The predictive role of early CRP values for one-year mortality in the first 2 d after acute myocardial infarction.

BACKGROUND: An excessive inflammatory reaction after acute myocardial infarction (AMI) is known to be harmful. New anti-inflammatory therapies are required. PURPOSE: This study assessed the predictive role of early CRP in patients with STEMI. METHODS: A total of 1003 patients with STEMI were analysed. A total of 180 patients with proven infection were excluded. CRP after 12, 24 and 48 h after pain onset were evaluated. RESULTS: Of 823 patients, 103 (12.5%) died within one year after AMI. The deceased patients showed higher CRP, even after already 12 h (6 vs. 13 mg/l, p < .001), 24 h (13 vs. 25 mg/l, p < .001) and after 48 h (40 vs. 92 mg/l, p < .001). A CRP of ≥8 mg/l, 12 h after AMI, was found in 45% and was independently associated with long-term mortality (OR: 2.7, p = .03), after 24 h: CRP ≥ 18 mg/l in 44% (OR: 2.5, p = .03), after 48 h: CRP ≥ 53 mg/l in 44% (OR 1.9, p = .03). Early CRP values correlated strongly with the later maximum value of CRP (p < .001). CONCLUSIONS: Already early CRP values are accurate for risk-prediction following AMI. By identifying patients who are beginning to develop an excessive inflammatory response, it may be possible to identify those who benefit from anti-inflammatory therapies.

Sex-difference in expression and function of beta-adrenoceptors in macrovessels: role of the endothelium.

Estrogen modulates adrenergic reactivity of macrovessels, resulting in weaker α-adrenergic vasoconstriction in females than males. However, the mechanisms governing this important sex-specific difference are not well understood. We hypothesized that vessels of females express more dilatory ß-adrenoceptors, which counteract constrictive effects of α-adrenoceptors. This hypothesis was tested using aortas of normotensive (WKY) and hypertensive rats (SHR), along with human mammary artery. Selective blockade of ß1 (CGP20712) or ß3 (SR59230A), but not ß2 (ICI118,551) adrenoceptors, greatly increased α-adrenergic constriction (norepinephrine) of aorta in female SHRs, but not in male SHRs at 12 weeks of age. Consistently, the selective ß1/ß2 (isoproterenol) and ß3-adrenergic (BRL37344) relaxation was stronger in female SHRs than in males. Removal of endothelium and use of L-NMMA abolished sex-difference in α-adrenergic constriction and ß-adrenergic relaxation. Immunostainings revealed endothelial localization of ß1- and ß3-adrenoceptors. mRNA levels of aortic ß1- and ß3-, but not ß2-adrenoceptors were markedly higher in female than in male SHRs. The sex-specific differences in α-adrenergic constriction and ß-adrenoceptor mRNA levels were age-dependent, predominantly present up to 29 weeks and disappeared at 36 weeks of age. The sex-specific difference was not strain-dependent and was similarly present in normotensive WKY rats. Human mammary artery of women showed a weaker α-adrenergic constriction than arteries of men. This sex-specific difference was prominent at 45-65 years and disappeared with aging. Our results convincingly demonstrate that female macrovessels express more dilatory ß1- and ß3-adrenoreceptors than male vessels with a predominant endothelial localization. This sex-specific difference is functionally relevant in young adults and is attenuated with aging.

Frailty is associated with chronic inflammation and pro-inflammatory monocyte subpopulations.

AIM OF THE STUDY: Frail patients with high grade aortic valve stenosis (AS) undergoing Transcatheter Aortic Valve Implantation (TAVI) have an increased mortality. A connection between frailty and inflammation has been suggested. Monocyte subpopulations are associated with both cardiovascular diseases and chronic inflammatory diseases. This study investigates the association of frailty with monocyte subpopulations and systemic inflammatory parameters in elderly patients undergoing TAVI. METHODS: A total of 120 patients with symptomatic AS was examined. Before TAVI implantation, frailty was assessed by a bedside evaluation (eyeball test). In all patients a flow cytometry analysis has been performed. Monocyte subpopulations were defined as follows: classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+CD16++). Expression of CD11b was measured as a marker for monocyte activation. Pro-inflammatory cytokines such as interleukin IL-8, as well as CRP were measured with Cytometric Bead Array or standard laboratory methods. RESULTS: 28 out of 120 patients were frail. These patients showed both, signs of elevated chronic systemic inflammation reflected by elevated CRP (3.7 (1.4-5.4) vs. 5.9 (3.7-29.1), p = 0.001) and an elevated level of intermediate monocytes (37 (24-54) vs. 53 (47-63), p = 0.001). At 6 months after TAVI, 19 of 120 patients died, primarily without relevant dysfunction of the implanted aortic valve. Mortality was significantly higher in the frail as compared with non-frail patients (9 of 28 frail patients vs. 10 of 92 non frail patients, p < 0.001). A binary logistic regression analysis validated frailty and intermediate monocytes as independent predictors for early mortality after TAVI. CONCLUSION: Chronic systemic inflammation and increased levels of intermediate monocytes are associated with frailty in old patients with severe aortic valve stenosis. Both the syndrome of frailty and elevated intermediate monocytes showed an association with early mortality after TAVI.

Endothelial function and gene expression in perivascular adipose tissue from internal mammary arteries of obese patients with coronary artery disease.

BACKGROUND AND AIMS: Obesity is a risk factor for endothelial dysfunction and atherosclerosis. However, perivascular adipose tissue can release adipokines and other unknown adipose-derived relaxing factors. Therefore, we investigated the impact of obesity on vascular function and expression of genes in perivascular adipose tissue from internal mammary arteries of patients with coronary artery disease undergoing coronary artery bypass grafting. METHODS: The vessel function was compared between groups of patients with a body-mass index (BMI) between 25 and 30 kg/m2. The groups did not differ in age, gender (males), and ejection fraction. Vascular segments of internal mammary arteries were examined in a Mulvany myograph. Following preconstriction with noradrenaline, dose-response curves were assessed for relaxation with acetylcholine and sodium nitroprusside. RESULTS: Maximum contraction in response to potassium and noradrenaline was increased in obese patients with a BMI >30 kg/m2. EC50 of endothelium-dependent relaxation was impaired in patients with a BMI above 25, but below 30 kg/m2. Sodium nitroprusside-mediated maximal relaxation was not different between study groups. Integrin alpha X chain (ITGAX/CD11c) and macrophage mannose receptor (MRC1/CD206) expression was reduced in perivascular adipose tissue of patients with a BMI above 30 kg/m2, while adiponectin (ADPQ) expression was increased in the same tissue. CONCLUSION: Our data suggest a partially reduced endothelial function in internal mammary arteries of adipose patients with a BMI between 25 and 30 kg/m2 undergoing coronary artery bypass grafting surgery. Increased adiponectin expression in perivascular tissue might contribute to maintenance of endothelial function in obese patients with a BMI above 30 kg/m2.