Food and plant bioactives for reducing cardiometabolic disease: How does the evidence stack up?

Transcription

1 Food and plant bioactives for reducing cardiometabolic disease: How does the evidence stack up? Arrigo F.G. Cicero, MD, PhD Medical and Surgical Sciences Dept., University of Bologna, Italy Italian Nutraceutical Society (SINut)

2 The cardiovascular disease paradox The leading cause of mortality in Western countries We know the most part of risk factors Life-style improvement has proven to decrease the CV disease risk However, we fail to improve CV risk profile of general population Why??? Lancet. 2016;387(10033):

3 Responsabilities of a world-wide failure General population Wrong perception of risk factors Lack of will/difficulty to change life-style Lack of knowledge on how to change life-style Lack on confidence on the efficacy of life-style improvement Experts Wrong perception of risk factors Lack of knowledge on what is really efficacious Lack of confidence in general population will to change Scientific messages often far from practical application

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5 Recommendation for cost-effective prevention of cardiovascular disease 5

6 CV risk related to the most common risk factors (%): data from the EURIKA survey Gyakkkar et al., BMC Public Health 2011; 11:704

7 Stroke Mortality (floating absolute risk and 95% CI) IHD Mortality (floating absolute risk and 95% CI) CHD and CVD mortality by usual SBP Age at risk: ys ys ys ys Age at risk: ys ys ys ys ys Usual Systolic Blood Pressure (mmhg) Usual Systolic Blood Pressure (mmhg) Prospective Studies Collaboration. Lancet 2002;360:

8 Cannon CP et al. NEJM 2015; 372(25): Meta-regression of results from large on LLDs: Change in LDL-C vs Clinical Benefit

9 What data we need to state that a food, food component or plant extract modifies the CVD risk? - Epidemiological data - Biochemistry/Pharmacology - Pharmacokinetic data - Double-blind randomized clinical trials - Meta-analyses of RCTs - Open studies in clinical practice/every day life - Intermediate/Hard outcomes

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12 The dosages 1500 mg/day for 9 months (6 tablets/day!)

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14 FMD and CVD risk: 1% increase = 12% less CVD risk! Matsusawa Y et al. J Am Heart Assoc. 2015;4(11): e

15 Beetroot and FMD: a metaanalysis of RCTs Lara J et al. Eur J Nutr. 2016;55(2):451-9

16 Changes in endothelial reactivity and arterial stiffness parameters during the trial Baseline/end wash-out End of treatment Low LTP2 High LTP2 Low LTP2 High LTP2 Pulse Wave Velocity (m/s) 9,5±1,9 9,7±2,1 9,6±2,0 9,5±1,3 Augmentation Index (%) 24,5±2,6 26,0±3,5 25,7±2,7 25,6±3,1 Pulse volume changes (%) 65,4±6,1 63,9±6,3 64,3±6,6 68,1±4,2* *P<0,05 vs. baseline, P<0,05 vs. Low LTP2 Cicero AF et al. Data on file +4.1%!!!

17 RR and 95%CI for high PWV and clinical events: A= CV events B= CV mortality C= Total mortality An increase in PWV by 1 m/s corresponds with an increase of 12%, 13%, and 6% in total CV events, CV mortality, and all-cause mortality, respectively. Charalambos Vlachopoulos et al. Hypertension. 2012;60:

18 Effects of n-3 PUFAs on PWV: a meta-analysis of RCTs Pase MP et al. Br J Nutr. 2011;106(7):974-80

19 Delta PWV (m/s) RYR-CoQ10 middle-term effect on cfpwv Cicero et al. Ann Nutr Metab. 2016;68(3):213-9 Cicero et al. Ann Nutr Metab. 2016;68(3):213-9

20 Garnet L. Anderson, PhD The COcoa Supplement and Multivitamin Outcomes Study (COSMOS): A Randomized Trial of Cocoa Flavanols and Multivitamins in the Prevention of CVD and Cancer JoAnn E. Manson, MD, DrPH Howard D. Sesso, ScD, MPH Brigham and Women's Hospital Harvard Medical School

21 The COSMOS Trial design

22 NNT= 23 NNT= 18 China Coronary Secondary Prevention Study NNT= 82 NNT= patients in secondary prevention 1,445 aged 65 to 75 7 years follow-up NNT= 51 NNT= 23 Adult patients Elderly patients Ye et al. J Am Geriatr Soc 2007;55:

23 MACE CoQ10 and main outcomes in HF: The Q- SYMBIO study DEATH Mortensen SA et al. JACC Heart Fail. 2014;2(6):641-9.

24 Long-term effectiveness and safety of a combined nutraceutical based approach to reduce cholesterolemia in statin intolerant subjects with and without metabolic syndrome Cicero et al. Am J Cardiol. 2010;105(10):1504.

25 Martí-Carvajal AJ et al. Cochrane Database of Systematic Reviews 2015; 1: CD What does not function? Vitamin B for HCYS reduction The risk of MI is similar to placebo

26 Do we really need health claims based on data obtained from healthy subjects? 1. Patients with IBD or other chronic GI disorders (5-10% of the general population) 2. Elderly subjects (15-20% of general population) 3. Chronic Kidney Disease patients (10-15% of general population) 4. Patients assuming drugs with narrow therapeutic ranges (Warfarin, Immunosuppressants, HAART, )

27 And a couple of practical problems TASTE DOSES COST PERSISTENCE EFFECTIVE PREVENTION

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