Assessment of Risk Factors for Coronary Heart Disease in Vascular Medicine: Long-Term Experience and a Personal View from the Laboratory

Physicians should be properly informed of the clinical chemistry diagnostic potential for the diagnosis and classification of hyper- and dyslipidemias by laboratory determinations of lipids, lipoproteins, and apolipoproteins. New analytes are regularly found to be relevant for screening and risk estimation for coronary artery disease in vascular medicine. These analytes can be distinguished between parameters working on the long-term or working acutely. However, in times of restricted laboratory budgets, it is not always possible to add the new analyte to the routine diagnostic supply without having answered the question of whether the new analyte indeed adds to the chronic or acute risk estimation power presently available. This is relevant for homocysteine and for C-reactive protein (CRP). Both parameters appear to be interrelated to most common cardiovascular risk factors supposed to promote atherosclerosis and to ultimately provoke cardiovascular disease, and in fact are not independent. The latter certainly has added value in acute situations. With regard to the chronic risk estimators, it must be concluded that there is a multifactorial influence, with an important contribution made by social and lifestyle factors. This review draws attention to the multifactorial aspects of coronary heart disease, risk profiling using computer programs, socioeconomic factors, and implementation problems of interventions.

Multifactorial analysis - clinical management - lifestyle - homocystein - C-reactive protein - gene versus environment

REFERENCES

• 1 Fredrickson D S, Levy R I, Lees R S. Fat transport in lipoproteins.  N Engl J Med. 1967;  276 273-281
• 2 Hutchison B, Birch S, Evans C E et al.. Screening for hypercholesterolaemia in primary care: randomised controlled trial of postal questionnaire appraising risk of coronary heart disease.  BMJ. 1998;  316 1208-1212
• 3 Hingorani A D, Vallance P. A simple computer program for guiding management of cardiovascular risk factors and prescribing.  BMJ. 1999;  318 101-105
• 4 Assmann G, Cullen P, Schulte H. Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the Prospective Cardiovascular Münster (PROCAM) study.  Circulation. 2002;  105 310-315
• 5 Murdoch M, Wilt T J. Cholesterol awareness after case-finding: do patients really know their cholesterol numbers?.  Am J Prev Med. 1997;  13 284-289
• 6 Cholesterol and coronary heart disease: screening and treatment.  Effective Health Care. 1998;  4 1-15 , Editorial
• 7 Hulley S B, Grady D, Browner W S. Statins; underused by those who would benefit, but caution is needed for young people at low risk of cardiovascular disease.  BMJ. 2000;  321 971-972
• 8 Strychar Y M, Champagne F, Ghadirian P, Bonin A, Jenicek M, Lasater T HM. Impact of receiving blood cholesterol test results on dietary change.  Am J Prev Med. 1998;  14 103-110
• 9 Eerste herziening NHG-Standaard Cholesterol .Actualisering en de Consensus Cholesterol, tweede herziening april 1998. Behandeling en preventie van coronaire hartziekten door verlaging van de plasmacholesterol-concentratie. CBO Utrecht. http://www.bmas.nl/gi_rtch_.htm
• 10 Grundy S M. Low-density lipoprotein, non-high density lipoprotein and apolipoprotein B as targets of lipid-lowering therapy.  Circulation. 2002;  106 2526-2529
• 11 Miremadi S, Sniderman A, Frolich J. Can measurement of serum apolipoprotein B replace the lipid profile monitoring of patients with lipoprotein disorders?.  Clin Chem. 2002;  48 484-488
• 12 Talmud P J, Hawe E, Miller G J, Humphries S E. Non-fasting apolipoprotein B and triglyceride levels as a useful predictor of coronary heart disease risk in middle-aged UK men.  Arterioscler Thromb Vasc Biol. 2002;  22 1918-1923
• 13 Wiegman A, Rodenburg J, de Jongh S et al.. Family history and cardiovascular risk in familial hypercholesterolemia. Data in more than 1000 children.  Circulation. 2003;  25 1473-1478
• 14 Naghavi M, Libby P, Falk E et al.. From vulnerable plaque to vulnerable patient. A call for new definitions and risk assessment strategies: Part 1.  Circulation. 2003;  108 1664-1672
• 15 Naghavi M, Libby P, Falk E et al.. From vulnerable plaque to vulnerable patient. A call for new definitions and risk assessment strategies. Part II.  Circulation. 2003;  108 1772-1778
• 16 McCully K S. Vascular pathology of hyperhomocysteinemia: implications for the development of atherosclerosis.  Am J Pathol. 1969;  56 111-128
• 17 Kang S S, Wong P W, Malinov M R. Hyperhomocysteinemia as a risk factor for occlusive vascular disease.  Annu Rev Nutr. 1992;  12 279-298
• 18 Stampfer M J, Malinow M R, Willett W C et al.. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians.  JAMA. 1992;  268 877-881
• 19 Boers G H, Smals A G, Trijbels F J et al.. Heterozygozity for homocysteinuria in premature peripheral and cerebral occlusive arterial disease.  N Engl J Med. 1985;  313 709-715
• 20 Andersson A, Isaksson A, Hultberg B. Homocysteine export from erythrocytes and its implication for plasma sampling.  Clin Chem. 1992;  38 1311-1315
• 21 Lanfredini M, Fiorina P, Peca M G, Veronelli A, Mello A, Astorri E, Dall'Aglio P, Craveri A. Fasting and post-methionine load homocyst(e)ine values are correlated with microalbuminuria and could contribute to worsening vascular damage in non-insulin dependent diabetes mellitus patients.  Metabolism. 1998;  47 915-921
• 22 Andersson A, Brattstrom L, Israelsson B, Isaksson A, Hamfelt A, Hultberg B. Plasma homocysteine before and after methionine loading with regard to age, gender, and menopausal status.  Eur J Clin Invest. 1992;  22 79-87
• 23 Rasmussen K, Møller J, Lyngbak M, Pedersen A M, Dybkjaer L. Age- and gender-specific reference intervals for total homocysteine and methylalonic acid in plasma before and after vitamin supplementation.  Clin Chem. 1996;  42 630-636
• 24 Ganji V, Kafai M R. Third National Health and Nutrition Examination Survey. Demographic, health, lifestyle, and blood vitamin determinants of serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey, 1988-1994.  Am J Clin Nutr. 2003;  77 826-833
• 25 Rasmussen K, Møller J. Total homocysteine measurement in clinical practice.  Ann Clin Biochem. 2000;  37 627-648
• 26 Chambler J C, Obeid O A, Refsum H et al.. Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian, Asian and European men.  Lancet. 2000;  355 523-527
• 27 Lawrence J M, Petitti D B, Watkins M, Umekubo M A. Trends in serum folate after food fortification.  Lancet. 1999;  354 915-916
• 28 Brilakis E S, McConnell J P, Ballman K V, Klee G G, Berger P B. Lack of association between plasma homocysteine and angiographic coronary artery disease in the era of fortification of cereal grain flour with folic acid.  Atherosclerosis. 2002;  165 375-381
• 29 Vermeulen E GJ, Stedehouwer C DA, Twisk J WR et al.. Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial.  Lancet. 2000;  355 517-522
• 30 Kluijtmans L AJ, Young I S, Boreham C A et al.. Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults.  Blood. 2003;  101 2483-2488
• 31 Rifai N, Ridker P M. Proposed cardiovascular risk assessment algorithm using high-sensitive C-reactive protein and lipid screening.  Clin Chem. 2001;  47 28-30
• 32 Saito M, Ishimitsu T, Minami J, Ono H, Ohrui M, Matsuoka H. Relations of plasma high sensitive C-reactive protein to traditional cardiovascular risk factors.  Atherosclerosis. 2003;  167 73-79
• 33 Jager A, Kostense P J, Ruhe H G et al.. Microalbuminuria and peripheral arterial disease are independently predictors of cardiovascular and all-cause mortality, especially among hypertensive subjects: 5-year follow-up of the Hoorn Study.  Arterioscler Thromb Vasc Biol. 1999;  19 617-624
• 34 Ridker P M, Rifai N, Rose L, Buring J E, Cook N R. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.  N Engl J Med. 2002;  20 1557-1565
• 35 Usui S, Kakuuchi H, Okamoto M, Mizukami Y, Okazaki M. Differential reactivity of two homogeneous LDL-cholesterol methods to LDL and VLDL subfractions, as demonstrated by ultracentrifugation and HPLC.  Clin Chem. 2002;  48 1946-1954
• 36 Park R, Detrano R, Xiang M et al.. Combined use of computed tomography coronary calcium and C-reactive protein levels in predicting cardiovascular events in nondiabetic individuals.  Circulation. 2002;  106 2073-2077
• 37 Middleton J. Effect of analytical error on the assessment of cardiac risk by high-sensitive C-reactive protein and lipid screening model.  Clin Chem. 2002;  48 1955-1962
• 38 Kharbanda R K, Walton B, Allen M, Hingorani A D, Vallance P. Prevention of inflammation-induced endothelial dysfunction by the vasculo-protective action of aspirin.  Circulation. 2002;  105 2600-2604
• 39 Kent S M, Flaherty P J, Coyle L C, Markwood T T, Yaylor A J. Effect of atorvastatin and pravastatin on serum C-reactive protein.  Am Heart J. 2003;  145 e8
• 40 Dufaux B, Order U, Geyer H, Hollmann W. C-reactive protein serum concentrations in well-trained athletes.  Int J Sports Med. 1984;  5 102-106
• 41 Ford E S. Does exercise reduce inflammation? Physical activity and C-reactive protein among U.S. adults.  Epidemiology. 2002;  13 561-568
• 42 Church T S, Barlow C E, Earnest C P, Kampert J B, Priest E L, Blair H. Associations between cardiovascular fitness and C-reactive protein in men.  Arterioscler Thromb Vasc Biol. 2002;  22 1869-1876