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      Prospective study of IL-18 and risk of MI and stroke in men and women aged 60–79 years: A nested case-control study

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          Highlights

          ► IL-18 is hypothesized to destabilise atherosclerotic plaques, leading to thrombotic events. ► We prospectively studied serum IL-18 and CHD or stroke onset in older men and women. ► IL-18 was positively associated with adverse lipid and inflammatory profile. ► Results did not suggest independent associations between IL-18 and CHD or stroke risk.

          Abstract

          Aim

          IL-18 is hypothesized to destabilise atherosclerotic plaques, leading to thrombotic events and epidemiologic studies suggest that IL-18 may increase risk of CHD or CVD.

          We examined prospective associations between levels of serum IL-18 and new CHD and stroke events in older men and women from a general population.

          Methods

          A case-control study was nested within a prospective cohort of men and women aged 60–79 years recruited from general practices in 25 British towns in 1998–2000 and followed-up for 7.5 years for fatal and non-fatal MI and stroke. Baseline IL-18 was measured in stored serum samples of incident cases of MI ( n = 364) or stroke ( n = 300) and two controls per case.

          Results

          Geometric mean IL-18 levels were higher among the 364 MI cases than the 706 controls; 417.84 pg/mL (IQR 316.25, 537.44) compared to 386.90 pg/mL (IQR 296.54, 482.33), p(difference) = 0.002. IL-18 was positively associated with adverse lipid and inflammatory profiles. Men and women in the top third of baseline IL-18 levels had an age and sex-adjusted odds ratio (OR) for MI of 1.31 (95%CI 0.92, 1.85) compared with those in the lowest third; this attenuated to 1.05 (95%CI 0.72, 1.53) after additional adjustment for established vascular and inflammatory risk factors. Each doubling of IL-18 level was associated with an increased OR for MI 1.34 (95%CI 1.04, 1.72), which was attenuated on adjustment for established vascular and inflammatory risk factors; 1.09 (95%CI 0.83, 1.44).

          Geometric mean IL-18 levels did not differ between stroke cases and controls. The OR for stroke associated with the highest compared to the lowest tertile of IL-18 was 1.24 (95%CI 0.84, 1.84). Results for MI and stroke did not differ by presence of pre-existing CVD, gender or age.

          Conclusions

          Circulating IL-18 levels were strongly associated with a range of established and novel risk factors but were not independently associated with risk of MI or stroke in our study.

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          Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.

          Sarah Lewington, Robert Clarke, Nawab Qizilbash … (2003)
          The age-specific relevance of blood pressure to cause-specific mortality is best assessed by collaborative meta-analysis of individual participant data from the separate prospective studies. Information was obtained on each of one million adults with no previous vascular disease recorded at baseline in 61 prospective observational studies of blood pressure and mortality. During 12.7 million person-years at risk, there were about 56000 vascular deaths (12000 stroke, 34000 ischaemic heart disease [IHD], 10000 other vascular) and 66000 other deaths at ages 40-89 years. Meta-analyses, involving "time-dependent" correction for regression dilution, related mortality during each decade of age at death to the estimated usual blood pressure at the start of that decade. Within each decade of age at death, the proportional difference in the risk of vascular death associated with a given absolute difference in usual blood pressure is about the same down to at least 115 mm Hg usual systolic blood pressure (SBP) and 75 mm Hg usual diastolic blood pressure (DBP), below which there is little evidence. At ages 40-69 years, each difference of 20 mm Hg usual SBP (or, approximately equivalently, 10 mm Hg usual DBP) is associated with more than a twofold difference in the stroke death rate, and with twofold differences in the death rates from IHD and from other vascular causes. All of these proportional differences in vascular mortality are about half as extreme at ages 80-89 years as at ages 40-49 years, but the annual absolute differences in risk are greater in old age. The age-specific associations are similar for men and women, and for cerebral haemorrhage and cerebral ischaemia. For predicting vascular mortality from a single blood pressure measurement, the average of SBP and DBP is slightly more informative than either alone, and pulse pressure is much less informative. Throughout middle and old age, usual blood pressure is strongly and directly related to vascular (and overall) mortality, without any evidence of a threshold down to at least 115/75 mm Hg.
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            Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies

            George Davey Smith (2003)
            Article 0 comments Cited 406 times – based on 0 reviews     Review now
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              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.

              Sarah Lewington, Gary Whitlock, Robert Clarke … (2007)
              Age, sex, and blood pressure could modify the associations of total cholesterol (and its main two fractions, HDL and LDL cholesterol) with vascular mortality. This meta-analysis combined prospective studies of vascular mortality that recorded both blood pressure and total cholesterol at baseline, to determine the joint relevance of these two risk factors. Information was obtained from 61 prospective observational studies, mostly in western Europe or North America, consisting of almost 900,000 adults without previous disease and with baseline measurements of total cholesterol and blood pressure. During nearly 12 million person years at risk between the ages of 40 and 89 years, there were more than 55,000 vascular deaths (34,000 ischaemic heart disease [IHD], 12,000 stroke, 10,000 other). Information about HDL cholesterol was available for 150,000 participants, among whom there were 5000 vascular deaths (3000 IHD, 1000 stroke, 1000 other). Reported associations are with usual cholesterol levels (ie, corrected for the regression dilution bias). 1 mmol/L lower total cholesterol was associated with about a half (hazard ratio 0.44 [95% CI 0.42-0.48]), a third (0.66 [0.65-0.68]), and a sixth (0.83 [0.81-0.85]) lower IHD mortality in both sexes at ages 40-49, 50-69, and 70-89 years, respectively, throughout the main range of cholesterol in most developed countries, with no apparent threshold. The proportional risk reduction decreased with increasing blood pressure, since the absolute effects of cholesterol and blood pressure were approximately additive. Of various simple indices involving HDL cholesterol, the ratio total/HDL cholesterol was the strongest predictor of IHD mortality (40% more informative than non-HDL cholesterol and more than twice as informative as total cholesterol). Total cholesterol was weakly positively related to ischaemic and total stroke mortality in early middle age (40-59 years), but this finding could be largely or wholly accounted for by the association of cholesterol with blood pressure. Moreover, a positive relation was seen only in middle age and only in those with below-average blood pressure; at older ages (70-89 years) and, particularly, for those with systolic blood pressure over about 145 mm Hg, total cholesterol was negatively related to haemorrhagic and total stroke mortality. The results for other vascular mortality were intermediate between those for IHD and stroke. Total cholesterol was positively associated with IHD mortality in both middle and old age and at all blood pressure levels. The absence of an independent positive association of cholesterol with stroke mortality, especially at older ages or higher blood pressures, is unexplained, and invites further research. Nevertheless, there is conclusive evidence from randomised trials that statins substantially reduce not only coronary event rates but also total stroke rates in patients with a wide range of ages and blood pressures.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cytokine
                Journal ID (iso-abbrev): Cytokine
                Title: Cytokine
                Publisher: Academic Press
                ISSN (Print): 1043-4666
                ISSN (Electronic): 1096-0023
                Publication date PMC-release: February 2013
                Publication date (Print): February 2013
                Volume: 61
                Issue: 2
                Pages: 513-520
                Affiliations
                [a ]British Regional Heart Study, UCL Dept. Primary Care & Population Health, UCL, London NW3 2PF, UK
                [b ]Division of Population Health Sciences & Education, St. George’s, University of London, Cranmer Terrace, London SW17 0RE, UK
                [c ]Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK
                [d ]Department of Non-Communicable Diseases Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
                [e ]MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK
                Author notes
                [* ]Corresponding author. Address: British Regional Heart Study, UCL Dept. Primary Care & Population Health, University College London, Rowland Hill Street, London NW3 2PF, UK. Tel.: +44 20 7794 0500x34751; fax: +44 20 7794 1224. b.jefferis@ 123456ucl.ac.uk
                Article
                Publisher ID: YCYTO52817
                DOI: 10.1016/j.cyto.2012.10.010
                PMC ID: 3561593
                PubMed ID: 23207179
                SO-VID: be75644e-a701-4eb2-807b-b192d5c49a52
                Copyright © © 2013 Elsevier Ltd.
                License:

                This document may be redistributed and reused, subject to certain conditions.

                History
                Date received : 14 May 2012
                Date revision received : 10 October 2012
                Date accepted : 12 October 2012
                Categories
                Subject: Article

                ScienceOpen disciplines: Cell biology
                Keywords: cohort,coronary heart disease,epidemiology,interleukin-18,stroke
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: cohort, coronary heart disease, epidemiology, interleukin-18, stroke

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