High-Sensitivity C-Reactive Protein Predicts Cardiovascular Risk in Diabetic and Nondiabetic Patients: Effects of Insulin-Sensitizing Treatment with Pioglitazone

Abstract

Abbreviations: (BMI) body mass index, (CVD) cardiovascular disease, (HbA1c) hemoglobin A1c, (HOMA) homeostasis model assessment, (hs-CRP) high-sensitivity C-reactive protein, (LDL) low-density lipoprotein, (PPARγ) peroxisome proliferator-activated receptor-γ Keywords: atherosclerosis, diabetes, hs-CRP, inflammation, insulin resistance, pioglitazone AbstractSystemic inflammatory activity has turned out to play a key pathogenic role in vascular atherosclerosis, insulin resistance, and type 2 diabetes mellitus. Inflammatory biomarkers may therefore be a valuable tool for risk evaluation. Among them, the best evidence to date supports the use of high-sensitivity C-reactive protein (hs-CRP) to monitor insulin resistance and cardiovascular risk in diabetic and nondiabetic individuals. Data suggest that hs-CRP may also participate directly in the process of atherogenesis. A growing number of clinical trials tested the hypothesis that antidiabetic drugs specifically targeting insulin resistance could benefit individuals by reducing inflammation, atherogenesis, and thus cardiovascular risk. One such class are the thiazolidinediones (pioglitazone and rosiglitazone). These agents act as selective ligands of the nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPARγ). This article reviewed published data on hs-CRP changes with the thiazolidinedione agent pioglitazone. Here we found pronounced insulin-sensitizing and anti-inflammatory properties in different clinical settings, including diabetic and nondiabetic individuals. Coadministration of pioglitazone to antilipidemic statin therapy resulted in additional effects on low-grade inflammation, and hs-CRP reduction has been demonstrated to occur independently of glucose lowering. The anti-inflammatory effect appeared to be a rapid physiologic reaction on PPARγ activation and could be observed within a short-term interval after starting pioglitazone therapy. In summary, clinical study results underline the benefit of an early insulin resistance treatment to oppose systemic vascular inflammation and cardiometabolic syndrome in patients with elevated levels of high-sensitivity C-reactive protein.

Influence of atherosclerosis‐related risk factors on serum high‐sensitivity C‐reactive protein levels in patients with type 2 diabetes: Comparison of their influence in obese and non‐obese patients

“…It has been thought that serum hs‐CRP level leads to the development of atherosclerosis5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16. Although various new pharmacological approaches have been introduced to reduce hs‐CRP levels17, 18, 19, 20, 21, 22, 23, 24, 25, 26, there are still many cardiovascular diseases all over the world.…”

“…Indeed, it has been reported that hs‐CRP level is associated with carotid atherosclerosis in patients with type 2 diabetes mellitus5, 6, 7, 8, suggesting that hs‐CRP is a useful marker to predict an accelerated atherosclerotic process. It has also been shown that elevated hs‐CRP levels are associated with increased cardiovascular risk9, 10, 11, 12.…”

Effects of an Adaptogen-Based Supplement on Stress Parameters in Healthy Volunteers

“…Furthermore, the survey findings indicated that the adaptogen /vitamin preparation reduced stress perceptions to a greater extent than the corresponding placebo (Table 5). Elevated HS-CRP is strongly associated with an increased incidence of heart attack, stroke, type 2 diabetes and metabolic syndrome [2,12,[16][17][18][19], and the combination product used in this study significantly reduced these levels.…”

Increased Levels of Inflammatory Marker hsCRP, MDA and Lipid Profile in Non-obese Hypertension Subjects

“…An association between sustained high values of CRP following AMI and adverse outcomes was first reported in 1982 [18]. The higher the maximum CRP recorded, the more severe the infarction suffered, the greater the likelihood of ventricular remodeling, the lower the ejection fraction, and the greater the risk of heart failure, heart rupture, and death [19].…”

“…CRP upregulates the expression of adhesion molecules in ECs that can attract monocytes to the site of injury [17]. In case of chronic low-intensity inflammation CRP damages the glycocalyx of vascular endothelium, causing its Dysfunction and making it more susceptible to proatherogenic factors [18].…”