Elsevier

American Heart Journal

Volume 164, Issue 6, December 2012, Pages 902-909.e2
American Heart Journal

Clinical Investigation
Congestive Heart Failure
Vitamin D reduces left atrial volume in patients with left ventricular hypertrophy and chronic kidney disease

https://doi.org/10.1016/j.ahj.2012.09.018Get rights and content

Background

Left atrial enlargement, a sensitive integrator of left ventricular diastolic function, is associated with increased cardiovascular morbidity and mortality. Vitamin D is linked to lower cardiovascular morbidity, possibly modifying cardiac structure and function; however, firm evidence is lacking. We assessed the effect of an activated vitamin D analog on left atrial volume index (LAVi) in a post hoc analysis of the PRIMO trial (clinicaltrials.gov: NCT00497146).

Methods and results

One hundred ninety-six patients with chronic kidney disease (estimated glomerular filtration rate 15-60 mL/min per 1.73m2), mild to moderate left ventricular hypertrophy, and preserved ejection fraction were randomly assigned to 2 μg of oral paricalcitol or matching placebo for 48 weeks. Two-dimensional echocardiography was obtained at baseline and at 24 and 48 weeks after initiation of therapy. Over the study period, there was a significant decrease in LAVi (−2.79 mL/m2, 95% CI −4.00 to −1.59 mL/m2) in the paricalcitol group compared with the placebo group (−0.70 mL/m2 [95% CI −1.93 to 0.53 mL/m2], P = .002). Paricalcitol also attenuated the rise in levels of brain natriuretic peptide (10.8% in paricalcitol vs 21.3% in placebo, P = .02). For the entire population, the change in brain natriuretic peptide correlated with change in LAVi (r = 0.17, P = .03).

Conclusions

Forty-eight weeks of therapy with an active vitamin D analog reduces LAVi and attenuates the rise of BNP. In a population where only few therapies alter cardiovascular related morbidity and mortality, these post hoc results warrant further confirmation.

Section snippets

Study population

The PRIMO study enrolled 227 patients from 60 centers in 11 countries between July 2008 and September 2010. Details of the protocol and primary results have been reported previously.26 In brief, patients were 18 to 75 years old with LV hypertrophy on 2-dimensional transthoracic echocardiography (septal wall thickness of 1.1-1.7 cm in females, 1.2-1.8 cm in males),27 LV ejection fraction (LVEF) >50%, and estimated glomerular filtration rate (eGFR) of 15 to 60 mL/minute per 1.73m2. Patients on

Baseline characteristics

A total of 196 (86%) of the 227 enrolled patients in the PRIMO study had available longitudinal echocardiographic data; 103 were randomly assigned to paricalcitol; and 93, to placebo. Baseline characteristics were similar between groups (Table I). Participants were mostly white males with hypertension. Other cardiovascular risk factors, such as obesity and diabetes mellitus, were highly prevalent in both groups. Most participants were receiving RAAS inhibitors (79% in paricalcitol vs 80% in

Discussion

The nephrology community has long sought interventions to modify cardiac structure and function given the marked elevation in risk for cardiovascular disease and the almost universal findings of altered cardiac structure and function in this population. In this post hoc analysis of the PRIMO trial, we demonstrate that paricalcitol therapy over 48 weeks was associated with a significant decrease in LAVi in patients with CKD, despite similar blood pressure control and superimposed RAAS inhibitor

Disclosures

Dr. Thadhani received a coordinating grant from Abbot Laboratories to the Massachusetts General Hospital, speaker's fees and travel support from Abbot Laboratories. Drs. Pritchett, Andress, and Zhang are employees of Abbott Laboratories and may own Abbott stock or options. Drs. Agarwal, Zoccali, Wanner and Zehnder received honoraria from Abbott Laboratories for lectures or for participation in steering committee. Dr. Manning received travel support for a CMR meeting from Abbott Laboratories.

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