular risk factors and analyzed their association with carotid intima-media thickness using adjusted linear regression models. A total of 1547 individuals (54% women) were included, with mean age 58 years. Men showed significantly higher mean common carotid intima-media thickness than did women (0.71 vs. 0.67 mm). The strongest predictors of this measure were age (coefficients for 10-year increase: 0.65 and 0.58 for women and men, respectively), smoking in men (coefficient: 0.26), high-density lipoprotein cholesterol in women (coefficient for 10 mg/dL, increase: - 0.08) and pulse pressure in both sexes (coefficients for 10 mmHg increase: 0.08 and 0.23 for women and men, respectively). The results were similar for the mean carotid intima-media thickness of all the segments. This population-based study presents the reference ranges for carotid intima-media thickness in the Algerian population. The main determinants of carotid intima-media thickness were age and pulse pressure in both sexes.

Tofogliflozin does not delay progression of carotid atherosclerosis in patients with type 2 diabetes: a prospective, randomized, open-label, parallel-group comparative study

BackgroundThis study aimed to investigate the preventive effects of tofogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD) by monitoring carotid intima-media thickness (IMT).MethodsThis prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study included 340 subjects with T2DM and no history of apparent CVD recruited at 24 clinical units. Subjects were randomly allocated to either the tofogliflozin treatment group (n = 169) or conventional treatment group using drugs other than SGLT2 inhibitors (n = 171). Primary outcomes were changes in mean and maximum common carotid IMT measured by echography during a 104-week treatment period.ResultsIn a mixed-effects model for repeated measures, the mean IMT of the common carotid artery (mean-IMT-CCA), along with the right and left maximum IMT of the CCA (max-IMT-CCA), significantly declined in both the tofogliflozin (− 0.132 mm, SE 0.007; − 0.163 mm, SE 0.013; − 0.170 mm, SE 0.020, respectively) and the control group (− 0.140 mm, SE 0.006; − 0.190 mm, SE 0.012; − 0.190 mm, SE 0.020, respectively). Furthermore, the tofogliflozin and the conventional treatment group did not significantly differ in the progression of the mean-IMT-CCA (mean change (95% CI) 0.008 (− 0.009, 0.025) mm, P = 0.34), along with the right (mean change (95% CI) 0.027 (− 0.005, 0.059) mm, P = 0.10) and the left max-IMT-CCA (mean change (95% CI) 0.020 (− 0.030, 0.070), P = 0.43). Similar findings were obtained even after adjusting for traditional CV risk factors and/or administration of drugs at baseline. Relative to the control treatment effects, tofogliflozin significantly reduced the HbA1c, blood glucose level, body weight/body mass index, abdominal circumference, and systolic blood pressure, and significantly increased the HDL-C. The total and serious adverse events incidences did not significantly vary between the treatment groups.Conclusions/interpretationNo IMT changes were observed between the tofogliflozin and the conventional treatment groups. However, tofogliflozin is a safe and effective treatment option for managing primary CVD risk factors in this population.Clinical Trial Registration UMIN000017607 (https://www.umin.ac.jp/icdr/index.html).

Sitagliptin on Carotid Intima-Media Thickness in Type 2 Diabetes Mellitus Patients and Anemia: A Subgroup Analysis of the PROLOGUE Study.

Introduction Randomized clinical trials have not shown an additional clinical benefit of sitagliptin treatment over conventional treatment alone. However, studies of sitagliptin treatment have not examined the relationship between anemia and treatment group outcomes. Methods The PROLOGUE study is a prospective clinical trial of 442 participants with type 2 diabetes mellitus (T2DM) randomized to sitagliptin treatment or conventional treatment which showed no treatment differences [Estimated mean (± standard error) common carotid intima-media thickness (CIMT) was 0.827 ± 0.007 mm and 0.837 ± 0.007 mm, respectively, with a mean difference of -0.009 mm (97.2% CI −0.028 to 0.011, p = 0.309) at 24 mo of follow-up]. This is a post hoc subanalysis using data obtained from the PROLOGUE study; the study population was divided into anemic groups (n = 94) and nonanemic group (n = 343) based on hemoglobin level. And we analyzed for the changes in each CIMT parameter from baseline to 24 months in subgroups. Results The treatment group difference in baseline-adjusted mean common carotid artery- (CCA-) IMT at 24 months was −0.003 mm (95% CI −0.022 to 0.015, p = 0.718) in the nonanemic subgroup and −0.007 mm (95% CI −0.043 to 0.030, p = 0.724) in the anemic subgroup. Although there were no significant differences in the other CIMT parameters between the treatment groups in the anemic subgroup, the changes in mean and max ICA-IMT at 24 months in the nonanemic subgroup were significantly lower in the sitagliptin group than the conventional group [−0.104 mm (95% CI −0.182 to −0.026), p = 0.009 and −0.142 mm (−0.252 to −0.033), p = 0.011, respectively]. Conclusion These data suggest that nonanemia may indicate a potentially large subgroup of those with T2DM patients that sitagliptin therapy has a better antiatherosclerotic effect than conventional therapy. Further research is needed to confirm these preliminary observations.

Effect of Tofogliflozin on Carotid Intima-Media Thickness in Patients with Type 2 Diabetes: Results from the Prospective, Randomized, Open-Label, Parallel-Group Comparative UTOPIA Trial

Effect of Tofogliflozin on Carotid Intima-Media Thickness in Patients with Type 2 Diabetes: Results from the Prospective, Randomized, Open-Label, Parallel-Group Comparative UTOPIA Trial

The Association of Physical Activity With Carotid Intima Media Thickening in a Healthy Older Population: Cooper Center Longitudinal Study.

The purpose of this study was to examine the association between self-reported physical activity (PA) and mean common carotid artery intima-media thickness (CCA IMT) among older adults. The data are from 1,811 Cooper Center Longitudinal Study participants, who were aged ≥60years, with no history of cardiovascular disease. A medical history questionnaire was used to assess PA. Carotid ultrasound was performed to measure CCA IMT and the presence of plaque and stenosis. Logistic regression models were constructed to estimate the association between PA and CCA IMT after adjustment for covariates. The participants were aged 69.2 ± 5.9years, and the majority were male (73.3%) and White (96.7%). The odds ratio of abnormal thickening of CCA IMT was 0.72 (95% confidence interval [0.54, 0.96]) in physically active participants (≥500 metabolic equivalent·min/week) after adjustment for covariates. In the current study, meeting PA guidelines in older adulthood was associated with lower odds of abnormal thickening of CCA IMT.

Association of platelet-derived microvesicles and their phenotypes with carotid atherosclerosis and recurrent vascular events in patients after ischemic stroke

IntroductionPlatelet-derived microvesicles (pMVs) exhibit procoagulant and proinflammatory properties and play a role in the development and progression of atherosclerosis. The study examined the association between the total number of pMVs and their phenotypes with carotid atherosclerosis and recurrent vascular events (VEs) in patients in the convalescent phase of ischemic stroke (IS). Materials and methodsThe study group consisted of 72 patients with IS secondary to large artery atherosclerosis (LAA) (n = 40) and small arteries occlusion (SAO) (n = 32) and 69 matched cardiovascular disease risk-factor (RF) controls. Total pMV number, defined as CD61+ microvesicles (MVs), and their phenotypes, defined as the surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, PAC-1) markers, were characterized and quantified using flow cytometry. The mean common carotid intima-media thickness (CCA mean IMT), maximal common carotid IMT (CCA max IMT) and maximal bifurcation IMT (BIF max IMT) were measured bilaterally using B-mode, color Doppler ultrasonography. All study subjects were observed for one-year to establish the occurrence of VEs. ResultsNo differences in pMV parameters between LAA and SAO stroke subjects and between stroke subgroups and controls were found. Stroke patients with carotid atherosclerosis exhibited higher concentration of CD62P+/CD61+ and PAC-1+/CD61+ MVs compared to patients without the atherosclerosis. Positive associations between total number of pMVs, AnV+ MVs and AnV+/CD61+ MVs and atherosclerotic thickening of carotid intima-media in stroke patients were found. Elevated concentration of AnV+/CD61+, PAC-1+/CD61+, CD61P+/CD61+ and CD31+/CD61+ MVs, were revealed in stroke patients who suffered from recurrent VE in one-year follow-up period. Negative correlation of pMVs and CD62P+/CD61+ MVs concentration as well as percentage of total CD61+ in AnV+ population of MVs and time elapsed from IS in convalescent stroke subjects was revealed. ConclusionOur results confirm positive correlations between total pMV number, the number of PAC-1+/CD61+ and CD62+/CD61+ MVs and carotid atherosclerosis in stroke subjects. Some pMV parameters may exhibit a predictive value for the next VE in groups with a history of stroke. pMVs and some of their phenotypes decline over time elapsed from stroke in convalescent stroke subjects.

Assessment of carotid intima-media thickness in patients of controlled and uncontrolled type 2 diabetes mellitus

Background: Diabetes mellitus refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. The present study was conducted to determine carotid intima-media thickness in patients of controlled and uncontrolled type 2 diabetes mellitus. Materials & Methods: The present study was conducted on 150 type 2 diabetes mellitus patients (75 in controlled diabetes and 75 in uncontrolled diabetes group) of both genders. All patients underwent carotid doppler of common carotid artery determined by higher resolution B mode ultrasonography using Philips Affinity 70 machine. The total of 3 values was averaged to give mean common carotid intima-media thickness value for each patient. Results: Group I had 40 males and 35 females whereas group II had 45 males and 30 females. The mean diameter of right CCA in group I was 6.4 mm and in group II was 7.3 mm, in left CCA was 6.5 mm and in group II was 6.8 mm, right ICA was 4.5 mm in group I and 4.7 mm in group II and left ICA was 4.6 mm in group I and 4.5 mm in group II. The mean IMT of right CCA in group I was 0.72 mm and in group II was 0.84 mm, in left CCA was 0.74 mm and in group II was 0.87 mm, right ICA was 0.43 mm in group I and 0.48 mm in group II and left ICA was 0.45 mm in group I and 0.54 mm in group II. Conclusion: Authors found increase diameter and thickness of intima media in uncontrolled diabetics as compared to controlled diabetics.

Covariables and types of abnormal left ventricular geometry in nonelderly ischemic stroke survivors: the Norwegian Stroke in the Young Study.

Abnormal left ventricular (LV) geometry types, like LV hypertrophy (LVH) and concentric remodelling, are independently associated with impaired prognosis in hypertension. Little is known about the prevalence and covariables of abnormal LV geometry types in younger ischemic stroke patients. We used clinical and echocardiographic data from 280 patients aged 15-60 years included in the Norwegian Stroke in the Young Study. LVH was defined as LV mass index greater than 46.7 g/m in women and greater than 49.2 g/m in men. Concentric remodelling was considered present if posterior wall thickness/LV internal diameter ratio at least 0.43 in the absence of LVH. Arterial damage was assessed by mean common carotid intima-media thickness (IMT) and carotid-femoral pulse wave velocity (PWV). Abnormal LV geometry was found in 37% of patients. Concentric remodelling was the most prevalent abnormal LV geometry type, found in 21%, whereas LVH was found in 16%. In multivariable logistic regression analyses, LVH was associated with increased PWV, higher BMI and creatinine, and presence of diabetes and hypertension (all P < 0.05), whereas concentric remodelling was associated with higher mean carotid IMT independent of age (both P < 0.05). In ischemic stroke survivors less than 60 years of age, abnormal LV geometry was common, found in 37%. Presence of abnormal LV geometry may contribute to the known higher risk of recurrent cardiovascular events in ischemic stroke survivors.