Plasma Omega-6 Fatty Acids and the Risk of Cardiovascular ...
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Figure 3: Adjusted OR per 1-SD increase of GLA. GLA remained significantly associated with a 16% reduced odds for CV death after multivariable adjustment. • Plasma gamma-linoleic acid content shows a significant association with the odds of CV death after ACS. • Other Ω6-PUFAs were not consistently associated with cardiovascular events. • Future research should examine whether dietary intake of GLA after ACS may help to attenuate CV risk. Figure 2: Unadjusted OR per 1-SD increase. GLA was significantly associated with a 28% reduced odds for CV death after Bonferroni-Holm correction (P B-H <0.001). Table 2: Spearman correlations (*P<0.01) LDL-C HDL-C TG hsCRP Ω6-PUFA 0.14* 0.18 -0.36* -0.05* GLA 0.06* 0.01 0.12* -0.14* Plasma Omega-6 Fatty Acids and the Risk of Cardiovascular Events in Patients after an Acute Coronary Syndrome: Insights from MERLIN-TIMI 36 Thomas A. Zelniker 1 , MD, MSc; David A. Morrow 1 , MD, MPH; Dariush Mozaffarian 2 , MD, DrPH; Jianping Guo 1 , MSc; Kyungah Im 1 , PhD; Marc S. Sabatine 1 , MD, MPH; Michelle O’Donoghue 1 , MD, MPH 1 TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School 2 Friedman School of Nutrition Science and Policy, Tufts University BACKGROUND RESULTS METHODS Disclosures : T.A. Zelniker: Research Grant; Significant; Deutsche Forschungsgemeinschaft (DFG ZE 1109/1-1). D.A. Morrow: Research Grant; Significant; Abbott Labs, Amgen, Astra Zeneca, BRAHMS, Eisai, GSK, Medicines Co, Merck, Novartis, Pfizer, Roche, Takeda. Consultant/Advisory Board; Modest; Abbott Labs, Astra Zeneca, InCardia, Peloton, Roche, Verseon. Consultant/Advisory Board; Significant; Aralez, Bayer. D. Mozaffarian: Research Grant; Significant; National Institute of Health and Gates Foundation. Honoraria; Significant; Acasti Pharma, GOED, DSM, Nutrition Impact, Pollock Communications, Bunge, Indigo Agriculture, Amarin. Consultant/Advisory Board; Significant; OMmada Health, Elysium Health, DayTwo. Other; Significant; Uptodate. J. Guo: None. K. Im: None. M.S. Sabatine: Research Grant; Significant; Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen Research and Development, Medicines Company, MedImmune, Merck, Novartis, Pfizer, Poxel, Takeda. Consultant/Advisory Board; Modest; AstraZeneca, CVS Caremark, Intarcia, Janssen Research and Development, Medicines Company, MedImmune, Merck, Novartis, Bristol-Myers Squibb, Dyrnamix. Consultant/Advisory Board; Significant; Amgen, Esperion. M.L. O’Donoghue: Research Grant; Significant; GlaxoSmithKline, Eisai, Merck&Co, Janssen, Amgen, The Medicines Company, Astra Zeneca. Total Q1 Q2 Q3 Q4 P-trend Age (Mean) 64 63 64 64 64 0.081 Female Sex 36% 34% 32% 35% 43% 0.002 eGFR (Mean) 75 75 75 76 76 0.45 Diabetes 33% 42% 33% 30% 28% <0.001 Prior HF 24% 17% 20% 24% 35% <0.001 hsCRP (Mean) 13.8 13.5 15.7 13.6 12.4 0.16 Index dx (NSTEMI) 50% 54% 53% 50% 43% <0.001 ▪ Plasma omega-6 fatty acids (Ω6-PUFA) content has been inconsistently shown to be inversely correlated with the risk of CV events in primary prevention populations. Low dietary intake of gamma-linolenic acid (GLA) has been correlated with a variety of inflammatory diseases which may contribute to the pathogenesis of atherosclerosis. ▪ We examined the relationship between Ω6-PUFA and the risk of cardiovascular events in patients with NSTE-ACS. ▪ Nested biomarker study in MERLIN-TIMI 36, a randomized controlled trial that compared ranolazine with placebo in patients with NSTE-ACS. ▪ Baseline plasma Ω6-PUFAs (7 species) was assessed through thin liquid chromatography in an cohort based case-control population. ▪ 795 cases (203 CV death, 325 MI, 271 VT, 161 AF) ▪ 1612 event-free controls ▪ Logistic regression models including a weighted likelihood approach adjusted for age, sex, BMI, hypertension, prior MI, prior HF, diabetes mellitus, smoking, eGFR, LDL-C, HDL-C, TG, statin use, index diagnosis, and treatment arm. Table 1: Baseline characteristics by Ω6-PUFA Quartiles Figure 1: Relative Proportion of Ω6-PUFA content. CONCLUSION Linoleic Acid Gamma-linolenic Acid (1.1%) Eicosadienoic Acid (0.7%) Dihomo-gammalinolenic Acid Arachidonic Acid Aolrenic Acid(0.6%) Ω6-PUFAs Other FA Figure 4: Cubic Splines. Estimated probability for CV death events in relation to GLA levels. Adjusted Adj. OR per 1 SD GLA 10 th percentile 50 th percentile 90 th percentile Unadj. OR per 1 SD
Transcript of Plasma Omega-6 Fatty Acids and the Risk of Cardiovascular ...
Figure 3: Adjusted OR per 1-SD increase of GLA. GLA remained significantly associated with a 16%
reduced odds for CV death after multivariable adjustment.
• Plasma gamma-linoleic acid content shows a significant association with the odds of CV death after ACS.
• Other Ω6-PUFAs were not consistently associated with cardiovascular events.
• Future research should examine whether dietary intake of GLA after ACS may help to attenuate CV risk.
Figure 2: Unadjusted OR per 1-SD increase.GLA was significantly associated with a 28% reduced odds for CV death after
Bonferroni-Holm correction (PB-H<0.001).
Table 2: Spearman correlations (*P<0.01)
LDL-C HDL-C TG hsCRP
Ω6-PUFA 0.14* 0.18 -0.36* -0.05*
GLA 0.06* 0.01 0.12* -0.14*
Plasma Omega-6 Fatty Acids and the Risk of Cardiovascular Events in
Patients after an Acute Coronary Syndrome: Insights from MERLIN-TIMI 36Thomas A. Zelniker1, MD, MSc; David A. Morrow1, MD, MPH; Dariush Mozaffarian2, MD, DrPH; Jianping Guo1, MSc; Kyungah Im1, PhD;
Marc S. Sabatine1, MD, MPH; Michelle O’Donoghue1, MD, MPH1 TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School 2 Friedman School of Nutrition Science and Policy, Tufts University
BACKGROUND RESULTS
METHODS
Disclosures: T.A. Zelniker: Research Grant; Significant; Deutsche Forschungsgemeinschaft (DFG ZE 1109/1-1). D.A. Morrow:
Research Grant; Significant; Abbott Labs, Amgen, Astra Zeneca, BRAHMS, Eisai, GSK, Medicines Co, Merck, Novartis, Pfizer,
Roche, Takeda. Consultant/Advisory Board; Modest; Abbott Labs, Astra Zeneca, InCardia, Peloton, Roche, Verseon.
Consultant/Advisory Board; Significant; Aralez, Bayer. D. Mozaffarian: Research Grant; Significant; National Institute of Health
and Gates Foundation. Honoraria; Significant; Acasti Pharma, GOED, DSM, Nutrition Impact, Pollock Communications, Bunge,
Indigo Agriculture, Amarin. Consultant/Advisory Board; Significant; OMmada Health, Elysium Health, DayTwo. Other; Significant;
Uptodate. J. Guo: None. K. Im: None. M.S. Sabatine: Research Grant; Significant; Amgen, AstraZeneca, Daiichi-Sankyo, Eisai,
GlaxoSmithKline, Intarcia, Janssen Research and Development, Medicines Company, MedImmune, Merck, Novartis, Pfizer,
Poxel, Takeda. Consultant/Advisory Board; Modest; AstraZeneca, CVS Caremark, Intarcia, Janssen Research and
Development, Medicines Company, MedImmune, Merck, Novartis, Bristol-Myers Squibb, Dyrnamix. Consultant/Advisory Board;
Significant; Amgen, Esperion. M.L. O’Donoghue: Research Grant; Significant; GlaxoSmithKline, Eisai, Merck&Co, Janssen,
Amgen, The Medicines Company, Astra Zeneca.
Total Q1 Q2 Q3 Q4 P-trend
Age (Mean) 64 63 64 64 64 0.081
Female Sex 36% 34% 32% 35% 43% 0.002
eGFR (Mean) 75 75 75 76 76 0.45
Diabetes 33% 42% 33% 30% 28% <0.001
Prior HF 24% 17% 20% 24% 35% <0.001
hsCRP (Mean) 13.8 13.5 15.7 13.6 12.4 0.16
Index dx (NSTEMI) 50% 54% 53% 50% 43% <0.001
▪ Plasma omega-6 fatty acids (Ω6-PUFA) content has been inconsistently shown to be inversely correlated with the risk of CV events in primary prevention populations. Low dietary intake of gamma-linolenic acid (GLA) has been correlated with a variety of inflammatory diseases which may contribute to the pathogenesis of atherosclerosis.
▪ We examined the relationship between Ω6-PUFA and the risk of cardiovascular events in patients with NSTE-ACS.
▪ Nested biomarker study in MERLIN-TIMI 36, a randomized controlled trial that compared ranolazine with placebo in patients with NSTE-ACS.
▪ Baseline plasma Ω6-PUFAs (7 species) was assessed through thin liquid chromatography in an cohort based case-control population.
▪ 795 cases (203 CV death, 325 MI, 271 VT, 161 AF)▪ 1612 event-free controls
▪ Logistic regression models including a weighted likelihood approach adjusted for age, sex, BMI, hypertension, prior MI, prior HF, diabetes mellitus, smoking, eGFR, LDL-C, HDL-C, TG, statin use, index diagnosis, and treatment arm.
Table 1: Baseline characteristics by Ω6-PUFA Quartiles
Figure 1: Relative Proportion of Ω6-PUFA content.
CONCLUSION
Linoleic Acid
Gamma-linolenic Acid (1.1%)
Eicosadienoic Acid (0.7%)
Dihomo-gammalinolenic
Acid
Arachidonic Acid
Aolrenic Acid(0.6%)
Ω6-
PU
FAs
Oth
er F
A
Figure 4: Cubic Splines. Estimated probability for
CV death events in relation to GLA levels.
Adjusted
Adj. OR per 1 SD
GLA
10th percentile 50th percentile 90th percentile
Unadj. OR per 1 SD
