Combined Effects of Hemoglobin A1c and C-Reactive Protein on the Progression of Subclinical Carotid Atherosclerosis The INVADE Study

Department of Neurology, Technical University of Munich, Munich, Germany.
Stroke (Impact Factor: 5.72). 03/2006; 37(2):351-7. DOI: 10.1161/01.STR.0000199034.26345.bc
Source: PubMed


Glycohemoglobin (hemoglobin A1c [HbA1c]) and high-sensitivity C-reactive protein (hsCRP) are risk indicators for atherosclerosis. Limited information exists regarding the combined effects of inflammation and hyperglycemia. We investigated the joint effects of both parameters on early carotid atherosclerosis progression and major vascular events in diabetic and nondiabetic subjects.
We analyzed the data of INVADE (Intervention Project on Cerebrovascular Diseases and Dementia in the Community of Ebersberg, Bavaria), a prospective, population-based study conducted in 3534 subjects (mean age, 69 years). In addition to common risk factors, measurements of carotid intima-media thickness (IMT), hsCRP, and HbA1c were performed at baseline and after 2 years of follow-up.
For the entire population, IMT progression was significantly related to HbA1c (P=0.003) but not to hsCRP (P=0.06) after risk factor adjustment. The interaction hsCRPxHbA1c was highly significant (P=0.001), and the most pronounced IMT progression was seen in subjects with both parameters in the fourth quartiles compared with subjects with both parameters in the first quartiles (0.028 [0.025, 0.031] versus 0.012 mm/year [0.007, 0.019]; P=0.0013). We observed a significant joint effect of HbA1c and hsCRP on IMT progression in the diabetic (n=882) as well as the nondiabetic subgroup (n=2652). Subjects with HbA1c and hsCRP in the upper 2 quartiles had an increased risk for new vascular events (adjusted hazard ratio in diabetics: 4.3 [1.8, 7.3]; P=0.001; nondiabetics: 2.9 [1.6, 4.7]; P=0.001).
The combination of hyperglycemia and inflammation is associated with an advanced early carotid atherosclerosis progression and an increased risk of new vascular events in diabetic as well as nondiabetic subjects.

  • Source
    • "Furthermore, increased levels of HbA1c are reported to be associated with the presence of coronary atherosclerosis and atherosclerosis burden [5]. In addition, few other studies have shown the relationship between HbA1c and atherosclerosis in nondiabetic patients [4,15-20]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The effects of glucose on cardiovascular events or mortality in nondiabetic patients has been recently reported. However, since atherosclerosis can be formed over a long period of time, it is necessary to devote several years to unveil the relationship between the two factors. Here, we attempted to find out the relationship between the mean hemoglobin A1c (HbA1c) level and HbA1c variability for 5 years and coronary artery disease (CAD) by using coronary angiography (CAG) to assess nondiabetic patients. We reviewed patients who performed CAG who were followed up for at least 5 years after the initial diagnosis. The fasting blood test was performed annually for glucose and HbA1c level. CAD was defined as more than 50% of luminal narrowing. The severity of CAD was divided into two groups depending on whether no vessels were involved or one more vessel were involved (CAD(-) or CAD(+), respectively). The patients in CAD(+) group had higher mean HbA1c level for 5 years than CAD(-) group (5.71±0.40 vs. 5.86±0.68; P=0.04). Mean HbA1c was a significant predictor for CAD in multiple regression (odds ratio, 2.224; P=0.028). The percentage of patients with CAD was significantly higher in patients with >6.2% of mean HbA1c levels compared to patients with <6.2% of mean HbA1c levels (P<0.019). When the mean HbA1c levels were above 6.2%, the risk of CAD was higher. Also this study shows that HbA1c level can be one of the predictors for CAD even if the patients do not have diabetes.
    Full-text · Article · Feb 2014 · Diabetes & metabolism journal
  • Source
    • "Won, et al.18 recently reported that MS and its individual components had a significant impact on subclinical atherosclerosis in conditions without diabetes, and a concurrent diagnosis of MS in subjects with established diabetes might be of little value for the risk stratification of CVD. Previous studies also suggested that the progression of atherosclerosis may be independently associated with long-term hyperglycemia in patients with established diabetes.19,20 The present study evaluated the usefulness of MS compared with diabetes as a prognostic concept in patients with CLI treated with PTA, which is an effective therapeutic method for salvaging limbs from both major and minor amputation.21,22 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Metabolic syndrome (MS) is a clinical condition that shares many common characteristics with diabetes. However, unlike diabetes, the usefulness of MS as a prognostic entity in peripheral arterial disease is uncertain. This study evaluated the prognostic usefulness of MS in critical lower limb ischemia (CLI) patients. Materials and Methods We compared the 2-year clinical outcomes in 101 consecutive CLI patients (66±14 years; 78% men) with 118 affected limbs treated with percutaneous transluminal angioplasty (PTA) according to the presence of MS and diabetes. Results The number of MS patients was 53 (52%), of which 45 (85%) had diabetes. During a 2-year follow-up, the incidence of clinical outcomes, including reintervention, major amputation, minor amputation, and survival, was not significantly different between MS and non-MS patients; however, the incidence of minor amputation was significantly higher in diabetic than in non-diabetic patients (42% vs. 17%; p=0.011). Cox regression analysis for the 2-year primary patency demonstrated no association between MS and 2-year primary patency [hazard ratio (HR), 1.02; 95% confidence interval (CI), 0.45-2.30; p=0.961], whereas there was a significant association between diabetes and 2-year primary patency (HR, 2.81; 95% CI, 1.02-7.72; p=0.046). Kaplan-Meier analysis revealed no significant difference in the 2-year primary patency between MS and non-MS patients; however, the 2-year primary patency was lower in diabetic than in non-diabetic patients (p=0.038). Conclusion As a prognostic concept, MS might conceal the adverse impact of diabetes on the prognosis of CLI patients treated with PTA.
    Full-text · Article · Jan 2014 · Yonsei medical journal
  • Source
    • "On the contrary, vascular thickness reflected in carotid IMT and plaque was influenced by MS components, including increased waist circumference and blood pressure, and decreased HDL; however, no MS components significantly affected vascular thickness in diabetics. These results suggest that the progression of atherosclerosis might be directly dependent upon hyperglycemia in patients with established diabetes status [15,16] but might be influenced by multiple CV risk factors, especially the component of increased blood pressure [17], in patients with a status of MS without diabetes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Metabolic syndrome (MS) is associated with increased risks of diabetes and atherosclerotic cardiovascular disease. However, data on the impact of MS and its individual components on subclinical atherosclerosis (SCA) according to diabetes status are scarce. Methods Surrogate markers of SCA, brachial–ankle pulse wave velocity (baPWV), and carotid intima–medial thickness (IMT) and plaque were assessed in 2,560 subjects (60 ± 8 years, 33% men) who participated in baseline health examinations for a community-based cohort study. Results The participants included 2,149 non-diabetics (84%) and 411 diabetics (16%); 667 non-diabetics (31%) and 285 diabetics (69%) had MS, respectively. Diabetics had significantly higher baPWV and carotid IMT, and more plaques than non-diabetics (p < 0.001, respectively). Individuals with MS had significantly higher baPWV and carotid IMT than those without MS only among non-diabetics (p < 0.001, respectively). Among MS components, increased blood pressure was significantly associated with the exacerbation of all SCA markers in non-diabetics. The number of MS components was significantly correlated with both baPWV and carotid IMT in non-diabetics (baPWV: r = 0.302, p < 0.001; carotid IMT: r = 0.217, p < 0.001). Multiple regression showed both MS and diabetes were significantly associated with baPWV (p < 0.001, respectively), carotid IMT (MS: p < 0.001; diabetes: p = 0.005), and the presence of plaque (MS: p = 0.041; diabetes: p = 0.002). Conclusions MS has an incremental impact on SCA in conditions without diabetes. The identification of MS and its individual components is more important for the risk stratification of CVD in non-diabetic individuals.
    Full-text · Article · Mar 2013 · Cardiovascular Diabetology
Show more