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      Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study

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          Abstract

          Rationale, aims and objectives

          Many clinical guidelines for cardiovascular disease (CVD) prevention contain risk estimation charts/calculators. These have shown a tendency to overestimate risk, which indicates that there might be theoretical flaws in the algorithms. Total cholesterol is a frequently used variable in the risk estimates. Some studies indicate that the predictive properties of cholesterol might not be as straightforward as widely assumed. Our aim was to document the strength and validity of total cholesterol as a risk factor for mortality in a well-defined, general Norwegian population without known CVD at baseline.

          Methods

          We assessed the association of total serum cholesterol with total mortality, as well as mortality from CVD and ischaemic heart disease (IHD), using Cox proportional hazard models. The study population comprises 52 087 Norwegians, aged 20–74, who participated in the Nord-Trøndelag Health Study (HUNT 2, 1995–1997) and were followed-up on cause-specific mortality for 10 years (510 297 person-years in total).

          Results

          Among women, cholesterol had an inverse association with all-cause mortality [hazard ratio (HR): 0.94; 95% confidence interval (CI): 0.89–0.99 per 1.0 mmol L −1 increase] as well as CVD mortality (HR: 0.97; 95% CI: 0.88–1.07). The association with IHD mortality (HR: 1.07; 95% CI: 0.92–1.24) was not linear but seemed to follow a ‘U-shaped’ curve, with the highest mortality <5.0 and ≥7.0 mmol L −1. Among men, the association of cholesterol with mortality from CVD (HR: 1.06; 95% CI: 0.98–1.15) and in total (HR: 0.98; 95% CI: 0.93–1.03) followed a ‘U-shaped’ pattern.

          Conclusion

          Our study provides an updated epidemiological indication of possible errors in the CVD risk algorithms of many clinical guidelines. If our findings are generalizable, clinical and public health recommendations regarding the ‘dangers’ of cholesterol should be revised. This is especially true for women, for whom moderately elevated cholesterol (by current standards) may prove to be not only harmless but even beneficial.

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          Most cited references97

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          2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension.

          Hypertension is estimated to cause 4.5% of current global disease burden and is as prevalent in many developing countries, as in the developed world. Blood pressure-induced cardiovascular risk rises continuously across the whole blood pressure range. Countries vary widely in capacity for management of hypertension, but worldwide the majority of diagnosed hypertensives are inadequately controlled. This statement addresses the ascertainment of overall cardiovascular risk to establish thresholds for initiation and goals of treatment, appropriate treatment strategies for non-drug and drug therapies, and cost-effectiveness of treatment. Since publication of the WHO/ISH Guidelines for the Management of Hypertension in 1999, more evidence has become available to support a systolic blood pressure threshold of 140 mmHg for even 'low-risk' patients. In high-risk patients there is evidence for lower thresholds. Lifestyle modification is recommended for all individuals. There is evidence that specific agents have benefits for patients with particular compelling indications, and that monotherapy is inadequate for the majority of patients. For patients without a compelling indication for a particular drug class, on the basis of comparative trial data, availability, and cost, a low dose of diuretic should be considered for initiation of therapy. In most places a thiazide diuretic is the cheapest option and thus most cost effective, but for compelling indications where other classes provide additional benefits, even if more expensive, they may be more cost effective. In high-risk patients who attain large benefits from treatment, expensive drugs may be cost effective, but in low-risk patients treatment may not be cost-effective unless the drugs are cheap.
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            National, regional, and global trends in systolic blood pressure since 1980: systematic analysis of health examination surveys and epidemiological studies with 786 country-years and 5·4 million participants.

            Data for trends in blood pressure are needed to understand the effects of its dietary, lifestyle, and pharmacological determinants; set intervention priorities; and evaluate national programmes. However, few worldwide analyses of trends in blood pressure have been done. We estimated worldwide trends in population mean systolic blood pressure (SBP). We estimated trends and their uncertainties in mean SBP for adults 25 years and older in 199 countries and territories. We obtained data from published and unpublished health examination surveys and epidemiological studies (786 country-years and 5·4 million participants). For each sex, we used a Bayesian hierarchical model to estimate mean SBP by age, country, and year, accounting for whether a study was nationally representative. In 2008, age-standardised mean SBP worldwide was 128·1 mm Hg (95% uncertainty interval 126·7-129·4) in men and 124·4 mm Hg (123·0-125·9) in women. Globally, between 1980 and 2008, SBP decreased by 0·8 mm Hg per decade (-0·4 to 2·2, posterior probability of being a true decline=0·90) in men and 1·0 mm Hg per decade (-0·3 to 2·3, posterior probability=0·93) in women. Female SBP decreased by 3·5 mm Hg or more per decade in western Europe and Australasia (posterior probabilities ≥0·999). Male SBP fell most in high-income North America, by 2·8 mm Hg per decade (1·3-4·5, posterior probability >0·999), followed by Australasia and western Europe where it decreased by more than 2·0 mm Hg per decade (posterior probabilities >0·98). SBP rose in Oceania, east Africa, and south and southeast Asia for both sexes, and in west Africa for women, with the increases ranging 0·8-1·6 mm Hg per decade in men (posterior probabilities 0·72-0·91) and 1·0-2·7 mm Hg per decade for women (posterior probabilities 0·75-0·98). Female SBP was highest in some east and west African countries, with means of 135 mm Hg or greater. Male SBP was highest in Baltic and east and west African countries, where mean SBP reached 138 mm Hg or more. Men and women in western Europe had the highest SBP in high-income regions. On average, global population SBP decreased slightly since 1980, but trends varied significantly across regions and countries. SBP is currently highest in low-income and middle-income countries. Effective population-based and personal interventions should be targeted towards low-income and middle-income countries. Funding Bill & Melinda Gates Foundation and WHO. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

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                Author and article information

                Journal
                J Eval Clin Pract
                jep
                Journal of Evaluation in Clinical Practice
                Blackwell Publishing Ltd (Oxford, UK )
                1356-1294
                1365-2753
                February 2012
                : 18
                : 1
                : 159-168
                Affiliations
                [1 ]simpleResearch Fellow, Research Unit of General Practice, Department of Public Health and General Practice, Norwegian University of Science and Technology (NTNU) Trondheim, Norway
                [2 ]simpleProfessor, Department of Family Medicine, University of Iceland, and Centre of Development, Primary Health Care of the Capital Area Reykjavik, Iceland
                [3 ]simpleProfessor Emeritus, Department of Primary Health Care, The Sahlgrenska Academy, University of Gothenburg Gothenburg, Sweden
                [4 ]simpleAssociate Professor, Department of Human Movement Science, Norwegian University of Science and Technology (NTNU) Trondheim, Norway
                [5 ]simpleAssociate Professor, Research Unit of General Practice, Department of Public Health and General Practice, Norwegian University of Science and Technology (NTNU) Trondheim, Norway and Landspitali University Hospital, Reykjavik, Iceland
                Author notes
                Dr Halfdan Petursson, Research Unit of General Practice, Department of Public Health and General Practice, Norwegian University of Science and Technology (NTNU), PO Box 8905, 7491 Trondheim, Norway, E-mail: halfdanpe@ 123456gmail.com

                Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms

                Article
                10.1111/j.1365-2753.2011.01767.x
                3303886
                21951982
                02432bed-4056-4a97-b17e-828e1e57533f
                © 2011 Blackwell Publishing Ltd

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : 17 August 2011
                Categories
                Commentaries

                Medicine
                mortality,cholesterol,preventive medicine,clinical guidelines,cardiovascular risk estimation,primary care

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