Supplementation with Vitamin D and/or Omega-3 Fatty Acids
and Incidence of Heart Failure Hospitalization:
VITAL-Heart FailureThis section is compiled by Frank M. Painter, D.C.
Send all comments or additions to: Frankp@chiro.org
FROM: Circulation. 2019 (Nov 11) [Epub] ~ FULL TEXT
Luc Djoussé, MD, ScD; Nancy R. Cook, PhD; Eunjung Kim, MS; Vijaykumar Bodar, MD; Joseph Walter, BS, et. al
Department of Medicine,
Brigham and Women's Hospital and Harvard Medical School;
MAVERIC, Boston Veterans Affairs Healthcare System,
Boston, MA.
Among older adults, heart failure (HF) is the leading cause of hospitalization in the US and is associated with high costs and mortality. [1] Vitamin D and marine omega-3 (n-3) fatty acids have each been associated with reduced risks of HF in observational studies, but randomized trial evidence is limited. The current ancillary study sought to investigate the effects of vitamin D and n-3 supplements on the incidence of HF hospitalization in a large multi-ethnic cohort.
VITAL-HF is an ancillary study of the parent VITAL trial, which is a completed randomized trial with a two-by-two factorial design to examine the efficacy of vitamin D3 (2000 IU/d) and n-3 fatty acids (1 gram per day, including eicosapentaenoic acid [EPA, 460 mg] + docosahexaenoic acid [DHA, 380 mg]) for the prevention of cardiovascular disease and cancer in 25,871 adults from 2011 to 2017. Detailed description of the VITAL design and main results has been published. [2] We excluded 36 participants with prevalent HF for current analyses. Each participant signed informed consent and the study protocol was approved by the Institutional Review Board of Brigham and Women's Hospital.
Key Words: eicosapentaenoic acid; epidemiology; heart failure; diet
Clinical Trial Registration: URL: https://clinicaltrials.gov NCT01169259
Editorial Comment:
Once again big dollare are laid out by the National Institute of Health (NIH) to determine whether Omega 3 fatty acids can reduce the incidence of heart disease in the elderly.
Although anyone with a heart would agree that this is a worthy goal, the concept of prevention pre-supposes that one takes measures when it counts (like during early middle age), and not when the average participant is already (on average) 67.1 years old.
There was some good news from this study:Quote from: Vitamin D, fish oil fail to reduce first HF hospitalization risk“We found that neither vitamin D nor omega-3 significantly reduced the rate for first heart failure hospitalization, but omega-3 supplementation resulted in a statistically significant 14% reduction in the rate of recurrent heart failure hospitalizations, our secondary endpoint, compared with placebo,”
From the FULL TEXT Article:
Introduction
Among older adults, heart failure (HF) is the leading cause of hospitalization in the US and is associated with high costs and mortality. [1] Vitamin D and marine omega-3 (n-3) fatty acids have each been associated with reduced risks of HF in observational studies, but randomized trial evidence is limited. The current ancillary study sought to investigate the effects of vitamin D and n-3 supplements on the incidence of HF hospitalization in a large multi-ethnic cohort.
VITAL-HF is an ancillary study of the parent VITAL trial, which is a completed randomized trial with a two-by-two factorial design to examine the efficacy of vitamin D3 (2000 IU/d) and n-3 fatty acids (1 gram per day, including eicosapentaenoic acid [EPA, 460 mg] + docosahexaenoic acid [DHA, 380 mg]) for the prevention of cardiovascular disease and cancer in 25, 871 adults from 2011 to 2017. Detailed description of the VITAL design and main results has been published. [2] We excluded 36 participants with prevalent HF for current analyses. Each participant signed informed consent and the study protocol was approved by the Institutional Review Board of Brigham and Women’s Hospital.
First hospitalization for HF after randomization was the primary outcome and recurrent hospitalization for HF was a pre-specified secondary outcome. HF hospitalization was defined using the ACC/AHA definition [3] and required that ALL of the following criteria be met:(a) admission to a hospital due to HF;
(b) new or worsening symptoms due to HF on presentation;
(c) at least two physical signs or one physical sign plus at least one laboratory criterion obtained within 24 hours of presentation;
(d) patient received initiation or intensification of HF treatment.Each medical record was independently reviewed by at least two physician adjudicators and in the case of discrepancy, a third physician served as tie breaker [confirmation rate of self-reported HF was 37% (106 confirmed HF cases /285 medical records reviewed)]. We also queried data from the Centers for Medicare and Medicaid Services (CMS) using ICD-9 codes 398.91, 402.01-402.91, 404.01-404.93, and 428.0-428.90 in any position to further capture incident HF hospitalization. A sensitivity of 57% and specificity of 87% for using ICD 9 codes at any position in CMS data to ascertain HF and good agreement between ICD diagnosed HF and chart review (Kappa 0.92) have been reported [4]. We used Cox proportional hazards models to calculate hazard ratios and 95% CI for the primary outcome using the intention-to-treat approach and the Andersen-Gill model [5] with a robust variance which allows for varying numbers of events per person with different time between events for the secondary outcome.
The mean age at randomization was 67.1 (SD=7.1) years and 50.6% were women. During a median follow-up of 5.3 years, first HF hospitalization occurred in 499 (106 confirmed via review of medical records and 393 using CMS query) participants (240 events in the vitamin D group and 259 events in the placebo; hazard ratio: 0.93 (95% CI: 0.78 to 1.11), p=0.41 and 244 in the n-3 group and 255 in the placebo group; hazard ratio, 0.96 (95% CI: 0.80 to 1.14), p=0.61] (Figure 1).
Using 106 confirmed HF cases alone yielded similar results [HR: 1.12 (95% CI: 0.77 to1.65) for vitamin D vs. placebo and 0.96 (95%CI: 0.66 to 1.41) for n-3 fatty acids vs. placebo]. In secondary analysis, recurrent rates of HF hospitalization were not different between vitamin D intervention (341 events) and placebo (364 events) [HR: 0.94 (95% CI: 0.81 to 1.09), p=0.44]; however, there was a significant reduction in recurrent HF hospitalization with marine n-3 supplementation (326 events) vs. placebo (379 events) [HR: 0.86 (95% CI: 0.74 to 0.998), p=0.048]. Few events were preceded by myocardial infarction (20/499 first and 45/705 recurrent HF).
Limitations of our study include insufficient statistical power to evaluate the efficacy of vitamin D or n-3 fatty acids on HF with preserved vs. reduced left ventricular ejection fraction. Furthermore, we lacked statistical power to detect smaller, yet clinically relevant effect sizes. It is possible that some of the HF events identified via CMS were misclassified; however, such misclassification is likely to be non-differential because of randomization and blinding, thus biasing results towards the null (no effect of either intervention on HF rate). We were not able to obtain medical records to validate all HF ascertained via CMS. However, a high agreement has been reported between HF ascertained in CMS using ICD-9 codes and review of medical records. [4] Strengths of this study include novel investigation of the roles of vitamin D and n-3 fatty acids on incidence of HF hospitalization; randomized design; large sample size; and standardized methods to adjudicate HF hospitalization.
In conclusion, interventions with vitamin D or n-3 fatty acid supplements did not significantly reduce first HF hospitalization rate. Exploratory analyses suggesting some benefits of n-3 fatty acids on recurrent HF hospitalization require confirmation in future trials.
Acknowledgments
We are indebted to study participants and staff for their commitment to the trial.
Sources of Funding
The current ancillary study was supported by grant R01HL131687 (L Djousse) from the National Heart, Lung, and Blood Institute, Bethesda MD. The parent VITAL was supported by grants U01 CA138962 and R01 CA138962 from the national Institutes of Health, the Office of Dietary Supplements.
Dr. Mora was supported by the research grants from the National Heart, Lung, and Blood Institute (R01HL134811 and K24 HL136852). The funding sources had no role in the design and conduct of this study or the interpretation of the data. The opinions expressed in the manuscript are those of the study authors.
Disclosures
Pharmavite LLC of Northridge, California (vitamin D) and Pronova BioPharma of Norway and BASF (Omacor fish oil) donated the study agents, matching placebos, and packaging in the form of calendar packs. Quest Diagnostics (San Juan Capistrano, CA) measured serum 25-hydroxyvitamin D and serum omega-3 index at no cost to the study.
In the past years, Dr. Djousse received investigator-initiated grants from Amarin Inc and Merck. Dr. Mora received research grant support from Atherotech Diagnostics and the NIH and has served as consultant to Quest Diagnostics. Other co-authors have nothing to disclose.
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Circulation. 2019;139:e56-e528.Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Gordon D, Copeland T, D'Agostino D, et al.
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N Engl J Med. 2019;380:33-44.Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A, Fonarow GC, Jacobs JP, Jaff MR, Lichtman JH, et al.
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J Am Coll Cardiol. 2015;66:403-469.Kucharska-Newton AM, Heiss G, Ni H, Stearns SC, Puccinelli-Ortega N, Wruck LM, Chambless L.
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