Carotid Artery Disease in Subjects with Type 2 Diabetes: Risk Factors and Biomarkers.
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ABSTRACT:
SUBMITTER: Klimontov VV
PROVIDER: S-EPMC8745306 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Carotid artery disease is considered a major cause of strokes and there is a need for early disease detection and management. Although imaging techniques have been developed for the diagnosis of carotid artery disease and different imaging-based markers have been proposed for the characterization of atherosclerotic plaques, there is still need for a definition of high-risk plaques in asymptomatic patients who may benefit from surgical intervention. Measurement of circulating biomarkers is a promising method to assist in patient-specific disease management, but the lack of robust clinical evidence limits their use as a standard of care. The purpose of this review paper is to present circulating biomarkers related to carotid artery diagnosis and prognosis, which are mainly provided by statistical-based clinical studies. The result of our investigation showed that typical well-established inflammatory biomarkers and biomarkers related to patient lipid profiles are associated with carotid artery disease. In addition to this, more specialized types of biomarkers, such as endothelial and cell adhesion, matrix degrading, and metabolic biomarkers seem to be associated with different carotid artery disease outputs, assisting vascular specialists in selecting patients at high risk for stroke and in need of intervention.
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Project description:Extracranial carotid artery atherosclerotic disease is a major contributor to ischemic stroke. Carotid atherosclerotic disease can present with a spectrum of findings ranging from mild carotid intima-media thickness to high-risk vulnerable carotid plaque features and carotid stenosis. Before leading to clinically overt stroke or transient ischemic attack, there may be other markers of downstream ischemia secondary to carotid atherosclerotic disease. In this review article, we will review some of the imaging findings that may be seen downstream to carotid artery disease on various imaging modalities, including hemodynamic and perfusional abnormalities which may be seen on CT, MR, or using other advanced imaging techniques, white matter hyperintensities on brain imaging, silent or covert brain infarctions, cerebral microbleeds, and regional and generalized cerebral volume loss. Many of these imaging findings are seen routinely on brain magnetic resonance imaging in patients without overt clinical symptoms. Despite frequently being asymptomatic, many of these imaging findings are also strongly associated with increased risk of future stroke, cognitive impairment, and even mortality. We will review the existing evidence underpinning the associations between these frequently encountered imaging findings and carotid artery atherosclerotic disease. Future validation of these imaging findings could lead to them being powerful biomarkers of cerebrovascular health.
| S-EPMC7607077 | biostudies-literature
Project description:Failure of the blood-brain barrier (BBB) is a critical event in the development and progression of diseases such as acute ischemic stroke, chronic ischemia or small vessels disease that affect the central nervous system. It is not known whether BBB breakdown in subjects with chronic carotid artery stenosis can be restrained with postoperative recovery of cerebral perfusion. The aim of the study was to assess the short-term effect of internal carotid artery stenting on basic perfusion parameters and permeability surface area-product (PS) in such a population. Forty subjects (23 males) with stenosis of >70% within a single internal carotid artery and neurological symptoms who underwent a carotid artery stenting procedure were investigated. Differences in the following computed tomography perfusion (CTP) parameters were compared before and after surgery: global cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and PS. PS acquired by CTP is used to measure the permeability of the BBB to contrast material. In all baseline cases, the CBF and CBV values were low, while MTT and TTP were high on both the ipsi- and contralateral sides compared to reference values. PS was approximately twice the normal value. CBF was higher (+6.14%), while MTT was lower (-9.34%) on the contralateral than on the ipsilateral side. All perfusion parameters improved after stenting on both the ipsilateral (CBF +22.66%; CBV +18.98%; MTT -16.09%, TTP -7.62%) and contralateral (CBF +22.27%, CBV +19.72%, MTT -14.65%, TTP -7.46%) sides. PS decreased by almost half: ipsilateral -48.11%, contralateral -45.19%. The decline in BBB permeability was symmetrical on the ipsi- and contralateral sides to the stenosis. Augmented BBB permeability can be controlled by surgical intervention in humans.
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Project description:This study aimed to test the hypothesis that the risk of major adverse cardiovascular events (MACE) is similar for subjects with asymptomatic mild and moderate carotid artery stenosis (CAS). We enrolled a total of 453 subjects with asymptomatic CAS (30-69%) detected on baseline screening Doppler ultrasound (DUS) examination between January 2008 and December 2010. The follow-up DUS findings and MACE occurrence (fatal or nonfatal myocardial infarction or stroke and all-cause mortality) were compared between subjects with mild (30-49%) and moderate (50-69%) CAS during the 8-year follow-up period. There was no significant difference in the occurrence of MACE between subjects with mild (n = 289) and moderate (n = 164) CAS (13.8% vs. 15.9%, respectively; p = 0.56), although there was a nonsignificant trend toward an increased risk of major ipsilateral stroke in subjects with moderate CAS (1.4% vs. 4.3%; p = 0.06). Multivariate regression analysis indicated that worsening CAS was independently associated with MACE occurrence (hazard ratio [HR], 4.40; 95% confidence interval [CI], 2.65-7.27; p < 0.01), whereas an increased serum high-density lipoprotein cholesterol level was correlated with a decreased risk of MACE (HR, 0.42; 95% CI, 0.23-0.75; p < 0.01). The cumulative risk of MACE in subjects with asymptomatic mild CAS is similar to that in subjects with asymptomatic moderate CAS.
| S-EPMC5856768 | biostudies-literature
Project description:Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (P interaction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.
| S-EPMC6925585 | biostudies-literature
Project description:OBJECTIVE:In type 1 diabetes (T1D), the course of microalbuminuria is unpredictable and timing of glomerular filtration rate (GFR) loss is uncertain. Thus, there is a need to identify the risk factors associated with the development of more advanced stages of kidney disease through large, long-term systematic analysis. RESEARCH DESIGN AND METHODS:Multivariable Cox proportional hazards models assessed the association of baseline and time-dependent glycemic and nonglycemic risk factors for incident macroalbuminuria and reduced estimated GFR (eGFR; defined as <60 mL/min/1.73 m2) over a mean of 27 years in the Diabetes Control and Complications Trial (DCCT) cohort. RESULTS:Higher mean HbA1c (hazard ratio [HR] 1.969 per 1% higher level [95% CI 1.671-2.319]) and male sex (HR 2.767 [95% CI 1.951-3.923]) were the most significant factors independently associated with incident macroalbuminuria, whereas higher mean triglycerides, higher pulse, higher systolic blood pressure (BP), longer diabetes duration, higher current HbA1c, and lower mean weight had lower magnitude associations. For incident reduced eGFR, higher mean HbA1c (HR 1.952 per 1% higher level [95% CI 1.714-2.223]) followed by higher mean triglycerides, older age, and higher systolic BP were the most significant factors. CONCLUSIONS:Although several risk factors associated with macroalbuminuria and reduced eGFR were identified, higher mean glycemic exposure was the strongest determinant of kidney disease among the modifiable risk factors. These findings may inform targeted clinical strategies for the frequency of screening, prevention, and treatment of kidney disease in T1D.
| S-EPMC6489116 | biostudies-literature
Project description:Risk factors for cardiovascular disease (CVD) are well-established in type 2 but not type 1 diabetes (T1DM). We assessed risk factors in the long-term (mean 27 years) follow-up of the Diabetes Control and Complications Trial (DCCT) cohort with T1DM. Cox proportional hazards multivariate models assessed the association of traditional and novel risk factors, including HbA1c, with major atherosclerotic cardiovascular events (MACE) (fatal or nonfatal myocardial infarction [MI] or stroke) and any-CVD (MACE plus confirmed angina, silent MI, revascularization, or congestive heart failure). Age and mean HbA1c were strongly associated with any-CVD and with MACE. For each percentage point increase in mean HbA1c, the risk for any-CVD and for MACE increased by 31 and 42%, respectively. CVD and MACE were associated with seven other conventional factors, such as blood pressure, lipids, and lack of ACE inhibitor use, but not with sex. The areas under the receiver operating characteristics curves for the association of age and HbA1c, taken together with any-CVD and for MACE, were 0.70 and 0.77, respectively, and for the final models, including all significant risk factors, were 0.75 and 0.82. Although many conventional CVD risk factors apply in T1DM, hyperglycemia is an important risk factor second only to age.
| S-EPMC4839209 | biostudies-literature
Project description:Carotid intima-media thickness (cIMT) holds prognostic information for future cardiovascular disease and is associated with the extent of coronary atherosclerosis. We investigated the effect of exercise on cIMT progression in patients with both type 2 diabetes and coronary artery disease (CAD).Patients with type 2 diabetes and CAD (n = 137) were randomized to exercise training or standard follow-up. The 12 month exercise program contained 150 min weekly of combined aerobic and resistance training. High-resolution ultrasonography of the distal part of the common carotid artery (CCA) was performed to measure cIMT before and after the intervention. The CCA and the carotid bulb were scanned for the presence of atherosclerotic plaques. Differences in changes between the randomized groups were calculated by one-way ANCOVA.In the total population no difference in changes of cIMT from baseline to 12 months was observed between the exercise group and controls [-0.016 mm (95 % CI -0.037 to 0.006) vs. -0.007 mm (95 % CI -0.029 to 0.015), p = 0.57]. However, there was a significant interaction between the effect of exercise training and the presence of carotid plaques (p = 0.013), and significant reduced cIMT was demonstrated in the exercise group compared with controls in patients without identified carotid plaques (n = 65) [-0.034 mm (95 % CI -0.060 to 0.008) vs. 0.013 mm (95 % CI -0.011 to 0.038), p = 0.010].One year of exercise training in patients with type 2 diabetes and CAD did not significantly change cIMT progression. However, in patients without identified carotid plaques, beneficial effect of exercise training on cIMT progression was demonstrated.
| S-EPMC4724125 | biostudies-literature
Project description:ObjectivesAlthough carotid artery intima media thickness (CIMT) is a widely used determinant of subclinical atherosclerosis, gray-scale median of the intima-media complex (IM-GSM) of the common carotid artery is a relatively novel measure of echogenicity reflecting composition of the arterial wall. It is important to compare cardiovascular disease (CVD) risk factor correlates across CIMT and IM-GSM to determine whether these measures reflect distinct aspects of atherosclerosis.MethodsBaseline information from a completed randomized clinical trial of 643 healthy postmenopausal women without clinically apparent CVD was included in this cross-sectional study. The women were on average ± SD 61 ± 7 years old, and predominantly non-Hispanic White. CIMT and IM-GSM were measured by high-resolution B-mode ultrasonogram in the far wall of the right common carotid artery. CVD risk factors including age, race, body mass index (BMI), smoking, weekly hours of physical activity, systolic (SBP) and diastolic blood pressure (DBP), lipids, glucose, and inflammatory markers were measured at baseline. Linear regression models were used to assess associations of CVD risk factors with CIMT and IM-GSM. Multivariable models included groups of risk factors added one at a time with and withoutbasic demographic factors (age, race, BMI, physical activity) with model R2 values compared between CIMT and IM-GSM.ResultsIn multivariable analysis, age, Black race, BMI, SBP, and DBP were associated with CIMT (all P < .05), whereas age, Hispanic race, BMI, SBP, physical activity, LDL-cholesterol, and leptin were correlates of IM-GSM (all P < .05). Adjusted for age, race, BMI, and physical activity, the R2 value for SBP was greater for CIMT association, whereas R2 values for lipids, glucose, inflammatory markers, and adipokines were greater for IM-GSM associations.ConclusionsCIMT and IM-GSM assess different attributes of subclinical atherosclerosis. Integrating both measures may provide improved assessment of atherosclerosis in asymptomatic individuals.
| S-EPMC9537358 | biostudies-literature
Project description:Dysbiosis of the gut microbiota has been linked to disease pathogenesis in type 1 diabetes (T1D), yet the functional consequences to the host of this dysbiosis is unknown. Here, we have performed a metaproteomic analysis of 103 stool samples from subjects that either had recent-onset T1D, were high-risk autoantibody positive or low-risk autoantibody negative relatives of individuals with beta cell autoimmunity or healthy individuals to identify signatures in host and microbial proteins associated with disease risk. Multivariate modelling analysis demonstrated that both human host proteins and microbial derived proteins could be used to differentiate new-onset and seropositive individuals from low-risk and healthy controls. Significant alterations were identified between subjects with T1D or islet autoimmunity versus autoantibody negative and control subjects in the prevalence of individual host proteins associated with exocrine pancreas function, inflammation and mucosal function. Data integrationIntegrative analysis combining the metaproteomic data with bacterial abundance showed that taxa that were depleted in new-onset T1D patients were positively associated with host proteins involved in maintaining function of the mucous barrier, microvilli adhesion and exocrine pancreas. These data support the notion that T1D patients have increased intestinal inflammation and decreased barrier function. They also confirmed that pancreatic exocrine dysfunction occurs in new-onset T1D patients and show for the first time that this dysfunction is present in high-risk individuals prior to disease onset. Our data has identified a unique T1D-associated signature in stool that may be useful as a means to monitor disease progression or response to therapies aimed at restoring a healthy microbiota.
2018-11-07 | PXD008870 | Pride