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-1β, 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-1β 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.

THE EFFECTS OF HIGH-INTENSITY FUNCTIONAL TRAINING ON PERCEPTIONS OF EXERCISE IN MIDDLE-AGED FEMALES

Halle N. Brin1, Camilla L. Roy1, Baylie G. Sigmund1, Nathan D. Dicks2, Kathryn J. DeShaw3, Michael J. Carper1, Laura M. Covert-Miller1, Tanis J. Walch4, Allison M. Barry1. 1Pittsburg State University, Pittsburg, KS; 2Concordia College, Moorhead, MN; 3Loras College, Dubuque, IA; 4University of North Dakota, Grand Forks, ND The high prevalence of obesity and physical inactivity within the U.S. has become a public health crisis. PURPOSE: To examine the effects of High-Intensity Functional Training (HIFT) on the perceptions and beliefs towards exercise in an inactive sample of females. METHODS: Inactive, middle-aged females (n = 8) were recruited to participate in an 8-week supervised and verified intervention (2-weeks High-Intensity Interval Training (On-Ramp), followed by 6-weeks of HIFT) three days per week. Pre- and post-assessments included: body composition (percent body fat (%BF)), strength (1RM bench press (BP), 5RM deadlift (DL)), a stage-graded exercise treadmill test (O2max), and a Health Belief Model Scale for Exercise (HMBS-E). The HBMS-E was distributed weekly to assess changes in perceptions and beliefs towards exercise, consisting of 18 questions formatted into 5-point Likert scales. The HBMS-E questions were grouped into the five sub-categories: perceived objective barriers, perceived subjective barriers, self-efficacy, perceived severity, and cues to action. Comparisons between pre- and post-assessment of the physiological components as well as the HBMS-E categories were assessed using dependent t-tests. SPSS (v. 26) was used for statistical analysis. RESULTS: The participant demographics (age: 39.2 ± 7.7 yrs), performance, and HBMS-E data are reported as pre- to post-intervention, respectively. There was no significant difference in %BF (35.2 ± 6.6% to 34.3 ± 6.0%, p \u3e .05). There was a significant increase in 1RM BP (25.2 ± 10.1 kg to 35.7 ± 11.1 kg; p \u3c .001, d = 2.51; 5RM DL (36.2 ± 12.3 kg to 49.1 ± 9.8 kg; p = .001, d = 1.83); and O2max (23.4 ± 4.0 ml∙kg∙min-1 to 26.4 ± 4.1 ml∙kg∙min-1 ; p = .001, d = 1.81). There was a significant reduction in the HBMS-E sub-categories of objective barriers (3.5 ± 0.7 to 1.9 ± 0.6; p = .003; d = 1.58) and subjective barriers (2.7 ± 0.8 to 1.6 ± 0.5; p = .017, d = 1.09) and significant increase in self-efficacy (3.5 ± 1.4 to 4.6 ± 0.56; p = .016; d = 1.13). CONCLUSION: There is evidence to suggest HIFT has a positive influence on middle-aged females’ perceptions and beliefs of self-efficacy and barriers towards exercise. Additionally, the HIFT intervention had a significant impact on the physiological adaptions of strength in this population