Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1ß, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1ß innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846 .).

Plasma leptin, but not resistin, TNF-α and adiponectin, is associated with echocardiographic parameters of cardiac remodeling in patients with coronary artery disease.

The aim of this research was to assess the relationship between plasma adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-α) levels and echocardiographic parameters of ventricular remodeling in patients with coronary artery disease, without acute myocardial infarction. The study population consisted of 49 patients with echocardiographic measurements performed. After adjustment for age, gender, body mass index, systolic and diastolic blood pressure, and glycaemia, adiponectin was statistically significant associated with interventricular septum thickness (ß = -0.304), left ventricular posterior wall thickness (ß = -0.402), left ventricular end diastolic diameter (LVEDD; ß = 0.385) and left ventricular relative wall thickness (ß = -0.448, p < .05 for all). The associations were no longer significant when only patients without diabetes were included in the analysis. Leptin was associated with LVEDD (ß = -0.354) and left ventricular relative wall thickness (ß = 0.385, p < .05 for all). No associations between resistin, TNF-α and echocardiographic left ventricular parameters assessed were found in these patients. In conclusion, in patients with coronary artery disease and without acute myocardial infarction leptin may represent a potential mechanism of adverse cardiac remodeling. Resistin and TNF-α might not be involved in ventricular remodeling in these patients.

Hemodynamic monitoring using thoracic bioimpedance - an optimal solution for the treatment of hypertension.

Hypertension is a major issue of public health because of its increasing prevalence and multiple complications caused by failing to achieve an efficient blood pressure control. Considering hypertension as a hemodynamic disorder allows to prescribe a tailored therapy guided by individual hemodynamic parameters, therefore leading to an increased rate of control. We present the case of a 59 years old diabetic, dyslipidemic and obese male who, although treated with 5 classes of antihypertensive drugs had uncontrolled hypertension that caused left ventricular failure. Using the HOTMAN system of hemodynamic monitoring using thoracic electrical bioimpedance allowed a quick identification of the cause and guided the therapy, achieving blood pressure control after 5 days of treatment. Treating hypertension by identifying the underlying hemodynamic imbalance allows prescribing a tailored therapy and shortens the initiation and stabilization phases of treatment.

Serum Soluble ST2 and Diastolic Dysfunction in Hypertensive Patients.

BACKGROUND: Echocardiographic evaluation of left ventricular (LV) structural and functional alterations in hypertension has some limitations, potentially overcome by using biomarkers. ST2, a prognostic biomarker for heart failure and myocardial infarction patients, was less studied in hypertension. AIM: To analyze the relationship between serum ST2 levels and diastolic dysfunction (DD) in hypertension. METHOD: We enrolled 88 hypertensive outpatients (average age 65 years, 69.3% females) in a prospective study, stratified for presence of LV hypertrophy (LVH). For each patient clinical examination, lab workup (routine and serum ST2 levels) and echocardiography were performed. RESULTS: Hypertensive patients with LVH had higher age, pulse pressure, mean arterial pressure, and serum ST2, while having lower serum albumin than those without LVH. Serum ST2 levels correlate with parameters of LV remodeling and DD. We found that 5.3% of ST2 level variability was caused by a 1-unit variation of cardiovascular risk. We identified cut-off values for discriminating hypertension with LVH versus that without LVH and grade 2 DD versus normal diastolic performance. CONCLUSION: ST2 could be used as diagnostic biomarker for cardiac remodeling and altered diastolic performance in hypertension, providing additional data to echocardiography. It could represent a milestone in early detection of cardiac performance alteration.

The Apelin-APJ System in the Evolution of Heart Failure.

Heart failure is a chronic, progressive disease in which the overexpression of biologically active molecules and neurohomonal activation are the key factors of the evolution and natural history. The apelin-APJ system is a newly discovered molecular pathway and the RAAS counterbalance is its principal effect. The apelin is a potent inotrope, vasodilator and diuretic with crucial cardioprotective effects against angiotensin and aldosterone injuries. Intense and prolonged RAAS induces the downregulation of the apelin and its receptor at myocardial level and cancels their protection. Compared to the vasoactive agents used in the treatment of acute heart failure, exogen apelin has unique intropic and vasodilatory effects without deleterious consequences, being a promising therapeutic option.