Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2024

Open Access 01-12-2024 | Stroke | Research

The association between inflammation, arterial stiffness, oxidized LDL and cardiovascular disease in Finnish men with metabolic syndrome – a 15-year follow-up study

Authors: Harri Juhani Saarinen, Jorma Lahtela, Päivi Mähönen, Ari Palomäki, for the Hämeenlinna Metabolic Syndrome Research Program Study Group

Published in: BMC Cardiovascular Disorders | Issue 1/2024

Login to get access

Abstract

Background

All-cause mortality and cardiovascular disease are increased in subjects with metabolic syndrome (MetS). Risk scores are used to predict individual risk of heart disease. We performed a long-term follow-up study to investigate whether risk scores and cardiovascular risk factors such as arterial stiffness, high-sensitive C-reactive protein (hs-CRP) and oxidized LDL (OxLDL) can be used to predict cardiovascular events in Finnish men with MetS.

Methods

After baseline measurements we followed 105 Finnish men aged 30 to 65 years with MetS for a mean period of 16.4 years. The primary outcome of the study was a composite of myocardial infarction, stroke, symptomatic vascular disease diagnosed with invasive angiography, coronary or peripheral revascularization, amputation due to peripheral vascular disease, cardiovascular death and non-cardiovascular death. The endpoints were retrieved from electronic medical records.

Results

The number of acute myocardial infarctions and strokes during the first 10 years was lower than estimated by FINRISK score but SCORE predicted cardiovascular death correctly. During the whole follow-up period, 27 of 105 participants (25.8%) had 30 endpoint events. The incidence of the primary composite outcome was significantly lower in subjects with hs-CRP < 1.0 mg/L than in subjects with hs-CRP ≥ 1.0 mg/L (6 of 41 subjects [14.6%] vs. 21 of 64 subjects [32.8%]; p = 0.036). The incidence of the primary composite outcome was higher among subjects with large artery elasticity classified as borderline compared to subjects with normal large artery elasticity (5 of 10 subjects [50%] vs. 22 of 93 subjects [24%]; p = 0.05). There was no difference in the incidence of primary composite outcome in groups with different degrees of small artery elasticity or different level of oxLDL.

Conclusions

Men with MetS who had hs-CRP ≥ 1.0 mg/L had higher risk for CVD and all-cause mortality than those with hs-CRP of < 1.0 mg/L. This also applies to subjects with borderline decreased large artery elasticity. The amount of OxLDL had no predictive value on the incidence of CVD and all-cause mortality. Men with MetS participating in the Hämeenlinna Metabolic Syndrome Research Program without lifestyle or drug intervention had better outcome for myocardial infarction or stroke than estimated by the FINRISK score.

Trial registration

ClinicalTrials.gov NCT01119404 retrospectively registered 07/05/2010.
Literature
1.
go back to reference Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. J Am Med Assoc. 2002;288(21):2709–16.CrossRef Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. J Am Med Assoc. 2002;288(21):2709–16.CrossRef
2.
go back to reference Conroy R. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24(11):987–1003.CrossRefPubMed Conroy R. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24(11):987–1003.CrossRefPubMed
3.
go back to reference Vartiainen E, Laatikainen T, Peltonen M, Puska P. Predicting Coronary Heart Disease and Stroke: the FINRISK calculator. Glob Heart. 2016;11(2):213–6.CrossRefPubMed Vartiainen E, Laatikainen T, Peltonen M, Puska P. Predicting Coronary Heart Disease and Stroke: the FINRISK calculator. Glob Heart. 2016;11(2):213–6.CrossRefPubMed
4.
go back to reference Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of Cardiovascular Disease in apparently healthy men. N Engl J Med. 1997;336(14):973–9.CrossRefPubMed Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of Cardiovascular Disease in apparently healthy men. N Engl J Med. 1997;336(14):973–9.CrossRefPubMed
5.
go back to reference Cecelja M, Chowienczyk P. Role of arterial stiffness in cardiovascular disease. JRSM Cardiovasc Dis. 2012;1(4):1–10.CrossRef Cecelja M, Chowienczyk P. Role of arterial stiffness in cardiovascular disease. JRSM Cardiovasc Dis. 2012;1(4):1–10.CrossRef
6.
go back to reference Hopkins KD, Lehmann ED, Gosling RG. Aortic compliance measurements: a non-invasive indicator of atherosclerosis? Lancet. 1994;343(8911):1447.CrossRefPubMed Hopkins KD, Lehmann ED, Gosling RG. Aortic compliance measurements: a non-invasive indicator of atherosclerosis? Lancet. 1994;343(8911):1447.CrossRefPubMed
7.
go back to reference Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem. 1997;272(34):20963–6.CrossRefPubMed Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem. 1997;272(34):20963–6.CrossRefPubMed
8.
go back to reference Pohjantähti-Maaroos H, Palomäki A, Kankkunen P, Husgafvel S, Knuth T, Vesterinen K, et al. Arterial elasticity and oxidized LDL among men with metabolic syndrome and different 10-year cardiovascular risk estimated by FINRISK and SCORE models. Ann Med. 2012;44(5):503–12.CrossRefPubMed Pohjantähti-Maaroos H, Palomäki A, Kankkunen P, Husgafvel S, Knuth T, Vesterinen K, et al. Arterial elasticity and oxidized LDL among men with metabolic syndrome and different 10-year cardiovascular risk estimated by FINRISK and SCORE models. Ann Med. 2012;44(5):503–12.CrossRefPubMed
9.
go back to reference Expert Panel on Detection. Evaluation, and treatment of high blood cholesterol in adults E and T of HBC in A. Executive Summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA: J Am Med Association. 2001;285(19):2486–97.CrossRef Expert Panel on Detection. Evaluation, and treatment of high blood cholesterol in adults E and T of HBC in A. Executive Summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA: J Am Med Association. 2001;285(19):2486–97.CrossRef
10.
go back to reference Holvoet P, Lee DH, Steffes M, Gross M, Jacobs DR. Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome. JAMA. 2008;299(19):2287–93.CrossRefPubMedPubMedCentral Holvoet P, Lee DH, Steffes M, Gross M, Jacobs DR. Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome. JAMA. 2008;299(19):2287–93.CrossRefPubMedPubMedCentral
11.
go back to reference Ridker PM, Brown NJ, Vaughan DE, Harrison DG, Mehta JL. Established and emerging plasma biomarkers in the prediction of first atherothrombotic events. Circulation. 2004;109(25 Suppl 1):IV6–19.PubMed Ridker PM, Brown NJ, Vaughan DE, Harrison DG, Mehta JL. Established and emerging plasma biomarkers in the prediction of first atherothrombotic events. Circulation. 2004;109(25 Suppl 1):IV6–19.PubMed
12.
go back to reference Cohn JN, Finkelstein S, McVeigh G, Morgan D, LeMay L, Robinson J, et al. Noninvasive pulse wave analysis for the early detection of vascular disease. Hypertension. 1995;26(3):503–8.CrossRefPubMed Cohn JN, Finkelstein S, McVeigh G, Morgan D, LeMay L, Robinson J, et al. Noninvasive pulse wave analysis for the early detection of vascular disease. Hypertension. 1995;26(3):503–8.CrossRefPubMed
13.
go back to reference Cohn JN. Vascular wall function as a risk marker for cardiovascular disease. J Hypertens Suppl. 1999;17(5):41–4. Cohn JN. Vascular wall function as a risk marker for cardiovascular disease. J Hypertens Suppl. 1999;17(5):41–4.
14.
go back to reference Prisant LM, Pasi M, Jupin D, Prisant ME. Assessment of repeatability and correlates of arterial compliance. Blood Press Monit. 2002;7(4):231–5.CrossRefPubMed Prisant LM, Pasi M, Jupin D, Prisant ME. Assessment of repeatability and correlates of arterial compliance. Blood Press Monit. 2002;7(4):231–5.CrossRefPubMed
15.
go back to reference Zimlichman R, Shargorodsky M, Boaz M, Duprez D, Rahn KH, Rizzoni D, et al. Determination of arterial compliance using blood pressure waveform analysis with the CR-2000 system: Reliability, repeatability, and establishment of normal values for healthy European population—the seven European sites study (SESS). Am J Hypertens. 2005;18(1):65–71.CrossRefPubMed Zimlichman R, Shargorodsky M, Boaz M, Duprez D, Rahn KH, Rizzoni D, et al. Determination of arterial compliance using blood pressure waveform analysis with the CR-2000 system: Reliability, repeatability, and establishment of normal values for healthy European population—the seven European sites study (SESS). Am J Hypertens. 2005;18(1):65–71.CrossRefPubMed
16.
go back to reference Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-Reactive protein. N Engl J Med. 2008;359(21):2195–207.CrossRefPubMed Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-Reactive protein. N Engl J Med. 2008;359(21):2195–207.CrossRefPubMed
18.
go back to reference Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Anti-inflammatory therapy with Canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119–31.CrossRefPubMed Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Anti-inflammatory therapy with Canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119–31.CrossRefPubMed
20.
go back to reference Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019;381(26):2497–505.CrossRefPubMed Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019;381(26):2497–505.CrossRefPubMed
21.
go back to reference Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, et al. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020;383(19):1838–47.CrossRefPubMed Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, et al. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020;383(19):1838–47.CrossRefPubMed
22.
go back to reference Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320(14):915–24.PubMed Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320(14):915–24.PubMed
23.
go back to reference Trpkovic A, Resanovic I, Stanimirovic J, Radak D, Mousa SA, Cenic-Milosevic D, et al. Oxidized low-density lipoprotein as a biomarker of cardiovascular diseases. Crit Rev Clin Lab Sci. 2015;52(2):70–85.CrossRefPubMed Trpkovic A, Resanovic I, Stanimirovic J, Radak D, Mousa SA, Cenic-Milosevic D, et al. Oxidized low-density lipoprotein as a biomarker of cardiovascular diseases. Crit Rev Clin Lab Sci. 2015;52(2):70–85.CrossRefPubMed
24.
go back to reference Poznyak AV, Nikiforov NG, Markin AM, Kashirskikh DA, Myasoedova VA, Gerasimova EV, et al. Overview of OxLDL and its impact on Cardiovascular Health: focus on atherosclerosis. Front Pharmacol. 2021;11:613780.CrossRefPubMedPubMedCentral Poznyak AV, Nikiforov NG, Markin AM, Kashirskikh DA, Myasoedova VA, Gerasimova EV, et al. Overview of OxLDL and its impact on Cardiovascular Health: focus on atherosclerosis. Front Pharmacol. 2021;11:613780.CrossRefPubMedPubMedCentral
25.
go back to reference Kuklinska AM, Mroczko B, Musial WJ, Usowicz-Szarynska M, Sawicki R, Borowska H, et al. Diagnostic biomarkers of essential arterial hypertension: the value of prostacyclin, nitric oxide, oxidized-LDL, and peroxide measurements. Int Heart J. 2009;50(3):341–51.CrossRefPubMed Kuklinska AM, Mroczko B, Musial WJ, Usowicz-Szarynska M, Sawicki R, Borowska H, et al. Diagnostic biomarkers of essential arterial hypertension: the value of prostacyclin, nitric oxide, oxidized-LDL, and peroxide measurements. Int Heart J. 2009;50(3):341–51.CrossRefPubMed
26.
go back to reference Sigurdardottir V, Fagerberg B, Hulthe J. Circulating oxidized low-density lipoprotein (LDL) is associated with risk factors of the metabolic syndrome and LDL size in clinically healthy 58-year-old men (AIR study). J Intern Med. 2002;252(5):440–7.CrossRefPubMed Sigurdardottir V, Fagerberg B, Hulthe J. Circulating oxidized low-density lipoprotein (LDL) is associated with risk factors of the metabolic syndrome and LDL size in clinically healthy 58-year-old men (AIR study). J Intern Med. 2002;252(5):440–7.CrossRefPubMed
27.
go back to reference Lapointe A, Couillard C, Piché MÈ, Weisnagel SJ, Bergeron J, Nadeau A, et al. Circulating oxidized LDL is associated with parameters of the metabolic syndrome in postmenopausal women. Atherosclerosis. 2007;191(2):362–8.CrossRefPubMed Lapointe A, Couillard C, Piché MÈ, Weisnagel SJ, Bergeron J, Nadeau A, et al. Circulating oxidized LDL is associated with parameters of the metabolic syndrome in postmenopausal women. Atherosclerosis. 2007;191(2):362–8.CrossRefPubMed
28.
go back to reference Xu S, Ogura S, Chen J, Little PJ, Moss J, Liu P. LOX-1 in atherosclerosis: biological functions and pharmacological modifiers. Cell Mol Life Sci. 2013;70(16):2859–72.CrossRefPubMed Xu S, Ogura S, Chen J, Little PJ, Moss J, Liu P. LOX-1 in atherosclerosis: biological functions and pharmacological modifiers. Cell Mol Life Sci. 2013;70(16):2859–72.CrossRefPubMed
29.
go back to reference Maloberti A, Vallerio P, Triglione N, Occhi L, Panzeri F, Bassi I, et al. Vascular aging and disease of the large vessels: role of inflammation. High Blood Press Cardiovasc Prev. 2019;26(3):175–82.CrossRefPubMed Maloberti A, Vallerio P, Triglione N, Occhi L, Panzeri F, Bassi I, et al. Vascular aging and disease of the large vessels: role of inflammation. High Blood Press Cardiovasc Prev. 2019;26(3):175–82.CrossRefPubMed
31.
go back to reference O’Fee K, Deych E, Ciani O, Brown DL. Assessment of Nonfatal myocardial infarction as a surrogate for all-cause and Cardiovascular Mortality in Treatment or Prevention of Coronary Artery Disease: a Meta-analysis of Randomized clinical trials. JAMA Intern Med. 2021;181(12):1575–87.CrossRefPubMedPubMedCentral O’Fee K, Deych E, Ciani O, Brown DL. Assessment of Nonfatal myocardial infarction as a surrogate for all-cause and Cardiovascular Mortality in Treatment or Prevention of Coronary Artery Disease: a Meta-analysis of Randomized clinical trials. JAMA Intern Med. 2021;181(12):1575–87.CrossRefPubMedPubMedCentral
Metadata
Title
The association between inflammation, arterial stiffness, oxidized LDL and cardiovascular disease in Finnish men with metabolic syndrome – a 15-year follow-up study
Authors
Harri Juhani Saarinen
Jorma Lahtela
Päivi Mähönen
Ari Palomäki
for the Hämeenlinna Metabolic Syndrome Research Program Study Group
Publication date
01-12-2024
Publisher
BioMed Central
Keyword
Stroke
Published in
BMC Cardiovascular Disorders / Issue 1/2024
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-024-03818-x

Other articles of this Issue 1/2024

BMC Cardiovascular Disorders 1/2024 Go to the issue