Nutraceuticals and Cardiovascular Disease: Are we fishing? ACC - - PowerPoint PPT Presentation

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Nutraceuticals and Cardiovascular Disease: Are we fishing? ACC - - PowerPoint PPT Presentation

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Nutraceuticals and Cardiovascular Disease: Are we fishing? ACC Rockies 2013 March 20,2013 Sheri L. Koshman BScPharm, PharmD, ACPR Assistant Professor, Division of Cardiology, University of Alberta sheri.koshman@ualberta.ca Conflicts of

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Nutraceuticals and Cardiovascular Disease: Are we fishing?

ACC Rockies 2013

March 20,2013

Sheri L. Koshman BScPharm, PharmD, ACPR Assistant Professor, Division of Cardiology, University

  • f Alberta

sheri.koshman@ualberta.ca

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Conflicts of Interest

  • none
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Overview

  • General supplement use
  • Impact of supplements in CV disease:

– Multivitamins – Fish oils – Calcium

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“Let food be thy medicine, and medicine be thy food”

Hippocrates (460-377BC)

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How many of your patients use supplement?

  • 1. 10%
  • 2. 20%
  • 3. 50%
  • 4. 80%
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42% 53%

NCHS Data Brief 2011: 61

$27 Billion

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Number of Supplement

Bailey RL. J Nutr 2011;141(2):261-66

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Types of supplements

Prasad K, et al. Am J Cardiol 2013;111:339-45

n = 1,055

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Supplements: Impact

  • Lack of evidence regarding safety and efficacy

– Food vs drug classification

  • Beliefs about beneficial effects of supplements:

– May be less likely to engage in other preventative health behaviors – May be less likely to engage in modern, proven medical therapies

  • Adherence

– Pill burden – Financial burden

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Multivitamins

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Multivitamins

30% 39%

NCHS Data Brief 2011: 61

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Multivitamins

  • Observational data; sparse and inconsistent

– Nurses’ Health Study

  • RR 0.76 (95% CI 0.65-0.90)

– Swedish case-control

  • male RR 0.79 (0.63-0.98)
  • female RR 0.66 (0.48-0.91)

– PHS I – no association – WHI – no association – Multiethnic cohort study – no association

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JAMA 2012;308(17)1751-60

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Methodology

  • Randomized, DB, PC, 2 x 2 x 2 x 2 factorial

– Multivitamin (Centrum Silver) daily – Vitamin E 400IU q2d (ended 2007) – Vitamin C 500mg daily (ended 2007) – Beta-carotene 50mg q2d (ended 2003)

  • Outcomes:

– Prevention of CV disease – Cancer – Eye disease – Cognitive decline

JAMA 2012;308(17)1751-60

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Methodology

  • n=14,641
  • Male, physicians, > 50 years
  • 1999 thru August 2012
  • Follow-up: >98%; median 11.2 years
  • Outcomes:

– Primary: major CV events (non-fatal MI, non-fatal stroke, CVD mortality) – Other: total MI, total stroke, total mortality

JAMA 2012;308(17)1751-60

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JAMA 2012;308(17)1751-60 Middle age Regular Exercise Regular ASA Regular fruit/veg Few CVD risk factors

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JAMA 2012;308(17)1751-60

Results

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Conclusions

  • No effect of multivitamins on any CV outcome
  • Limited generalizability:

– Male, caucasian, physicians – “healthy” – good nutritional status at baseline

  • Lack of incremental benefit
  • Small benefit in the prevention of cancer

JAMA 2012;308(17)1751-60

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Results: Cancer

JAMA 2012;308(18):1871-80 No difference in cancer mortality Effect the same for secondary prevention

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Fish Oils

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Fish oils: Biologic effects

  • Anti-inflammatory
  • Anti-atherogenic
  • Anti-thrombotic
  • Anti-arrhythmic
  • Lower BP
  • Lower TG
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JAMA 2012;308(12):1024-33

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Methodology

  • RCT
  • Omega-3 PUFA supplementation in adults
  • Diet or supplements

– compared to another diet or placebo

  • Primary or secondary CVD
  • Treatment > 1 year
  • Result: 20 studies, 68,680 patients

JAMA 2012;308(12):1024-33

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JAMA 2012;308(12):1024-33

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JAMA 2012;308(12):1024-33

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Results

No difference: mixed vs. secondary prevention vs. ICD, blinding status or dose

JAMA 2012;308(12):1024-33

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JAMA 2012;308(12):1024-33

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Conclusions

  • No significant effect on major CV outcomes

across patient populations at increase CV risk

  • Larger effects seen pre-statin era
  • Lack of incremental benefit on top of modern

medical therapy

  • Similar results

– Kwak et al. Arch Intern Med 20012;172:686-94

  • limited to secondary prevention, placebo controlled only

– Kotwal et al. Circ Cardiovasc Qual Outcomes 2012;5:808-18

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Fish Oils

Courtesy of Elizabeth Woo, RD

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Calcium

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Calcium

NCHS Data Brief 2011: 61

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Calcium

  • Calcium is essential for many biological actions
  • Historical data suggested that dietary calcium

may be protective against CV disease

  • More recent data suggests that calcium

supplementation may increase the risk of CV disease

  • No prospective RCTs to date have investigated the

role of calcium supplementation of CV as a primary endpoint

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BMJ 2010;341:c3691doi10.1136/bmj.c3691 Patient and trial level data RCT, PC, calcium > 500mg/d (without Vit D) n=11 trials (12,000) Median follow-up: 3.6 years

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BMJ 2010;341:c3691doi10.1136/bmj.c3691

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BMJ 2011;342:d2040doi:10.1136/bmj.d2040

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Methodology

  • WHI reanalysis (n=36,282):

– Sub-group analysis of personal use versus no personal use

  • 54% of participant were taking personal calcium
  • 47% of participant were taking personal vitamin D

– Hypothesis: frequent personal use obscured adverse CV outcomes

  • Meta-analysis

– Calcium +/- vitamin D use – update previous analysis with WHI and non-users of personal calcium at randomization

BMJ 2011;342:d2040doi:10.1136/bmj.d2040

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Results: Reanalysis

HR 1.22-1.13 HR 0.83-1.08 Significant interaction with personal use, but not Vitamin D or dietary calcium BMJ 2011;342:d2040doi:10.1136/bmj.d2040 * * *

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BMJ 2011;342:d2040doi:10.1136/bmj.d2040

Calcium + Vitamin D vs. Placebo

n=20,090 No significant effect on all cause mortality

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BMJ 2011;342:d2040doi:10.1136/bmj.d2040

Effect of supplementation (Calcium +/- Vit D): Patient-level data (n=24,869)

“Treating 1000 people with calcium or calcium + vitamin D x 5 years, would cause 6 additional MIs or stroke and prevent 3 fractures” NNH = 240 NNH = 283 NNH = 178

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Effect of supplementation: trial-level data (n=28,072)

BMJ 2011;342:d2040doi:10.1136/bmj.d2040

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BMJ 2013;346:f228 doi:10.1136/bmj.f228

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Methodology

  • Swedish mammography cohort, n=90,303
  • Cohort 1987- 90 (n = 61,433)

– 1997 (n=38,984)

  • Expanded dietary questionnaire
  • Supplement questionnaire
  • Categorized intake:

– <600mg – 600-999mg – reference range, RDA in Sweden 800mg – 1000-1399mg – >1400mg

  • Follow-up (100%):

– Median 19 yrs (1,094,880 person yrs) – Primary: death – Secondary: CV disease, IHD, and stroke

BMJ 2013;346:f228 doi:10.1136/bmj.f228

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<600mg HR 1.38 (1.27-1.51) >1400mg HR 1.40 (1.17-1.67) <600mg HR 1.63(1.42-1.87) >1400mg HR 1.49 (1.09-2.02) <600mg HR 1.65 (1.36-2.01) >1400mg HR 2.14 (1.48-3.09) <600mg HR 1.50 (1.14-1.97) >1400mg HR 0.73 (0.33-1.65) BMJ 2013;346:f228 doi:10.1136/bmj.f228

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BMJ 2013;346:f228 doi:10.1136/bmj.f228

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25% of cohort, 75% multivitamin (120mg calcium) (500mg) BMJ 2013;346:f228 doi:10.1136/bmj.f228

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Conclusions

  • High dietary intake of calcium is associated

with increase in mortality and CV events

  • High dietary intake + calcium tablets is

associated with higher mortality

  • Limitations:

– Cohort design – Questionnaire reliability – Healthy user bias

BMJ 2013;346:f228 doi:10.1136/bmj.f228

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JAMA Intern Med. doi:10.1001/jamainternmed.2013.3283

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Methodology

  • NIH-AARP diet and Health Study, US 1995-96
  • Age 50-71

– Men (n=219,059) – Women (n=169,170)

  • Baseline

– Dietary intake (quintiles) – Frequency and dosage of calcium supplements – Multivitamin intake

  • An interaction by sex was found and therefore analysis was done

separately

  • Follow-up:

– 12 years – 3,549,364 person-years

JAMA Intern Med. doi:10.1001/jamainternmed.2013.3283

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Results

  • Calcium supplements:

– Men 23% – Women 56%

  • Multivitamins containing calcium

– Men 56% – Women 58%

JAMA Intern Med. doi:10.1001/jamainternmed.2013.3283

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Dietary Calcium

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Consistent when limited to calcium supplements and not multivitamins

Supplements

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CVD mortality RR 1.12 (1.04-1.20) HD mortality RR 1.12 (1.04-1.21) No association Men Women

Total Calcium

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Conclusions

  • Supplementary calcium, but not dietary

calcium is associated with increase CVD mortality in men, but not women.

  • Limitations:

– Cohort design – Duration of supplement use – Calcium intake only measured at baseline

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Key Points

  • Multivitamins

– Limited data to support the routine use of multivitamins – RCT data from healthy males indicated no benefit to supplementation

  • Fish oils

– Limited data to support routine use in prevention of CV disease, both primary and secondary prevention

  • Calcium

– Data remains inconclusive – Minimal effect in fracture prevention unlikely to outweigh the potential risk of CV disease