Lower High-sensitivity C-reactive Protein Research Articles

Inflammation and Cardiovascular Disease

Inflammation plays an important role in the development and progression of a variety of cardiovascular conditions, most notably coronary atherosclerosis and congestive heart failure.1,2 A number of inflammatory molecules have been implicated in these processes, including interleukin-1 (IL-1). The IL-1 gene family consists of 3 proteins, IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1ra). IL-1α and IL-1β exert their similar effects by binding to the IL-1 type I receptor. The IL-1 type II receptor also binds IL-1α and IL-1β but acts as a decoy receptor and is not involved in signal transduction, thereby counterbalancing the inflammatory effects of IL-1α and IL-1β. IL-1ra is an endogenous inhibitor of IL-1α and IL-1β, which competitively binds to the IL-1 type I receptor without activating it.3 Article p 2662 Both IL-1 and IL-1ra are produced by endothelial cells, smooth muscle cells, and macrophages. IL-1 secretion is induced by microbial products that stimulate toll-like receptors and by certain endogenous triggers, such as uric acid produced during cell death. Both types of agonists stimulate a cytosolic complex of proteins termed the inflammasome, which activates caspase-1 to enable secretion of IL-1β. The potential of this IL-1β pathway for systemic inflammation is demonstrated not only by gout but also by the clinical effects of activating mutations in cryopyrin (also known as NALP3 or CIAS1), one of the inflammasome components, which causes familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease.4 Circulating levels of IL-1 are associated with the presence of traditional cardiac risk factors, such as diabetes mellitus, hypertension, smoking, and dyslipidemia. Elevated levels of IL-1 result in secretion of chemokines and other cytokines (eg, IL-6), increased expression of adhesion molecules, activation of endothelial and smooth muscle cell proliferation, macrophage activation, and increased vascular permeability. This cascade promotes atherosclerosis and plaque destabilization. IL-1 and …

High-sensitivity C-reactive protein predicts target organ damage in Chinese patients with metabolic syndrome

Observational studies established high-sensitivity C-reactive protein as a risk factor for cardiovascular events in the general population. The goal of this study was to determine the relationship between target organ damage and high-sensitivity C-reactive protein in a cohort of Chinese patients with metabolic syndrome. A total of 1082 consecutive patients of Chinese origin were screened for the presence of metabolic syndrome according to the National Cholesterol Education Program's Adult Treatment Panel III. High-sensitivity C-reactive protein and target organ damage, including cardiac hypertrophy, carotid intima-media thickness, and renal impairment, were investigated. The median (25th and 75th percentiles) of high-sensitivity C-reactive protein in 619 patients with metabolic syndrome was 2.42 mg/L (0.75 and 3.66 mg/L) compared with 1.13 mg/L (0.51 and 2.46 mg/L) among 463 control subjects ( P < .01). There was a progressive increase in high-sensitivity C-reactive protein level with the number of components of the metabolic syndrome. Stratification of patients with metabolic syndrome into 3 groups according to their high-sensitivity C-reactive protein concentrations (<1.0, 1.0-3.0, and >3.0 mg/L) showed that the subjects with the elevated high-sensitivity C-reactive protein had a higher percentage of target organ damage than those with lower high-sensitivity C-reactive protein. Stepwise multiple logistic regression confirmed that high-sensitivity C-reactive protein was significantly associated with cardiac hypertrophy, carotid intima-media thickness, and renal impairment. The study shows a strong independent association between inflammation and target organ damage in a large cohort of patients of Chinese origin with metabolic syndrome.

Correlations of high-sensitivity C-reactive protein and atherosclerosis in Japanese type 2 diabetic patients

The elevated level of high-sensitivity C-reactive protein (HSCRP) and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the HSCRP correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 46 Japanese patients with type 2 diabetes and high HSCRP group (0.3-1.0 mg/dl, age: 57+/-5 years, mean+/-s.d.) and a control group of 55 age-matched patients with low HSCRP group (<0.3 mg/dl, 57+/-6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method and was used as an index of atherosclerosis. The body mass index (BMI) values (P<0.05) and waist circumferences (P<0.0005) and the waist-to-hip ratios (P<0.05) were higher in the high HSCRP group than in the low HSCRP group. The BaPWV was higher in the high HSCRP group than in the low HSCRP group (P<0.0001). Fasting plasma glucose (FPG; P<0.005) and insulin concentrations (P<0.0001), and the homeostasis model assessment (HOMA) index (P<0.0001), were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis showed that HSCRP levels were independently predicted by BaPWV and HOMA index. Our results indicate that the elevated level of HSCRP in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and HOMA index are independent predictors of HSCRP.

VO2 peak Relates to Endothelial Function Independently of Other Cardiovascular Disease Risk Factors in Postmenopausal Women

Following the menopause, endothelial function is reported to deteriorate independently of changes in other cardiovascular disease (CVD) risk factors and its decline is an independent predictor for the development of CVD. Whether greater cardio-respiratory fitness (CRF) is related to improved endothelial function in postmenopausal women is unclear. PURPOSE This investigation aimed to examine the interrelationships between CRF (VO2 peak), CVD risk factors and endothelial function in 77 apparently healthy postmenopausal women (age 57.2 ± 3.6yr). METHODS: VO2 peak was assessed via a Bruce treadmill test, and body composition via skinfold analysis and measurement of waist and hip circumferences, BMI and body mass. A fasting venous blood sample was analysed for total cholesterol, high (HDL-C) and low density lipoproteins, triglycerides, glucose, insulin, glycosylated haemoglobin (HbA1c) and high sensitivity C-reactive protein (hsCRP). Flow mediated dilation (FMD) during reactive hyperaemia was recorded as an index of endothelial function. Relationships between variables were assessed using Pearson's correlation. Women were grouped into tertiles of CRF (low: 20.3 ± 1.1; medium: 25.3 ± 2.3; high: 33.2 ± 2.0 ml·kg·min-1), and group differences in CVD risk variables were assessed using ANOVA. The groups did not differ in age or years postmenopause (P > 0.05). RESULTS FMD was significantly correlated with VO2 peak (r = 0.31, P<0.01), and [hsCRP] (r = −0.25, P<0.05). The relationship between FMD and VO2 peak remained following normalization for [hsCRP] (P < 0.05). FMD also significantly differed between CRF groups (low: 3.5 ± 2.5; medium: 4.3 ± 2.7; high: 6.4 ±1.7 %), as did [HDL], [hsCRP] and all body composition variables (P < 0.05). The significant increase in FMD with greater CRF remained when [HDL], [hsCRP] or any body composition variable was included as a covariate (P < 0.05). CONCLUSION In postmenopausal women, endothelial function is significantly and positively related to CRF and this relationship is independent of differences in other key CVD risk factors. This work was Supported by a grant from Heart Research UK (2508/06/08)

Mediterranean Diet and Cardiovascular Disease

In the early 60s, data from the Seven Countries Study demonstrated that diet was a key risk factor for cardiovascular disease (CVD). Several epidemiological studies have since then provided further support to this concept by demonstrating that adherence to a Mediterranean food pattern was associated with a reduction in total and CVD mortality. The mechanisms underlying the cardioprotective effects of the Mediterranean diet (MEDdiet) remain unclear. Our objective was to provide an overview of how a Mediterranean food pattern modulates traditional and non-traditional risk factors for CVD. Data reviewed herein indicated that the MEDdiet may beneficially alter total cholesterol, LDL-C and TG levels, although this has not been a consistent finding. However, the impact of the MEDdiet on non-traditional risk factors such as a lower plasma apolipoprotein B concentrations, a lower high-sensitivity C-reactive protein and interleukin-6 levels, and a better endothelial function appears to be more consistent. In conclusion, adherence to a MEDdiet has been almost unequivocally associated with a decrease in mortality and this may be largely attributable to the more consistent impact of this food pattern on non-traditional risk factors for CVD rather than on traditional risk factors.

High-sensitivity C-reactive protein is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients

We tested the hypothesis that elevated levels of plasma high-sensitivity C-reactive protein (HSCRP) are associated with insulin resistance/hyperinsulinemia and cardiovascular autonomic dysfunction in type 2 diabetic patients without insulin treatment. The study group consisted of 17 type 2 diabetic patients with high HSCRP (0.3-1.0 mg/dL; age, 59 ± 8 years, mean ± SD; high HSCRP group). The control group consisted of 18 age-matched type 2 diabetic patients with low HSCRP (<0.3 mg/dL; 59 ± 7 years; low HSCRP group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentration, and cardiac metaiodobenzylguanidine (MIBG) labeled with iodine 123 scintigraphic findings. Baroreflex sensitivity was lower in the high HSCRP group than in the low HSCRP group ( P < .05). Early and delayed 123I-MIBG myocardial uptake values were lower ( P < .05 and P < .005, respectively) and the percent washout rate of 123I-MIBG was higher ( P < .01) in the high HSCRP group than in the low HSCRP group. Fasting plasma insulin concentration ( P < .01) and the homeostasis model assessment index ( P < .01) were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis revealed that the level of HSCRP was independently predicted by fasting plasma insulin concentration and myocardial uptake of 123I-MIBG at a delayed phase. Our results suggest that high levels of HSCRP are associated with depressed cardiovascular autonomic function and hyperinsulinemia and that fasting plasma insulin concentration and myocardial uptake of 123I-MIBG at a delayed phase are independent predictors of HSCRP level in our Japanese patients with type 2 diabetes mellitus.

4P-1068 Clinical and laboratory characteristics of apparently healthy individuals and those with atherothrombotic risk factors presenting low high sensitive C-reactive protein concentrations

cDNA rat stress microarrays were used to test the general hypothesis that atypical gene expression patterns exist in the brains of Hydrocephalic-Texas (H-Tx) compared to normal Sprague–Dawley (SD) rats on embryonic day 18. Sixty-two percent of the 216 target transcripts were detected in at least 2 of 3 replicates, with maximum mean fold change (MFC) ratios (H-Tx:SD) in Bcl-2-related ovarian killer protein (BOK, 3.07) and peroxisome proliferator-activated receptor-alpha (PPAR-α, 0.04). Five (3.73%) of the 134 detected transcripts were elevated and 20 (17.2%) were suppressed more than twofold in H-Tx. MFC ratios for stress response, cytoskeleton-motility, and intracellular transducer–effector–modulator functional classifications were elevated, while MFC ratios for transcription and apoptosis groups were suppressed in H-Tx. K-means clustering revealed several patterns of gene expression with potential biological relevance in apoptosis, intracellular transducer–effector–modulator, metabolism, cell cycle, and stress response transcripts. Multiplex RT-PCR methodology, used to corroborate the cDNA data, captured four distinct temporal expression patterns on embryonic days 16–20 (E16–E20) for HSP27, DnaJ2, HSP47, HSP60, HSP70, HIP, HSP90A, and HSP90β. The discovery of unique chaperone/heat shock expression profiles in the embryonic brains of H-Tx and SD rats is a powerful step towards the development of novel mechanistic hypotheses in the study of hydrocephalus disorders. This is the first study to associate early stress responses with the differential expression of chaperones/heat shock protein-related genes using the H-Tx model of congenital hydrocephalus.