Features of Serum Fatty Acids at Acute Ischemic Stroke Onset in Statin-Treated Patients with Hypercholesterolemia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects and Inclusion Criteria
2.2. Measurement of Serum Lipids and FAs
2.3. Evaluation
2.4. Ethical Approval
2.5. Consent to Participate
2.6. Statistical Analysis
3. Results
4. Discussions
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Talayero, B.G.; Sacks, F.M. The role of triglycerides in atherosclerosis. Curr. Cardiol. Rep. 2011, 13, 544–552. [Google Scholar] [CrossRef] [Green Version]
- Benfante, R.; Reed, D. Is elevated serum cholesterol level a risk factor for coronary heart disease in the elderly? JAMA 1990, 263, 393–396. [Google Scholar] [CrossRef] [PubMed]
- Sasaki, J.; Arakawa, K.; Iwashita, M.; Matsushita, Y.; Kono, S. Reduction in serum total cholesterol and risks of coronary events and cerebral infarction in Japanese men: The Kyushu Lipid Intervention Study. Circ. J. 2003, 67, 473–478. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nakamura, H.; Arakawa, K.; Itakura, H.; Kitabatake, A.; Goto, Y.; Toyota, T.; Nakaya, N.; Nishimoto, S.; Muranaka, M.; Yamamoto, A.; et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): A prospective randomised controlled trial. Lancet 2006, 368, 1155–1163. [Google Scholar] [CrossRef]
- Amarenco, P.; Bogousslavsky, J.; Callahan, A.; Goldstein, L.B.; Hennerici, M.; Rudolph, A.E.; Sillesen, H.; Simunovic, L.; Szarek, M.; Welch, K.M.; et al. High-dose atorvastatin after stroke or transient ischemic attack. NEJM 2006, 355, 549–559. [Google Scholar] [CrossRef] [PubMed]
- Arnett, D.K.; Blumenthal, R.S.; Albert, M.A.; Buroker, A.B.; Goldberger, Z.D.; Hahn, E.J.; Himmelfarb, C.D.; Khera, A.; Lloyd-Jones, D.; McEvoy, J.W.; et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019, 140, e596–e646. [Google Scholar] [CrossRef] [PubMed]
- Carson, J.A.S.; Lichtenstein, A.H.; Anderson, C.A.M.; Appel, L.J.; Kris-Etherton, P.M.; Meyer, K.A.; Petersen, K.; Polonsky, T.; Van Horn, L. Dietary Cholesterol and Cardiovascular Risk: A Science Advisory From the American Heart Association. Circulation 2020, 141, e39–e53. [Google Scholar] [CrossRef] [Green Version]
- von Lossonczy, T.O.; Ruiter, A.; Bronsgeest-Schoute, H.C.; van Gent, C.M.; Hermus, R.J. The effect of a fish diet on serum lipids in healthy human subjects. Am. J. Clin. Nutr. 1978, 31, 1340–1346. [Google Scholar] [CrossRef]
- Iso, H.; Rexrode, K.M.; Stampfer, M.J.; Manson, J.E.; Colditz, G.A.; Speizer, F.E.; Hennekens, C.H.; Willett, W.C. Intake of fish and omega-3 fatty acids and risk of stroke in women. JAMA 2001, 285, 304–312. [Google Scholar] [CrossRef] [Green Version]
- Iso, H.; Kobayashi, M.; Ishihara, J.; Sasaki, S.; Okada, K.; Kita, Y.; Kokubo, Y.; Tsugane, S.; Group, J.S. Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: The Japan Public Health Center-Based (JPHC) Study Cohort I. Circulation 2006, 113, 195–202. [Google Scholar] [CrossRef] [Green Version]
- Takita, T.; Nakamura, K.; Kimira, M.; Yamada, N.; Kobayashi, Y.; Innami, S. Serum fatty acid compositions and lipid concentrations and their correlations. J. Clin. Biochem. Nutr. 1996, 20, 149–159. [Google Scholar]
- Schwertner, H.; Mosser, E. Comparison of lipid fatty acids on a concentration basis vs. weight percentage basis in patients with and without coronary artery disease or diabetes. Clin. Chem. 1993, 39, 659–663. [Google Scholar] [PubMed]
- Yokoyama, M.; Origasa, H.; Matsuzaki, M.; Matsuzawa, Y.; Saito, Y.; Ishikawa, Y.; Oikawa, S.; Sasaki, J.; Hishida, H.; Itakura, H.; et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): A randomised open-label, blinded endpoint analysis. Lancet 2007, 369, 1090–1098. [Google Scholar] [CrossRef] [PubMed]
- Tanaka, K.; Ishikawa, Y.; Yokoyama, M.; Origasa, H.; Matsuzaki, M.; Saito, Y.; Matsuzawa, Y.; Sasaki, J.; Oikawa, S.; Hishida, H.; et al. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: Subanalysis of the JELIS trial. Stroke 2008, 39, 2052–2058. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bligh, E.G.; Dyer, W.J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 1959, 37, 911–917. [Google Scholar] [CrossRef] [Green Version]
- Dyerberg, J.; Bang, H.O. A hypothesis on the development of acute myocardial infarction in Greenlanders. J. Clin. Lab. Investig. 1982, 161, 7–13. [Google Scholar]
- Kromhout, D.; Bosschieter, E.B.; Coulander, C.d.L. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N. Engl. J. Med. 1985, 312, 1205–1209. [Google Scholar] [CrossRef]
- Miyagawa, N.; Miura, K.; Okuda, N.; Kadowaki, T.; Takashima, N.; Nagasawa, S.Y.; Nakamura, Y.; Matsumura, Y.; Hozawa, A.; Fujiyoshi, A.; et al. Long-chain n-3 polyunsaturated fatty acids intake and cardiovascular disease mortality risk in Japanese: A 24-year follow-up of NIPPON DATA80. Atherosclerosis 2014, 232, 384–389. [Google Scholar] [CrossRef]
- Morise, A.; Sérougne, C.; Gripois, D.; Blouquit, M.-F.; Lutton, C.; Hermier, D. Effects of dietary alpha linolenic acid on cholesterol metabolism in male and female hamsters of the LPN strain. J. Nutr. Biochem. 2004, 15, 51–61. [Google Scholar] [CrossRef]
- Sacks, F.M.; Lichtenstein, A.H.; Wu, J.H.Y.; Appel, L.J.; Creager, M.A.; Kris-Etherton, P.M.; Miller, M.; Rimm, E.B.; Rudel, L.L.; Robinson, J.G.; et al. Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association. Circulation 2017, 136, e1–e23. [Google Scholar] [CrossRef] [PubMed]
- Abdelmagid, S.A.; Clarke, S.E.; Nielsen, D.E.; Badawi, A.; El-Sohemy, A.; Mutch, D.M.; Ma, D.W. Comprehensive profiling of plasma fatty acid concentrations in young healthy Canadian adults. PLoS ONE 2015, 10, e0116195. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Variables | Statin Group (n = 133) | Non-Treated Group (n = 55) | p |
---|---|---|---|
Age (MD, IQR) (Min, Max) years | 75 (70.5–82.5) (Min: 52, Max: 99) | 71 (61–80) (Min: 39, Max: 97) | <0.001 |
Male sex | 85(63.9%) | 21 (38.2) | 0.0012 |
Height (MD, IQR) cm | 162 (153.8–168) | 156 (150–165) | 0.06 |
Body weight (MD, IQR) kg | 60 (53–67.9) | 58 (50.6–68) | 0.27 |
Body mass index (MD, IQR) kg/m2 | 23.1 (21.1–25.4) | 22.9 (21.0–25.4) | 0.95 |
Glucose and lipids | |||
Glucose (MD, IQR) mmol/L | 6.72 (5.91–8.22) | 7.72 (6.00–9.77) | 0.051 |
Hemoglobin A1c (HbA1c) (MD, IQR) % (NGSP) | 6.0 (5.7–6.6) | 6.1 (5.7–7.6) | 0.34 |
Total cholesterol (MD, IQR) mmol/L | 4.50 (4.03–5.09) | 7.01 (6.72–7.47) | <0.001 |
High-density lipoprotein-cholesterol (HDL-C) (MD, IQR) mmol/L | 1.42 (1.19–1.72) | 1.52 (1.33–1.87) | 0.04 |
Triglycerides (MD, IQR) mmol/L | 1.21 (0.85–1.69) | 1.65 (1.22–3.06) | <0.001 |
Low-density lipoprotein-cholesterol (LDL-C) (MD, IQR) mmol/L | 2.42 (1.97–3.02) | 4.41 (4.04–5.10) | <0.001 |
ABP (MD, IQR) mmHg | 109 (99.5–117) | 125 (108–141) | <0.001 |
Antihypertensive drugs | 96 (72%) | 15 (27%) | <0.001 |
Fatty Acids | Statin Group (n = 133) | Non-Treated Group (n = 55) | p |
---|---|---|---|
Saturated fatty acids | |||
Lauric acid (LaA) (MD, IQR) μmol/L | 4.49 (2.99–7.98) | 4.49 (2.99–10.48) | 0.66 |
Myristic acid (MyA) (MD, IQR) μmol/L | 64.39 (50.59–93.08) | 91.54 (65.26–122.2) | <0.001 |
Palmitic acid (PA) (MD, IQR) μmol/L | 2337 (1993–2825) | 3046 (2771–3694) | <0.001 |
Stearic acid (StA) (MD, IQR) μmol/L | 612.8 (531.9–714.9) | 781.4 (682.2–886.0) | <0.001 |
LaA (MD, IQR) wt % | 0 (0–0.1) | 0 (0–0.1) | 0.26 |
MyA (MD, IQR) wt % | 0.6 (0.5–0.7) | 0.6 (0.5–0.8) | 0.58 |
PA (MD, IQR) wt % | 23.4 (22.5–24.4) | 23.6 (22.7–24.9) | 0.31 |
StA (MD, IQR) wt % | 6.8 (6.2–7.3) | 6.6 (5.9–7) | 0.02 |
n-9 MUFA | |||
Oleic acid (OlA) (MD, IQR) μmol/L | 1950 (1576–2474) | 2555 (2180–3110) | <0.001 |
OlA (MD, IQR) wt % | 21.5 (19.8–23.7) | 21.4 (19.6–23.7) | 0.64 |
n-6 PUFAs | |||
Linoleic acid (LiA) (MD, IQR) μmol/L | 2312 (2011–2659) | 3126 (2824–3667) | <0.001 |
Dihomo-gamma-linolenic acid (DGLA) (MD, IQR) μmol/L | 87.69 (69.60–110.35) | 125.18 (88.02–157.46) | <0.001 |
Arachidonic acid (AA) (MD, IQR) μmol/L | 536.0 (454.1–603.5) | 674.7 (599.9–805.9) | <0.001 |
LiA (MD, IQR) wt % | 25.3 (22.6–26.7) | 26.3 (23.4–28.5) | 0.03 |
DGLA (MD, IQR) wt % | 1 (0.9–1.2) | 1.1 (0.9–1.2) | 0.54 |
AA (MD, IQR) wt % | 6.3 (5.5–7.3) | 6.1 (5.3–6.8) | 0.21 |
n-3 PUFAs | |||
Alpha-linolenic acid (AlA) (MD, IQR) μmol/L | 56.0 (42.0–82.0) | 84.37 (65.34–100.88) | <0.001 |
Eicosapentaenoic acid (EPA) (MD, IQR) μmol/L | 182.7 (142.2–305.0) | 261.5 (152.9–344.2) | 0.20 |
Docosahexaenoic acid (DHA) (MD, IQR) μmol/L | 355.98 (294.88–441.86) | 468.46 (386.1–572.1) | <0.001 |
AlA (MD, IQR) wt % | 0.6 (0.5–0.8) | 0.7 (0.6–0.8) | 0.18 |
EPA (MD, IQR) wt % | 2.2 (1.7–3.5) | 2.1 (1.1–3.2) | 0.09 |
DHA (MD, IQR) wt % | 4.5 (3.9–5.4) | 4.4 (3.6–5.6) | 0.65 |
EPA/AA ratio (MD, IQR) | 0.34 (0.26–0.58) | 0.33 (0.2–0.51) | 0.15 |
n-6/n-3 ratio (MD, IQR) | 4.12 (3.14–5.14) | 4.54 (3.09–6.06) | 0.13 |
Variables | N | Odds Ratio (95% CI) | p | AUC |
---|---|---|---|---|
Total cholesterol ≤5.66 mmol/L | 188 | 0.936 | ||
group (1: statin, 0: no statin) | 4.82 × 1010 (0–∞) | <0.001 | ||
ABP | 0.98 (0.95–0.1.01) | 0.15 | ||
Sex (1: male, 0: female) | 4.21 (1.40–12.67) | 0.009 | ||
age | 1.05 (0.99–1.11) | 0.13 | ||
Low-density lipoprotein-cholesterol ≤3.6 mmol/L | 188 | 0.911 | ||
group (1: statin, 0: no statin) | 103.1 (31.1–451.3) | <0.001 | ||
ABP | 1.00 (0.97–1.03) | 0.85 | ||
Sex (1: male, 0: female) | 5.88 (2.08–19.39) | 0.001 | ||
age | 0.99 (0.94–1.06) | 0.98 | ||
Triglycerides ≤1.69 mmol/L | 188 | 0.694 | ||
group (1: statin, 0: no statin) | 1.45 (0.67–3.12) | 0.35 | ||
ABP | 0.97 (0.95–0.99) | 0.003 | ||
Sex (1: male, 0: female) | 0.95 (0.47–1.91) | 0.89 | ||
age | 1.03 (0.99–1.68) | 0.06 | ||
High-density lipoprotein-cholesterol ≤1.74 mmol/L | 188 | 0.663 | ||
group (1: statin, 0: no statin) | 2.43(1.10–5.35) | 0.03 | ||
ABP | 1.01 (0.99–1.03) | 0.47 | ||
Sex (1: male, 0: female) | 1.91 (0.95–3.84) | 0.07 | ||
age | 0.98 (0.94–1.01) | 0.19 |
N | Odds Ratio (95% CI) | p | AUC | |
---|---|---|---|---|
Myristic acid ≤65.3 μmol/L | 188 | 0.652 | ||
group (1: statin, 0: no statin) | 2.53 (1.17–5.45) | 0.02 | ||
ABP | 0.98 (0.97–1.00) | 0.07 | ||
Sex (1: male, 0: female) | 0.99 (0.53–1.88) | 0.99 | ||
age | 1.00 (0.97–1.03) | 0.96 | ||
Palmitic acid ≤2771 μmol/L | 188 | 0.797 | ||
group (1: statin, 0: no statin) | 6.80 (2.92–15.80) | <0.001 | ||
ABP | 0.96 (0.94–0.98) | <0.001 | ||
Sex (1: male, 0: female) | 0.50 (0.23–1.07) | 0.07 | ||
age | 1.01 (0.98–1.05) | 0.47 | ||
Stearic acid ≤682.2 μmol/L | 188 | 0.773 | ||
group (1: statin, 0: no statin) | 4.29 (1.96–9.43) | <0.001 | ||
ABP | 0.97 (0.95–0.99) | 0.001 | ||
Sex (1: male, 0: female) | 0.80 (0.40–1.62) | 0.54 | ||
age | 1.02 (0.99–1.06) | 0.16 | ||
Oleic acid ≤2180 μmol/L | 188 | 0.777 | ||
group (1: statin, 0: no statin) | 4.34 (1.91–9.84) | <0.001 | ||
ABP | 0.97 (0.95–0.99) | <0.001 | ||
Sex (1: male, 0: female) | 0.51 (0.25–1.04) | 0.06 | ||
age | 1.03 (0.99–1.06) | 0.11 |
N | Odds Ratio (95% CI) | p | AUC | |
---|---|---|---|---|
Linoleic acid (LiA) ≤2824 μmol/L | 188 | 0.832 | ||
group (1: statin, 0: no statin) | 8.81 (3.88–20.01) | <0.001 | ||
ABP | 0.97 (0.95–0.99) | 0.010 | ||
Sex (1: male, 0: female) | 1.16 (0.52–2.59) | 0.71 | ||
Age | 1.05 (1.01–1.10) | 0.009 | ||
Dihomo-gamma-linolenic acid ≤88.0 μmol/L | 188 | 0.716 | ||
group (1: statin, 0: no statin) | 2.01 (0.91–4.45) | 0.08 | ||
ABP | 0.97 (0.95–0.99) | <0.001 | ||
Sex (1: male, 0: female) | 0.88 (0.45–1.70) | 0.70 | ||
Age | 1.03 (0.99–1.06) | 0.14 | ||
Arachidonic acid ≤599.9 μmol/L | 188 | 0.790 | ||
group (1: statin, 0: no statin) | 6.27 (2.84–13.85) | <0.001 | ||
ABP | 0.99 (0.98–1.01) | 0.57 | ||
Sex (1: male, 0: female) | 1.73 (0.85–3.49) | 0.13 | ||
age | 1.04 (1.01–1.08) | 0.02 | ||
Alpha-linolenic acid ≤65.3 μmol/L | 188 | 0.729 | ||
group (1: statin, 0: no statin) | 3.34 (1.53–7.32) | 0.002 | ||
ABP | 0.97 (0.95–0.99) | 0.003 | ||
Sex (1: male, 0: female) | 1.12 (0.58–2.16) | 0.73 | ||
age | 1.01 (0.97–1.04) | 0.74 | ||
Docosahexaenoic acid ≤386.1 μmol/L | 188 | 0.699 | ||
group (1: statin, 0: no statin) | 3.88 (1.79–8.42) | <0.001 | ||
ABP | 0.98 (0.96–0.99) | 0.04 | ||
Sex (1: male, 0: female) | 1.18 (0.62–2.26) | 0.61 | ||
age | 0.99 (0.96–1.02) | 0.58 | ||
Stearic acid wt % ≤5.9% | 188 | 0.613 | ||
group (1: statin, 0: no statin) | 0.39 (0.16–0.97) | 0.04 | ||
ABP | 1.00 (0.98–1.02) | 0.99 | ||
Sex (1: male, 0: female) | 1.10 (0.49–2.48) | 0.82 | ||
Age | 1.02 (0.98–1.06) | 0.29 | ||
LiA wt % ≤23.4% | 188 | 0.603 | ||
group (1: statin, 0: no statin) | 2.04 (0.90–4.61) | 0.08 | ||
ABP | 1.02 (1.00–1.04) | 0.04 | ||
Sex (1: male, 0: female) | 0.86 (0.44–1.69) | 0.68 | ||
Age | 0.99 (0.96–1.08) | 0.73 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Mori, T.; Yoshioka, K.; Tanno, Y.; Kasakura, S. Features of Serum Fatty Acids at Acute Ischemic Stroke Onset in Statin-Treated Patients with Hypercholesterolemia. Nutrients 2020, 12, 2833. https://doi.org/10.3390/nu12092833
Mori T, Yoshioka K, Tanno Y, Kasakura S. Features of Serum Fatty Acids at Acute Ischemic Stroke Onset in Statin-Treated Patients with Hypercholesterolemia. Nutrients. 2020; 12(9):2833. https://doi.org/10.3390/nu12092833
Chicago/Turabian StyleMori, Takahisa, Kazuhiro Yoshioka, Yuhei Tanno, and Shigen Kasakura. 2020. "Features of Serum Fatty Acids at Acute Ischemic Stroke Onset in Statin-Treated Patients with Hypercholesterolemia" Nutrients 12, no. 9: 2833. https://doi.org/10.3390/nu12092833
APA StyleMori, T., Yoshioka, K., Tanno, Y., & Kasakura, S. (2020). Features of Serum Fatty Acids at Acute Ischemic Stroke Onset in Statin-Treated Patients with Hypercholesterolemia. Nutrients, 12(9), 2833. https://doi.org/10.3390/nu12092833