Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review

doi:10.1136/bmjopen-2015-010401

Review

. 2016 Jun 12;6(6):e010401.

doi: 10.1136/bmjopen-2015-010401.

Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review

Uffe Ravnskov¹, David M Diamond², Rokura Hama³, Tomohito Hamazaki⁴, Björn Hammarskjöld⁵, Niamh Hynes⁶, Malcolm Kendrick⁷, Peter H Langsjoen⁸, Aseem Malhotra⁹, Luca Mascitelli¹⁰, Kilmer S McCully¹¹, Yoichi Ogushi¹², Harumi Okuyama¹³, Paul J Rosch¹⁴, Tore Schersten¹⁵, Sherif Sultan⁶, Ralf Sundberg¹⁶

Affiliations

¹ Magle Stora Kyrkogata 9, 22350 Lund, Sweden.
² Department of Psychology, Department of Molecular Pharmacology and Physiology, Center for Preclinical and Clinical Research on PTSD, University of South Florida, Tampa, Florida, USA.
³ NPO Japan Institute of Pharmacovigilance, Osaka, Japan.
⁴ Department of Internal Medicine, Toyama Jonan Onsen Daini Hospital, University of Toyama, Toyama City, Japan.
⁵ Strömstad Academy, Strömstad, Sweden.
⁶ Western Vascular Institute, University Hospital Galway & Galway Clinic, National University of Ireland & Royal college of Surgeons of Ireland affiliated Hospital, Galway, Ireland.
⁷ East Cheshire Trust, Macclesfield District General Hospital, Macclesfield, Cheshire, England.
⁸ Solo Practice in Cardiology, Tyler, Texas 75701, USA.
⁹ Department of cardiology, Frimley Park Hospital, Portsmouth road, Surrey GU16 7UJ, UK.
¹⁰ Medical Service, Comando Brigata Alpina "Julia"/Multinational Land Force, Udine, Italy.
¹¹ Pathology and Laboratory Medicine Service, VA Boston Healthcare System, West Roxbury; Harvard Medical School, Boston, Massachusetts.
¹² Tokai University, Daikancho, Hiratsuka, Kanagawa, Japan 254-0807.
¹³ Nagoya City University and Institute for Consumer Science and Human Life, Kinjo Gakuin University, Nagoya, Japan.
¹⁴ New York Medical College; The American Institute of Stress.
¹⁵ Sahlgren's Academy, University of Gothenburg, Sweden, and Colombia University, NY, USA.
¹⁶ Slottsstadens Läkarhus, Malmö, Gothenburg, Sweden.

PMID: 27292972
PMCID: PMC4908872
DOI: 10.1136/bmjopen-2015-010401

Review

Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review

Uffe Ravnskov et al. BMJ Open. 2016.

. 2016 Jun 12;6(6):e010401.

doi: 10.1136/bmjopen-2015-010401.

Authors

Affiliations

¹ Magle Stora Kyrkogata 9, 22350 Lund, Sweden.
² Department of Psychology, Department of Molecular Pharmacology and Physiology, Center for Preclinical and Clinical Research on PTSD, University of South Florida, Tampa, Florida, USA.
³ NPO Japan Institute of Pharmacovigilance, Osaka, Japan.
⁴ Department of Internal Medicine, Toyama Jonan Onsen Daini Hospital, University of Toyama, Toyama City, Japan.
⁵ Strömstad Academy, Strömstad, Sweden.
⁶ Western Vascular Institute, University Hospital Galway & Galway Clinic, National University of Ireland & Royal college of Surgeons of Ireland affiliated Hospital, Galway, Ireland.
⁷ East Cheshire Trust, Macclesfield District General Hospital, Macclesfield, Cheshire, England.
⁸ Solo Practice in Cardiology, Tyler, Texas 75701, USA.
⁹ Department of cardiology, Frimley Park Hospital, Portsmouth road, Surrey GU16 7UJ, UK.
¹⁰ Medical Service, Comando Brigata Alpina "Julia"/Multinational Land Force, Udine, Italy.
¹¹ Pathology and Laboratory Medicine Service, VA Boston Healthcare System, West Roxbury; Harvard Medical School, Boston, Massachusetts.
¹² Tokai University, Daikancho, Hiratsuka, Kanagawa, Japan 254-0807.
¹³ Nagoya City University and Institute for Consumer Science and Human Life, Kinjo Gakuin University, Nagoya, Japan.
¹⁴ New York Medical College; The American Institute of Stress.
¹⁵ Sahlgren's Academy, University of Gothenburg, Sweden, and Colombia University, NY, USA.
¹⁶ Slottsstadens Läkarhus, Malmö, Gothenburg, Sweden.

PMID: 27292972
PMCID: PMC4908872
DOI: 10.1136/bmjopen-2015-010401

Abstract

Objective: It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue.

Setting, participants and outcome measures: We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population.

Results: We identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found.

Conclusions: High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

Keywords: EPIDEMIOLOGY; GERIATRIC MEDICINE; PREVENTIVE MEDICINE; Risk factor, LDL-cholesterol, cardiovascular mortality, total mortality, elderly,.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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Figures

**Figure 1**
Flow Chart. CV, cardiovascular; LDL-C, low-density lipoprotein cholesterol.

See this image and copyright information in PMC

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References

1. Ravnskov U. Is atherosclerosis caused by high cholesterol? QJM 2002;95:397–403. 10.1093/qjmed/95.6.397 - DOI - PubMed
1. Hamazaki T, Okuyama H, Ogushi Y et al. . Towards a paradigm shift in cholesterol treatment—a re-examination of the cholesterol issue in Japan. Ann Nutr Metab 2015;66(Suppl 4):1–116. 10.1159/000381654 - DOI - PubMed
1. Prospective Studies Collaboration Lewington S, Whitlock G, Clarke R et al. . Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 2007;370:1829–39. 10.1016/S0140-6736(07)61778-4 - DOI - PubMed
1. Goldstein JL, Brown MS. A century of cholesterol and coronaries: from plaques to genes to statins. Cell 2015;161:161–72. 10.1016/j.cell.2015.01.036 - DOI - PMC - PubMed
1. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603–5. 10.1007/s10654-010-9491-z - DOI - PubMed

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[1] Ravnskov U. Is atherosclerosis caused by high cholesterol? QJM 2002;95:397–403. 10.1093/qjmed/95.6.397 - DOI - PubMed

[2] Ravnskov U. Is atherosclerosis caused by high cholesterol? QJM 2002;95:397–403. 10.1093/qjmed/95.6.397 - DOI - PubMed

[3] Hamazaki T, Okuyama H, Ogushi Y et al. . Towards a paradigm shift in cholesterol treatment—a re-examination of the cholesterol issue in Japan. Ann Nutr Metab 2015;66(Suppl 4):1–116. 10.1159/000381654 - DOI - PubMed

[4] Hamazaki T, Okuyama H, Ogushi Y et al. . Towards a paradigm shift in cholesterol treatment—a re-examination of the cholesterol issue in Japan. Ann Nutr Metab 2015;66(Suppl 4):1–116. 10.1159/000381654 - DOI - PubMed

[5] Prospective Studies Collaboration Lewington S, Whitlock G, Clarke R et al. . Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 2007;370:1829–39. 10.1016/S0140-6736(07)61778-4 - DOI - PubMed

[6] Prospective Studies Collaboration Lewington S, Whitlock G, Clarke R et al. . Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 2007;370:1829–39. 10.1016/S0140-6736(07)61778-4 - DOI - PubMed

[7] Goldstein JL, Brown MS. A century of cholesterol and coronaries: from plaques to genes to statins. Cell 2015;161:161–72. 10.1016/j.cell.2015.01.036 - DOI - PMC - PubMed

[8] Goldstein JL, Brown MS. A century of cholesterol and coronaries: from plaques to genes to statins. Cell 2015;161:161–72. 10.1016/j.cell.2015.01.036 - DOI - PMC - PubMed

[9] Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603–5. 10.1007/s10654-010-9491-z - DOI - PubMed

[10] Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603–5. 10.1007/s10654-010-9491-z - DOI - PubMed

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Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review

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Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review

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