BackgroundPatients with peripheral artery disease (PAD) experience significant morbidity and mortality. The OMEGA-PAD I Trial, a randomized, double-blinded, placebo-controlled trial, addressed the hypothesis that short-duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves endothelial function and inflammation in PAD.Methods and ResultsEighty patients with stable claudication received 4.4 g of fish oil or placebo for 1 month. The primary end point was endothelial function as measured by brachial artery flow-mediated vasodilation. Secondary end points included biomarkers of inflammation, n-3 polyunsaturated fatty acids metabolome changes, lipid profile, and walking impairment questionnaires. Although there was a significant increase in FMD in the fish oil group following treatment (0.7±1.8% increase from baseline, P=0.04), this response was not different then the placebo group (0.6±2.5% increase from baseline, P=0.18; between-group P=0.86) leading to a negative finding for the primary endpoint. There was, however, a significant reduction in triglycerides (fish oil: −34±46 mg/dL, P<0.001; placebo −10±43 mg/dL, P=0.20; between-group differential P-value: 0.02), and an increase in the omega-3 index of 4±1% (P<0.001) in the fish oil group (placebo 0.1±0.9%, P=0.49; between-group P<0.0001). We observed a significant increase in the production of pathway markers of specialized pro-resolving mediators generated from n-3 polyunsaturated fatty acids in the fish oil group.ConclusionsHigh-dose, short-duration fish oil supplementation did not lead to a different response in the primary end point of endothelial function between the treatment and placebo group, but improved serum triglycerides and increased the production of downstream n-3 polyunsaturated fatty acids–derived products and mediators in patients with PAD.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov/. Unique identifier: NCT01310270.

Introduction Sedentarism, also termed physical inactivity, is an independent risk factor for cardiovascular diseases. Mechanisms thought to be involved include insulin resistance, dyslipidemia, hypertension, and increased inflammation. It is unknown whether changes in vascular and endothelial function also contribute to this excess risk. We hypothesized that short-term exposure to inactivity would lead to endothelial dysfunction, arterial stiffening and increased vascular inflammation. Methods Five healthy subjects (4 males and 1 female) underwent 5 days of bed rest (BR) to simulate inactivity. Measurements of vascular function [flow-mediated vasodilation (FMD) to evaluate endothelial function; applanation tonometry to assess arterial resistance], inflammation and metabolism were made before BR, daily during BR and after 2 recovery days. Subjects maintained an isocaloric diet throughout. Results Bed rest led to significant decreases in brachial artery and femoral artery FMD [Brachial: 11 ± 3% pre-BR vs. 9 ± 2% end-BR, P=0.04; Femoral: 4 ± 1% vs. 2 ± 1%, P=0.04]. The central augmentation index increased with BR [−4 ± 9% vs. 5 ± 11%, P=0.03]. Diastolic blood pressure (DBP) increased [58 ± 7 mmHg vs. 62 ± 7 mmHg, P=0.02], while neither systolic blood pressure nor heart rate changed. 15-HETE, an arachidonic acid metabolite, increased but the other inflammatory and metabolic biomarkers were unchanged. Conclusions Our findings show that acute exposure to sedentarism results in decreased endothelial function, arterial stiffening, increased DBP, and an increase in 15-HETE. We speculate that inactivity promotes a vascular “deconditioning” state characterized by impaired endothelial function, leading to arterial stiffness and increased arterial tone. Although physiologically significant, the underlying mechanisms and clinical relevance of these findings need to be further explored.

Medication adherence is a major determinant of antiretroviral (ARV) treatment success and a significant challenge for HIV-positive patients, yet a well-defined adherence threshold to maintain virologic suppression on current ARV regimens remains unclear. The present study evaluated 1915 Kaiser Permanente Southern California HIV-positive patients on one of three regimen types: (1) emtricitabine-tenofovir-efavirenz (FTC-TDF-EFV); (2) emtricitabine-tenofovir (FTC-TDF) and raltegravir (RAL); and (3) FTC-TDF and a boosted protease inhibitor, either darunavir (DRV) or atazanavir (ATV), to compare virologic failure rates between patients with varying levels of adherence to the regimens. Medication possession ratios (MPRs) were calculated to determine adherence, and HIV RNA PCR levels drawn 12-18 months after the initial pharmacy claim for the measured drug were used to determine virologic failure, which was defined as two consecutive HIV RNA PCR measurements ≥200 copies/mL. Adherence was inversely related to virologic failure, with an 80-90% MPR threshold resulting in no more than 3.5% virologic failure rate. In comparison, ≥90% MPR yielded no more that 1.1% virologic failure rate. Although the gold-standard adherence threshold for older ARV regimens has been 95%, an 80-90% MPR appears sufficient to maintain virologic suppression in patients treated with these three ARV regimen types.

Objective Patients with peripheral artery disease (PAD) have varying degrees of walking disability that does not completely correlate with ankle brachial index (ABI) or angiographic anatomy. We hypothesized that endothelial function (EF) is an independent predictor of symptom severity in PAD patients. Methods This was a cross-sectional study of PAD (N=100) patients presenting to a vascular surgery clinic. All patients received ABI testing and brachial artery flow-mediated, endothelium-dependent, vasodilation (FMD) to assess arterial EF. Symptom severity and walking disability reported by Rutherford category was based on the patient’s self-report during clinic visit, recorded by the investigator-vascular surgeons. Demographic, biochemical and physiologic parameters were entered into regression equations to determine association with symptom severity. Results Mean age was 66 ± 8 and 43% had diabetes. Mean FMD was 7.4% indicating impaired EF. EF progressively declined as Rutherford category increased (p=0.01). Brachial artery FMD, ABI, systolic blood pressure, C-reactive protein, LDL, HDL, beta-blocker use and a history of diabetes or coronary artery disease (CAD) were all associated with Rutherford category (all p<0.05). After multivariable regression, EF (p<0.02) and ABI (p<0.0001) were independently associated with walking disability. When the cohort was restricted to claudicants (n=73), EF remained associated with walking disability after adjustment for other covariates (p=0.0001). Conclusion Symptom severity in PAD is multifactorial, reflecting both impaired hemodynamics and vascular dysfunction. This is the first report demonstrating that walking disability in PAD is associated with arterial EF. The mechanistic link underlying these observations remains to be defined.

Renal branch occlusion was by far the commonest late failure mode after multibranched endovascular aneurysm repair. The current study provides no basis for a change in patient selection or stent-graft design, only a change in the components used to construct renal branches. It is too early to tell the effect this will have.