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Adverse lipid profile elevates risk for subarachnoid hemorrhage: A prospective population-based cohort study

      Abstract

      Background and aims

      Studies report that both high and low total cholesterol (TC) elevates SAH risk. There are few prospective studies on high-density lipoproteins (HDL-C) and low-density lipoproteins (LDL-C), and apparently none concerns apolipoproteins A and B. We aimed to clarify the association between lipid profile and SAH risk.

      Methods

      The National FINRISK study provided risk-factor data recorded at enrolment between 1972 and 2007. During 1.52 million person-years of follow-up until 2014, 543 individuals suffered from incident hospitalized SAH or outside-hospital-fatal SAH. Cox proportional hazards model was used to calculate the hazard ratios and multiple imputation predicted ApoA1, ApoB, and LDL-C values for cohorts from a time before apolipoprotein-measurement methods were available.

      Results

      One SD elevation (1.28 mmol/l) in TC elevated SAH risk in men (hazard ratio (HR) 1.15 (95% CIs 1.00–1.32)). Low HDL-C levels increased SAH risk, as each SD decrease (0.37 mmol/l) in HDL-C raised the risk in women (HR 1.29 (95% CIs 1.07–1.55)) and men (HR 1.20 (95% CIs 1.14–1.27)). Each SD increase (0.29 g/l) in ApoA1 decreased SAH risk in women (HR 0.85 (95% CIs 0.74–0.97)) and men (HR 0.88 (95% CIs 0.76–1.02)). LDL-C (SD 1.07 mmol/l) and ApoB (SD 0.28 g/l) elevated SAH risk in men with HR 1.15 (95% CIs 1.01–1.31) and HR 1.26 (95% CIs 1.10–1.44) per one SD increase. Age did not change these findings.

      Conclusions

      An adverse lipid profile seems to elevate SAH risk similar to its effect in other cardiovascular diseases, especially in men. Whether SAH incidence diminishes with increasing statin use remains to be studied.

      Keywords

      Abbreviations:

      SAH (aneurysmal subarachnoid hemorrhage), TC (total cholesterol), HDL-C (high-density lipoprotein (calculated)), LDL-C (low-density lipoprotein (calculated)), ApoA1 (apolipoprotein A1), ApoB (apolipoprotein B), TG (triglycerides), CPD (cigarettes per day), SBP (systolic blood pressure), SES (socioeconomic status), BMI (body mass index), HR (hazard ratio), CIs (confidence intervals), SD (standard deviation), PAF (population attributable fraction), MAR (missing at random assumption)
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      References

        • Knekt P.
        • Reunanen A.
        • Aho K.
        • Heliovaara M.
        • Rissanen A.
        • Aromaa A.
        • et al.
        Risk factors for subarachnoid hemorrhage in a longitudinal population study.
        J. Clin. Epidemiol. 1991; 44: 933-939
        • Korja M.
        • Silventoinen K.
        • Laatikainen T.
        • Jousilahti P.
        • Salomaa V.
        • Hernesniemi J.
        • et al.
        Risk factors and their combined effects on the incidence rate of subarachnoid hemorrhage - a population-based cohort study.
        PLoS One. 2013; 8 (e73760)
        • Sandvei M.S.
        • Lindekleiv H.
        • Romundstad P.R.
        • Muller T.B.
        • Vatten L.J.
        • Ingebrigtsen T.
        • et al.
        Risk factors for aneurysmal subarachnoid hemorrhage - BMI and serum lipids: 11-year follow-up of the HUNT and the Tromso Study in Norway.
        Acta Neurol. Scand. 2012; 125: 382-388
        • Lindbohm J.V.
        • Kaprio J.
        • Jousilahti P.
        • Salomaa V.
        • Korja M.
        Sex, smoking, and risk for subarachnoid hemorrhage.
        Stroke. 2016; 47: 1975-1981
        • Lindbohm J.V.
        • Kaprio J.
        • Korja M.
        Cholesterol as a risk factor for subarachnoid hemorrhage: a systematic review.
        PLoS One. 2016; 11 (e0152568)
        • Zhang Y.
        • Tuomilehto J.
        • Jousilahti P.
        • Wang Y.
        • Antikainen R.
        • Hu G.
        Total and high-density lipoprotein cholesterol and stroke risk.
        Stroke. 2012; 43: 1768-1774
        • Makris G.C.
        • Lavida A.
        • Nicolaides A.N.
        • Geroulakos G.
        The effect of statins on carotid plaque morphology: a LDL-associated action or one more pleiotropic effect of statins?.
        Atherosclerosis. 2010; 213: 8-20
        • Lindbohm J.V.
        • Kaprio J.
        • Jousilahti P.
        • Salomaa V.
        • Korja M.
        Risk factors of sudden death from subarachnoid hemorrhage.
        Stroke. 2017; 48: 2399-2404
        • McQueen M.J.
        • Hawken S.
        • Wang X.
        • Ounpuu S.
        • Sniderman A.
        • Probstfield J.
        • et al.
        Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study.
        Lancet. 2008; 372: 224-233
        • Mudd J.O.
        • Borlaug B.A.
        • Johnston P.V.
        • Kral B.G.
        • Rouf R.
        • Blumenthal R.S.
        • et al.
        Beyond low-density lipoprotein cholesterol: defining the role of low-density lipoprotein heterogeneity in coronary artery disease.
        J. Am. Coll. Cardiol. 2007; 50: 1735-1741
        • Raitakari O.T.
        • Makinen V.P.
        • McQueen M.J.
        • Niemi J.
        • Juonala M.
        • Jauhiainen M.
        • et al.
        Computationally estimated apolipoproteins B and A1 in predicting cardiovascular risk.
        Atherosclerosis. 2013; 226: 245-251
        • Catapano A.L.
        • Graham I.
        • De Backer G.
        • Wiklund O.
        • Chapman M.J.
        • Drexel H.
        • et al.
        2016 ESC/EAS Guidelines for the management of Dyslipidaemias.
        Eur. Heart J. 2016; 37: 2999-3058
        • Piepoli M.F.
        • Hoes A.W.
        • Agewall S.
        • Albus C.
        • Brotons C.
        • Catapano A.L.
        • et al.
        2016 european Guidelines on cardiovascular disease prevention in clinical practice: the sixth joint task force of the european society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the european association for cardiovascular prevention & rehabilitation (EACPR).
        Eur. Heart J. 2016; 37: 2315-2381
        • Borodulin K.
        • Vartiainen E.
        • Peltonen M.
        • Jousilahti P.
        • Juolevi A.
        • Laatikainen T.
        • et al.
        Forty-year trends in cardiovascular risk factors in Finland.
        Eur. J. Publ. Health. 2015; 25: 539-546
        • Vandenbroucke J.P.
        • von Elm E.
        • Altman D.G.
        • Gotzsche P.C.
        • Mulrow C.D.
        • Pocock S.J.
        • et al.
        Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration.
        Int. J. Surg. 2014; 12: 1500-1524
        • Korja M.
        • Silventoinen K.
        • Laatikainen T.
        • Jousilahti P.
        • Salomaa V.
        • Kaprio J.
        Cause-specific mortality of 1-year survivors of subarachnoid hemorrhage.
        Neurology. 2013; 80: 481-486
        • Vartiainen E.
        • Laatikainen T.
        • Peltonen M.
        • Juolevi A.
        • Mannisto S.
        • Sundvall J.
        • et al.
        Thirty-five-year trends in cardiovascular risk factors in Finland.
        Int. J. Epidemiol. 2010; 39: 504-518
        • Tolonen H.
        • Salomaa V.
        • Torppa J.
        • Sivenius J.
        • Immonen-Raiha P.
        • Lehtonen A.
        • et al.
        The validation of the Finnish hospital Discharge register and causes of death register data on stroke diagnoses.
        Eur. J. Cardiovasc. Prev. Rehabil. 2007; 14: 380-385
        • Fine J.P.G.R.
        A proportional hazards model for the subdistribution of a competing risk.
        J. Am. Stat. Assoc. 1999; : 496-509
        • Suzuki K.
        • Izumi M.
        • Sakamoto T.
        • Hayashi M.
        Blood pressure and total cholesterol level are critical risks especially for hemorrhagic stroke in Akita, Japan.
        Cerebrovasc. Dis. 2011; 31: 100-106
      1. Royston P. Sauerbrei W. Multivariable Model-building: a Pragmatic Approach to Regression Analysis Based on Fractional Polynomials for Modelling Continuous Variables. ISBN: 978-0-470-02842-1. 2008 (Chichester, UK: Wiley)
        • Greenland S.
        • Drescher K.
        Maximum likelihood estimation of the attributable fraction from logistic models.
        Biometrics. 1993; 49: 865-872
        • Sterne J.A.
        • White I.R.
        • Carlin J.B.
        • Spratt M.
        • Royston P.
        • Kenward M.G.
        • et al.
        Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls.
        BMJ. 2009; 338 (b2393)
        • Bartlett J.W.
        • Seaman S.R.
        • White I.R.
        • Carpenter J.R.
        Alzheimer's Disease Neuroimaging Initiative*. Multiple imputation of covariates by fully conditional specification: accommodating the substantive model.
        Stat. Meth. Med. Res. 2015; 24: 462-487
        • White I.R.
        • Royston P.
        • Wood A.M.
        Multiple imputation using chained equations: issues and guidance for practice.
        Stat. Med. 2011; 30: 377-399
        • Inagawa T.
        Risk factors for the formation and rupture of intracranial saccular aneurysms in Shimane, Japan.
        World Neurosurg. 2010; 73 (discussion e23): 155-164
        • Ohkuma H.
        • Tabata H.
        • Suzuki S.
        • Islam M.S.
        Risk factors for aneurysmal subarachnoid hemorrhage in Aomori, Japan.
        Stroke. 2003; 34: 96-100
        • Tokuda Y.
        • Stein G.H.
        Serum lipids as protective factors for subarachnoid hemorrhage.
        J. Clin. Neurosci. 2005; 12: 538-541
        • Vlak M.H.
        • Rinkel G.J.
        • Greebe P.
        • Greving J.P.
        • Algra A.
        Lifetime risks for aneurysmal subarachnoid haemorrhage: multivariable risk stratification.
        J. Neurol. Neurosurg. Psychiatry. 2013; 84: 619-623
        • Korja M.
        • Lehto H.
        • Juvela S.
        • Kaprio J.
        Incidence of subarachnoid hemorrhage is decreasing together with decreasing smoking rates.
        Neurology. 2016; 87: 1118-1123
        • Doran B.
        • Guo Y.
        • Xu J.
        • Weintraub H.
        • Mora S.
        • Maron D.J.
        • et al.
        Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term mortality: insight from the National Health and Nutrition Examination Survey III (NHANES-III).
        Circulation. 2014; 130: 546-553
        • Frosen J.
        • Tulamo R.
        • Heikura T.
        • Sammalkorpi S.
        • Niemela M.
        • Hernesniemi J.
        • et al.
        Lipid accumulation, lipid oxidation, and low plasma levels of acquired antibodies against oxidized lipids associate with degeneration and rupture of the intracranial aneurysm wall.
        Acta Neuropathol Commun. 2013; 1 (71–5960-1-71)
        • Jayaraman T.
        • Paget A.
        • Shin Y.S.
        • Li X.
        • Mayer J.
        • Chaudhry H.
        • et al.
        TNF-alpha-mediated inflammation in cerebral aneurysms: a potential link to growth and rupture.
        Vasc. Health Risk Manag. 2008; 4: 805-817
        • Frosen J.
        • Tulamo R.
        • Paetau A.
        • Laaksamo E.
        • Korja M.
        • Laakso A.
        • et al.
        Saccular intracranial aneurysm: pathology and mechanisms.
        Acta Neuropathol. 2012; 123: 773-786
        • Blankenberg S.
        • Zeller T.
        • Saarela O.
        • Havulinna A.S.
        • Kee F.
        • Tunstall-Pedoe H.
        • et al.
        Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project.
        Circulation. 2010; 121: 2388-2397
        • Wilsgaard T.
        • Mathiesen E.B.
        • Patwardhan A.
        • Rowe M.W.
        • Schirmer H.
        • Lochen M.L.
        • et al.
        Clinically significant novel biomarkers for prediction of first ever myocardial infarction: the Tromso Study.
        Circ Cardiovasc Genet. 2015; 8: 363-371
        • Landenhed M.
        • Engstrom G.
        • Gottsater A.
        • Caulfield M.P.
        • Hedblad B.
        • Newton-Cheh C.
        • et al.
        Risk profiles for aortic dissection and ruptured or surgically treated aneurysms: a prospective cohort study.
        J Am Heart Assoc. 2015; 4 (e001513)
        • Holme I.
        • Aastveit A.H.
        • Hammar N.
        • Jungner I.
        • Walldius G.
        Relationships between lipoprotein components and risk of ischaemic and haemorrhagic stroke in the Apolipoprotein MOrtality RISk study (AMORIS).
        J. Intern. Med. 2009; 265: 275-287
        • Korja M.
        • Thorn L.M.
        • Hagg S.
        • Putaala J.
        • Liebkind R.
        • Harjutsalo V.
        • et al.
        Subarachnoid hemorrhage in type 1 diabetes: a prospective cohort study of 4,083 patients with diabetes.
        Diabetes Care. 2013; 36: 3754-3758
        • Lindgren A.E.
        • Kurki M.I.
        • Riihinen A.
        • Koivisto T.
        • Ronkainen A.
        • Rinne J.
        • et al.
        Type 2 diabetes and risk of rupture of saccular intracranial aneurysm in eastern Finland.
        Diabetes Care. 2013; 36: 2020-2026
        • Evangelista O.
        • McLaughlin M.A.
        Review of cardiovascular risk factors in women.
        Gend. Med. 2009; 6: 17-36
        • Tan Y.Y.
        • Gast G.C.
        • van der Schouw Y.T.
        Gender differences in risk factors for coronary heart disease.
        Maturitas. 2010; 65: 149-160
        • Howard B.V.
        • Rossouw J.E.
        Estrogens and cardiovascular disease risk revisited: the Women's Health Initiative.
        Curr. Opin. Lipidol. 2013; 24: 493-499
        • Borodulin K.
        • Vartiainen E.
        • Peltonen M.
        • Jousilahti P.
        • Juolevi A.
        • Laatikainen T.
        • et al.
        Forty-year trends in cardiovascular risk factors in Finland.
        Eur. J. Publ. Health. 2015; 25: 539-546
        • Greenland S.
        • Finkle W.D.
        A critical look at methods for handling missing covariates in epidemiologic regression analyses.
        Am. J. Epidemiol. 1995; 142: 1255-1264
        • Langkamp D.L.
        • Lehman A.
        • Lemeshow S.
        Techniques for handling missing data in secondary analyses of large surveys.
        Acad Pediatr. 2010; 10: 205-210
        • Leppala J.M.
        • Virtamo J.
        • Heinonen O.P.
        Validation of stroke diagnosis in the national hospital Discharge register and the register of causes of death in Finland.
        Eur. J. Epidemiol. 1999; 15: 155-160
        • Korja M.
        • Kaprio J.
        Controversies in epidemiology of intracranial aneurysms and SAH.
        Nat. Rev. Neurol. 2016; 12: 50-55