Anti-ApoA-I IgG antibodies are not associated with carotid artery disease progression and first-time cardiovascular events in middle-aged individuals.

OBJECTIVE: IgG antibodies against apolipoprotein A-I (ApoA-I) have been found to be elevated in subjects from the general population with clinically manifest cardiovascular disease and in myocardial infarction patients with an adverse prognosis. Here, we investigated whether these antibodies are prospectively associated with carotid artery disease progression and with the risk for first-time cardiovascular events in individuals with no previous history of cardiovascular disease. APPROACH AND RESULTS: We selected 383 subjects from the cardiovascular cohort of Malmö Diet and Cancer study who suffered a coronary event during a median follow-up period of 15.4 (10.3-16.4) years and 395 age- and sex-matched controls. None of the study participants had a previous history of coronary artery disease or stroke. Anti-ApoA-I IgG were measured by ELISA in serum samples collected at baseline. Intima-media thickness (IMT) was measured in the common carotid artery and in the carotid bifurcation at baseline and after 15.9 (±1.5) years. We found no associations between anti-ApoA-I IgG and carotid artery IMT at baseline or with IMT progression during follow-up. In Cox proportional hazards analyses adjusted for traditional cardiovascular risk factors, the hazard ratio (HR 95%CI) for the primary outcome, incident coronary events, was 0.97 (0.75-1.25), P = 0.782, in subjects with anti-ApoA-I IgG within the highest tertile compared with the lowest tertile. Similarly, we did not find any associations with the secondary outcome, incident first-time stroke. CONCLUSIONS: Serum autoantibodies against ApoA-I do not correlate with disease progression and adverse events in cardiovascular disease-free individuals from the general population.

Stress-induced release of the S100A8/A9 alarmin is elevated in coronary artery disease patients with impaired cortisol response.

Psychological stress is thought to be an important trigger of cardiovascular events, yet the involved pathways and mediators are largely unknown. Elevated systemic levels of the pro-inflammatory alarmin S100A8/A9 correlate with poor prognosis in coronary artery disease (CAD) patients. Here, we investigated the links between S100A8/A9 release and parameters of anti-inflammatory glucocorticoid secretion in two different cohorts subjected to a psychological stress test. In the first cohort of 60 CAD patients, psychological stress induced a rapid increase of circulating S100A8/A9. This rapid S100A8/A9 response strongly correlated with elevated evening saliva cortisol levels, suggesting an association with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. In the second cohort of 27 CAD patients and 28 controls, elevated S100A8/A9 levels were still detectable 24 h after stress in 40% of patients and 36% of controls, with a tendency for higher levels in patients. The sustained S100A8/A9 response was associated with a poor rapid cortisol release after stress in patients, but not in the control group. Our findings reveal for the first time that acute psychological stress induces elevated levels of S100A8/A9. We also provide hypothesis-generating evidence that dysregulated cortisol secretion in CAD patients might be associated with an exaggerated pro-inflammatory S100A8/A9 response.

Low-dose rapamycin treatment increases the ability of human regulatory T cells to inhibit transplant arteriosclerosis in vivo.

Regulatory T cells (T(reg)) are currently being tested in clinical trials as a potential therapy in cell and solid organ transplantation. The immunosuppressive drug rapamycin has been shown to preferentially promote T(reg) expansion. Here, we hypothesized that adjunctive rapamycin therapy might potentiate the ability of ex vivo expanded human T(reg) to inhibit vascular allograft rejection in a humanized mouse model of arterial transplantation. We studied the influence of combined treatment with low-dose rapamycin and subtherapeutic T(reg) numbers on the development of transplant arteriosclerosis (TA) in human arterial grafts transplanted into immunodeficient BALB/cRag2(-/-) Il2rg(-/-) mice reconstituted with allogeneic human peripheral blood mononuclear cell. In addition, we assessed the effects of the treatment on the proliferation and apoptosis of naïve/effector T cells. The combined therapy efficiently suppressed T-cell proliferation in vivo and in vitro. Neointima formation in the human arterial allografts was potently inhibited compared with each treatment alone. Interestingly, CD4(+) but not CD8(+) T lymphocytes were sensitive to T(reg) and rapamycin-induced apoptosis in vitro. Our data support the concept that rapamycin can be used as an adjunctive therapy to improve efficacy of T(reg)-based immunosuppressive protocols in clinical practice. By inhibiting TA, T(reg) and rapamycin may prevent chronic transplant dysfunction and improve long-term allograft survival.

Plasma procalcitonin and the risk of cardiovascular events and death: a prospective population-based study.

OBJECTIVES: A number of inflammatory biomarkers such as C-reactive protein (CRP) are independent predictors of cardiovascular risk. The inflammatory biomarker procalcitonin (PCT) has previously been shown to be associated with coronary atherosclerosis and the metabolic syndrome. We evaluated the ability of PCT to predict future cardiovascular events in a population of apparently healthy individuals. DESIGN: We measured plasma PCT levels in 3713 subjects with no previous history of cardiovascular disease, randomly selected from the Malmö Diet and Cancer cohort. The correlation between PCT concentration and the incidence of coronary events, stroke and cardiovascular death over a median follow-up period of 13.7 years was studied using a Cox regression analysis corrected for age, sex, CRP level, traditional risk factors and renal function. RESULTS: Age and sex were strong determinants of PCT; the concentration of PCT was significantly higher in men than in women. PCT was associated with several of the established cardiovascular risk factors (CRP, hypertension, diabetes and renal function) as determined by multivariate linear regression. Of note, PCT was inversely correlated with HDL and smoking. We found significant correlations between PCT levels, coronary events and cardiovascular death. However, these relationships lost statistical significance when the analysis was corrected for CRP and the traditional risk factors. CONCLUSIONS: This is the largest population-based prospective study to demonstrate a positive association between plasma PCT levels and cardiovascular risk in subjects with no previous history of acute cardiovascular events. However, the high degree of covariation between PCT and other cardiovascular risk factors limits the value of PCT as an independent cardiovascular risk predictor.