CURBSIDE- September 2010

STUDY ONE:
Title: Waist Circumference and All-Cause Mortality in a Large US Cohort
Date Posted: August 9, 2010
Authors: Jacobs EJ, Newton CC, Wang Y, et al.
Citation: Arch Intern Med 2010;170:1293-1301.

Study Question:
Is waist circumference associated with risk of death within body mass index (BMI) categories?

Methods:
Data from the Cancer Prevention Study II (CPS-II) Nutrition Cohort (established in 1992) were used for the current study. The CPS-II Nutrition Cohort is a subset of the CPS-II cohort established by the American Cancer Society in 1982. Subjects enrolled between 1992 and 1993 and were mailed questionnaires in 1997, in which they were asked to measure their waist circumference. Validity of self-report was not completed. Body mass index (BMI) was calculated from reported weight on the 1997 survey, and height was reported in the 1982 survey. Subjects who had lost ≥10 lbs or gained more than 25 lbs between 1992 and 1997 were excluded. Subjects with missing data on waist circumference or BMI were also excluded. Mortality was assessed through the National Death Index through December 31, 2006.

Results:
A total of 48,500 men and 56,343 women, 50 years or older, were included in this analysis. Median age at baseline was 69 years for men and 67 years for women. The cohort was predominately white. Subjects in the highest category of waist circumference were more likely to be less educated, have a high BMI, be sedentary, and were former smokers compared to subjects with lower waist circumference. This group was also more likely to have a history of cardiovascular disease, cancer, or respiratory disease. Between 1997 and 2006, 9,315 men and 5,332 women had died. After adjustment for BMI and other risk factors, increased waist circumference (≥120 cm compared to <90 cm) was associated with a twofold higher risk of mortality among men (relative risk [RR], 2.20; 95% confidence interval [CI], 1.71-2.39). For women, a waist circumference ≥110 cm compared to <75 cm was also associated with increased risk of death (RR, 2.36; 95% CI, 1.98-2.82). Waist circumference was positively associated with mortality in all categories of BMI. In men, a 10 cm increase in waist circumference was associated with RRs of 1.16 (95% CI, 1.09-1.23) for normal (18.5 to <25) BMI, 1.18 (95% CI, 1.12-1.24) for overweight (25 to <30) BMI, and 1.21 (95% CI, 1.13-1.30) for obese (≥30) BMI. In women, corresponding RRs were 1.25 (95% CI, 1.18-1.32), 1.15 (95% CI, 1.08-1.22), and 1.13 (95% CI, 1.06-1.20).

Conclusions:
The investigators concluded that waist circumference is important as a risk factor for mortality among older adults, regardless of BMI.

Perspective:
These data highlight the clinical significance of waist circumference. Clinicians may want to consider making waist circumference part of the vital signs for each patient, and to make clear to patients the potential benefits of preventing abdominal obesity.


STUDY TWO:
Title: Effect of Low Doses of N-3 Fatty Acids on Cardiovascular Diseases in Post-MI Patients
Trial Sponsor: Netherlands Heart Foundation, The Hague, The Netherlands, National Institutes of Health, Unilever
Year Presented: 2010
Summary Posted: 09/08/2010

Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca, Heartscape, Eisai, Sanofi Aventis, The Medicines Company, Ethicon, Bristol Myers Squibb Cogentus, PLx Pharma, Takeda


Description:
The goal of the trial was to evaluate treatment with supplemental omega-3 fatty acids (N-3) among patients with prior myocardial infarction (MI). Fatty acids in fish are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), whereas fatty acids in plants are alpha-linolenic acid (ALA).

Hypothesis:
Omega-3 fatty acids will be more effective at reducing major adverse cardiovascular events.

Drugs/Procedures Used:
Patients who had suffered an MI within the last 4 years were randomized to one of four margarines for dietary consumption: 1) EPA-DHA 400 mg daily + ALA placebo (n = 1,192), 2) EPA-DHA placebo + ALA 2 g daily (n = 1,197), 3) EPA-DHA 400 mg daily + ALA 2 g daily (n = 1,212), or 4) EPA-DHA placebo + ALA placebo (n = 1,236).

Concomitant Medications:
At baseline in the EPA-DHA + ALA group, the use of lipid-lowering drugs was 87%.

Principal Findings:
Overall 4,837 patients were randomized. In the EPA-DHA + ALA group, the mean age was 69 years, 22% were women, 20% were diabetic, systolic blood pressure was 141 mm Hg, and body mass index was 28 kg/m2. Compliance with study medication was verified by measurement of serum fatty acids.

The primary outcome, major adverse cardiovascular events (MACE), was similar between the EPA-DHA group and placebo group (hazard ratio [HR] 1.01, p = 0.93) and between the ALA group and placebo group (HR 0.91, p = 0.20). Among women in the ALA group, there was a nonsignificant reduction in the primary outcome (HR 0.73, p = 0.07) and among diabetics in the ALA group, there was a significant reduction in ventricular arrhythmia-related adverse events (HR 0.39, p = 0.002).

Interpretation:
Among patients with prior MI, dietary supplementation of omega-3 fatty acids was not beneficial since this therapy did not reduce MACE. Subgroup analysis revealed a nonsignificant reduction in MACE among women treated with ALA, and a significant reduction in ventricular arrhythmia-related adverse events among diabetics treated with ALA. Both of these subgroups should be interpreted with caution until further analysis can be performed. We continue to use FISH Oil capsules in patients that have very high triglycerides >500). The patients need follow up lipid evaluations as the LDL CAN UP AS MUCH AS 20% in patients taking fish oil. Most side effects are tolerable. Patients who get GERD with fish oil capsules might benefit from freezing the capsules.

Steven Almany, MD