Fatty acids and cardiovascular health: current evidence and next steps Emanuele Di Angelantonio, MD, PhD Department of Public Health and Primary Care
NICE guidelines on fatty acids Eliminate the use of trans fats for human consumption and encourage the use of vegetable oils high in polyunsaturated and monounsaturated fatty acids to replace oils containing trans fats. Reduce population level consumption of saturated fat People should not routinely be recommended to take omega-3 fatty acid supplements for the primary prevention of cardiovascular disease National Institute for Health and Care Excellence (NICE) public health guidance 25 (2010)
What is the current evidence evidence on fatty acids and coronary heart disease? Fatty Acids Coronary heart disease Our systematic review and meta-analysis of the published literature aimed to quantify three aspects of the evidence on fatty acids and coronary heart disease (CHD): self-reported dietary fatty acid intake individual fatty acid biomarkers randomized controlled trials
Self-reported dietary fatty acid intake and coronary outcomes Studies, n Participants, n Events, n Risk Ratio (95% CI) Dietary fatty acids intake Total saturated fatty acids 20 276 763 10 155 1.03 (0.98-1.07) Total monounsaturated fatty acids 9 144 219 6031 1.00 (0.91-1.10) ω-3 fatty. acids α-linolenic 7 157 258 7431 0.99 (0.86-1.14) Total long-chain ω-3 16 422 786 9089 0.87 (0.78-0.97) Total ω-6 fatty acids 8 206 376 8155 0.98 (0.90-1.06) Total trans fatty acids 5 155 270 4662 1.16 (1.06-1.27) 0.75 1 1.25 1.50 RR (95% CI) Comparing Top vs. Bottom Thirds of Baseline Dietary Fatty Acid Intake Chowdhury R, Ann Intern Med 2014
Fatty acid biomarkers and coronary outcomes Circulating fatty acids composition Studies, n Participants, n Events, n Risk Ratio (95% CI) Total saturated fatty acids 14:0, Myristic 15:0, Pentadecanoic 8 5 4 15 590 10 598 5490 3758 2932 2283 1.06 (0.86-1.30) 0.96 (0.83-1.12) 0.94 (0.67-1.32) 16:0, Palmitic 17:0, Margaric 15:0, Pentadecanoic + 17:0, Margaric 10 4 4 25 554 5490 5490 4318 2283 2283 1.15 (0.96-1.37) 0.77 (0.63-0.93) 0.81 (0.62-1.06) 18:0, Stearic 8 22 266 3654 1.23 (0.93-1.61) Total trans fatty acids 4 7661 2389 1.05 (0.76-1.44) 18:1, trans-oleic 2 921 380 1.20 (0.39-3.73) 18:2, trans-linoleic 2 921 380 1.36 (0.83-2.22) 0.50 0.75 1 1.25 1.50 2.00 RR (95% CI) Comparing Top vs. Bottom Thirds Chowdhury R, Ann Intern Med 2014
Fatty acid biomarkers and coronary outcomes Circulating fatty acids composition Studies, n Participants, n Events, n RR (95% CI) Total monounsaturated fatty acids 6 14 356 3236 1.06 (0.97-1.17) 16:1n-7, Palmitoleic 9 17 927 4127 0.96 (0.86-1.08) 18:1cis-9, Oleic 9 22 664 3687 1.09 (0.97-1.23) ω-3 polyunsaturated fatty acids 18:3n-3, α-linolenic 8 14 945 3426 0.93 (0.83-1.03) Total long-chain ω-3 4 10 558 2753 0.84 (0.63-1.11) 20:5n-3, Eicosapentaenoic 13 23 065 4624 0.78 (0.65-0.94) 22:6n-3, Docosahexaenoic 13 23 065 4624 0.79 (0.67-0.93) 20:5n-3, Eicosapentaenoic + 22:6n-3, Docosahexaenoic 13 20 809 4073 0.75 (0.62-0.89) 22:5n-3, Docosapentaenoic 4 7155 2565 0.64 (0.47-0.89) Total ω-6 polyunsaturated fatty acids 18:2n-6, Linoleic 18:3n-6, γ-linolenic 2 10 4 7432 23 022 8285 1877 3866 2259 0.94 (0.84-1.06) 0.99 (0.77-1.28) 1.03 (0.90-1.17) 20:2n-6, Eicosadienoic 2 4029 1689 1.18 (0.93-1.50) 20:3n-6, Dihomo- γ -linolenic 20:4n-6, Arachidonic 6 10 14 189 22 948 3214 3739 1.11 (0.93-1.33) 0.83 (0.74-0.92) 22:4n-6, Docosatetraenoic 22:5n-6, Docosapentaenoic 2 2 4029 4029 1689 1689 1.20 (0.99-1.45) 0.97 (0.50-1.88) 0.50 0.75 1 1.25 1.50 2.00 RR (95% CI) Comparing Top vs. Bottom Thirds Chowdhury R, Ann Intern Med 2014
Randomized controlled trials of fatty acids and coronary outcomes Fatty Acid Studies, n Events/Participants, n/n Intervention Group Control Group Risk Ratio (95% CI) α-linolenic acid 4 199/9444 220/9422 0.97 (0.69-1.36) Long-chain ω-3 fatty acid 17 2426/38 303 2548/38 277 0.94 (0.86-1.03) ω-6 fatty acid 8 459/7245 515/7231 0.86 (0.69-1.07) 0.75 Intervention Better 1.00 1.25 1.50 Control Better Chowdhury R, Ann Intern Med 2014
What is the current evidence evidence on fatty acids and coronary heart disease? Fatty Acids Coronary heart disease Lipids level
Self-reported dietary fatty acid intake and lipids level Replacement of dietary calories from saturated fat by polyunsaturated fat leads to small, but potentially important, reductions in low-density lipoprotein cholesterol concentration. Clarke R et al. BMJ 1997;314:112
Cholesterol levels and coronary heart disease Observational epidemiology Pharmacological inhibition (statin trials) 3.0 2.5 Risk of coronary heart disease 2.0 1.5 Risk reduction of coronary heart disease 1.0 2 3 4 5 6 7 Usual Mean LDL-c (mmol/l) Reduction in LDL cholesterol (mmol/l) CTT, Lancet 2005 ERFC, JAMA 2009 National Institute for Health and Care Excellence (NICE) public health guidance 25 (2010)
How can we better understand the association between fatty acids and coronary heart disease? Fatty Acids Coronary heart disease Powerful prospective studies measuring large and uniform panels of individual fatty acids biomarkers and self-reported dietary intake
Large-scale multi-cohort observational: EPIC-CVD 520k participants in 10 countries 25k new-onset CVD cases 15k controls Assays 650k common and uncommon SNPs 75 soluble biomarkers (including 37 fatty acids) Detailed questionnaire lifestyle dietary factors Danesh et al., Eur J Epidemiol 2007
How can we better understand the association between fatty acids and coronary heart disease? Fatty Acids Coronary heart disease Powerful prospective studies measuring large and uniform panels of individual fatty acids biomarkers and self-reported dietary intake Mendelian randomisation: use of genotype-disease associations to make causal inferences about modifiable risk factors for disease
Judging causality by integrative analyses Mendelian randomisation Aim: Randomised trial To evaluate the effects of treatments Mendelian randomisation To distinguish between causal and non-causal risk factors Sample Population Randomisation Random allocation of alleles Intervention Control Genotype aa Genotype AA Biomarker lower Biomarker higher Biomarker lower Biomarker higher Disease rate lower Disease rate higher Disease rate lower Disease rate higher Hingorani et al, Lancet 2005
How can we better understand the association between fatty acids and coronary heart disease? Fatty Acids Coronary heart disease Powerful prospective studies measuring large and uniform panels of individual fatty acids biomarkers and self-reported dietary intake Mendelian randomisation: use of genotype-disease associations to make causal inferences about modifiable risk factors for disease Large randomized controlled trials in primary prevention settings
Conclusions Current evidence is not clearly supportive (or dismissive) of the present recommendations based on composite fatty acids Findings however suggest that the effects of various individual fatty acids within the same composite fatty acid family may vary Therefore, to help inform future public health nutrition guidelines, further large-scale epidemiologic and intervention evidence are needed to characterise effects of specific fats (and their food sources) on coronary risk in greater detail.