Ongoing Saga of Homocysteine and Vasculopathy

SOURCE: Catena FC, et al. J Am Soc Hypertens 2015;9:167-175.

The relationship between homocysteine (hCYS) and vascular disease has been recognized for at least 2 decades. Indeed, the strength of the association between plasma hCYS levels and coronary atherosclerosis surpasses that of cholesterol. Once this relationship was publicized, a flurry of enthusiasm for modulation of hCYS ensued, based largely on the strong observational data and the simplicity with which hCYS can be lowered: supplementation with folate and B vitamins. Since these treatments are not associated with meaningful toxicity at appropriate doses, there appeared to be much to celebrate: an easy, inexpensive fix for an important health problem.

After a bevy of trials in which hCYS lowering failed to show risk reduction for cardiovascular events, need for revascularization, etc., one editorialist confidently announced “The homocysteine hypothesis is dead!”. Well, apparently some still feel a faint pulse.

Catena et al published their data looking at the relationship between hCYS and carotid disease among hypertensive patients. They found that carotid intima-media thickness was linearly related to hCYS levels, independent of age, blood pressure, and C-reactive protein.

Since no clinical trials have shown a favorable impact of hCYS modulation, why should clinicians care? The authors bring up the interesting proposition that since elevated hCYS is a recognized risk factor for vasculopathy, it might help influence treatment decisions for management of persons at risk for cardiovascular disease. Perhaps, for instance, elevated hCYS might tip the balance of a treatment decision for persons with a strong family history of vascular disease, but borderline risk factors (e.g., blood pressure, lipids, glucose).

Roflumilast for Acute Exacerbations in COPD

SOURCE: Martinez FJ, et al. Lancet 2015; 385:857-866.

Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are potentially highly consequential: In-hospital mortality is approximately 10%, and up to 25% of patients admitted to the ICU die. Additionally, AE-COPD is associated with a decline in pulmonary function that is not regained once the exacerbation is resolved. Fortunately, several of the tools we use to treat COPD are associated with reduced frequency of exacerbations.

Roflumilast (ROF) is a PDE-4 inhibitor that has been shown to reduce AE-COPD and has FDA labelling for that indication. Martinez et al have published the results of their multicenter randomized, double-blind, placebo-controlled trial that sought to determine whether ROF reduces exacerbations compared to placebo in severe COPD patients who are already on background combination therapy of inhaled long-acting beta-agonist plus inhaled corticosteroid (n = 1945).

After 1 year of treatment, the rate of AE-COPD was statistically significantly lower in persons who were treated with ROF than those receiving placebo. The adverse events rates were similar in the ROF and placebo groups. Additionally, hospital admissions for AE-COPD were significantly reduced in the ROF group vs placebo. The addition of ROF to the regimen of patients with severe COPD already using combination therapy with beta-agonists and inhaled corticosteroids can reduce exacerbations and hospitalizations related to exacerbations.

Treatment of OSA Reduces Risk of Repeat Revascularization After PCI

SOURCE: Wu X, et al. Chest 2015;1478:708-718.

Obstructive sleep apnea (OSA) is associated with numerous comorbidities and downstream consequences, not the least of which are increased cardiovascular events, hypertension, and arrhythmias. The increased sympathetic tone associated with OSA is usually considered a major culprit in the evolution of such adversities. Although the associations between OSA are strong and consistent across numerous reports and diverse populations, outcomes trials showing concrete endpoint reduction through successful treatment of OSA are less evident.

The clinical trial data reported by Wu et al confirm very favorable results in a very specific population: Persons with sleep laboratory-confirmed OSA (n = 390) who had undergone PCI were followed over 4.8 years (median). The primary endpoint of interest was whether treatment of OSA affected the incidence of revascularization compared to untreated OSA. Treatment of OSA by CPAP was confirmed at 3-monthly intervals for the first year, and annually thereafter.

The incidence of coronary revascularization was almost twice as high in the untreated OSA group than in the treated OSA group (26.1% vs 14.1%, P = 0.019). Although there were statistically significant differences between groups as far as overall mortality or cardiovascular events, outcomes at 5 years tended to favor the CPAP-treated OSA patients. OSA treatment reduces the need for revascularization in persons who have undergone PCI.