Exp Clin Endocrinol Diabetes 2004; 112(4): 157-170
DOI: 10.1055/s-2004-817927
Review

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Diabetes and Cardiovascular Risk Evaluation and Management in Primary Care: Progress and Unresolved Issues

Rationale for a Nationwide Primary Care Project in GermanyS. Böhler1 , 2 , H. Glaesmer3 , D. Pittrow4 , H. Lehnert5 , G. K. Stalla6 , A. M. Zeiher7 , W. März8 , S. Silber9 , M. Wehling10 , G. Ruf11 , A. Reinecke3 , H.-U. Wittchen3 , 12
  • 1Institute of Clinical Psychology and Psychotherapy, Technical University of Dresden, Dresden, Germany
  • 2Internat. Med. Research, Pfizer GmbH, Freiburg, Germany
  • 3Institute of Clinical Psychology and Psychotherapy, Tech. University of Dresden, Dresden, Germany
  • 4Institute of Clinical Pharmacology, Research Fed. Public Health Sachsen, Tech. University of Dresden, Dresden, Germany
  • 5Department of Endocrinology and Metabolic Disorders, Otto-v.-Guericke-University Magdeburg, Magdeburg, Germany
  • 6Department of Endocrinology, Max Planck Institute of Psychiatry, Munich, Germany
  • 7Department of Cardiology/Nephrology, Johann-Wolfgang-Goethe-University Frankfurt, Frankfurt, Germany
  • 8Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
  • 9Society of German Cardiologists in Private Practice, Munich, Germany
  • 10Institute of Clinical Pharmacology Mannheim, University of Heidelberg, Mannheim, Germany
  • 11Clinical Research, Pfizer GmbH, Karlsruhe, Germany
  • 12Department of Clinical Psychology and Epidemiology, Max Planck Institute of Psychiatry, Munich, Germany
Further Information

Publication History

Received: June 23, 2003 First decision: September 10, 2003

Accepted: October 30, 2003

Publication Date:
04 May 2004 (online)

Abstract

This review highlights established and more recently recognized risk factors for coronary heart disease (CHD) relevant for patients seen in primary care, emphasizing the key role of diabetes mellitus type 2. Recent trends in risk factor research as well as current methods of risk stratification, and new systemic markers are discussed. Beyond the need for more forceful public health strategies to improve early recognition and intervention, the necessity of an integrated comprehensive investigation of the overall characteristics of cardiovascular disease, especially in primary care patients as a prerequisite for future concerted actions is pointed out. Based on this, a large-scale epidemiological investigation focusing on CHD and diabetes in the primary care sector is suggested.

References

  • 134 Abraira C, Colwell J A, Nuttall F Q, Sawin C T, Nagel N J, Comstock J P, Emanuele N V, Levin S R, Henderson W, Lee H S. Veterans Affairs Cooperative Study on glycemic control and complications in type II diabetes (VA CSDM). Results of the feasibility trial. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes.  Diabetes Care. 1995;  18 1113-1123
  • 132 Abraira C, Colwell J, Nuttall F, Sawin C T, Henderson W, Comstock J P, Emanuele N V, Levin S R, Pacold I, Lee H S. Cardiovascular events and correlates in the Veteran Affairs Diabetes Feasibility Trial. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes.  Arch Intern Med. 1997;  157 181-188
  • 1 Albert M A, Danielson E, Rifai N, Ridker P M. PRINCE Investigators . Effect of statin therapy on C-reactive protein levels. The Pravastatin Inflammation/CRP Evaluation (PRINCE): A randomized trial and cohort study.  JAMA. 2001;  286 64-70
  • 2 Antman E M, Cohen M, Bernink P J, McCabe C H, Horacek T, Papuchis G, Mautner B, Corbalan R, Radley D, Braunwald E. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making.  JAMA. 2000;  284 835-842
  • 3 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
  • 4 Assmann G, Schulte H. The Prospective Cardiovascular Münster (PROCAM) study. prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease.  Am Heart J. 1988;  116 1713-1724
  • 5 Audelin M C, Genest Jr J. Homocysteine and cardiovascular disease in diabetes mellitus.  Atherosclerosis. 2001;  159 497-511
  • 135 Azad N, Emanuele N V, Abraira C, Henderson W G, Colwell J, Levin S R, Nuttall F Q, Comstock J P, Sawin C T, Silbert C, Rubino F A. The effects of intensive glycemic control on neuropathy in the VA cooperative study on type II diabetes mellitus (VA CSDM).  J Diabetes Complications. 1999;  13 307-313
  • 6 Baltali M, Korkmaz M E, Kiziltan H T, Muderris I H, Ozin B, Anarat R. Association between postprandial hyperinsulinemia and coronary artery disease among non-diabetic women: a case control study.  Int J Cardiol. 2003;  88 215-221
  • 7 Beaglehole R, Magnus P. The search for new risk factors for coronary heart disease: occupational therapy for epidemiologists?.  Int J Epidemiol. 2002;  31 1117-1122
  • 8 Beckman J A, Creager M A, Libby P. Diabetes and atherosclerosis.  JAMA. 2002;  287 2570-2581
  • 9 Benjamin E J, Smith Jr S C, Cooper R S, Hill M N, Luepker R V. 33rd Bethesda Conference. Task Force #1: Magnitude of the prevention problem: opportunities and challenges.  J Am Coll Cardiol. 2002;  40 588-603
  • 10 Biasucci L M, Liuzzo G, Grillo R L, Caligiuri G, Rebuzzi A G, Buffon A, Summaria F, Ginnetti F, Fadda G, Maseri A. Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability.  Circulation. 1999;  99 855-860
  • 11 Boersma E, Pieper K S, Steyerberg E W, Wilcox R G, Chang W C, Lee K L, Akkerhuis K M, Harrington R A, Deckers J W, Armstrong P W, Lincoff A M, Califf R M, Topol E J, Simoons M L. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevations. Results from an international trial of 9461 patients.  Circulation. 2000;  101 2557-2567
  • 12 Bostom A G, Silbershatz H, Rosenberg I H, Selhub J, D'Agostino R B, Wolf P A, Jacques P F, Wilson P W. Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women.  Arch Int Med. 1999;  159 1077-1080
  • 13 Bothig S. WHO MONICA Project. Objectives and design.  Int J Epidemiol. 1998;  18 29-37
  • 14 Boyle J P, Honeycutt A A, Narayan K M, Hoerger T J, Geiss L S, Chen H, Thompson T J. Projection of diabetes burden through 2050: impact of changing demography and disease prevalence in the US.  Diabetes Care. 2001;  24 1936-1940
  • 16 Buono C, Come C E, Witztum J L, Maguire G F, Connelly P W, Carroll M, Lichtman A H. Influence of C3 deficiency on atherosclerosis.  Circulation. 2002;  105 3025-3031
  • 17 Califf R M, Woodlief L H, Harrell Jr F E, Lee K L, White H D, Guerci A, Barbash G I, Simes R J, Weaver W D, Simoons M L, Topol E J. Selection of thrombolytic therapy for individual patients: development of a clinical model.  Am Heart J. 1997;  133 630-639
  • 18 Cermak J, Key N S, Bach R R, Balla J, Jacob H S, Vercellotti G M. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor.  Blood. 1993;  82 513-520
  • 19 Cho E, Rimm E B, Stampfer M J, Willett W C, Hu F B. The impact of diabetes mellitus and prior myocardial infarction on mortality from all causes and from coronary heart disease in men.  JACC. 2002;  40 954-960
  • 20 Cleland J GF, Swedberg K, Cohen-Solal A, Cosin-Aguilar J, Dietz R, Follath F, Gavazzi A, Hobbs R, Korewicki J, Madeira H C, Preda I, van Gilst H, Widimsky J, Mareev for the Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of Cardiology V, Mason J, Freemantle N, Eastaugh J. for the Medicines Evaluation Group Centre for Health Economics University of York . The Euro Heart Failure Survey of the EUROHEART survey programme. A survey on the quality of care among patients with heart failure in Europe.  Eur J Heart Fail. 2000;  2 123-132
  • 21 Conroy R M, Pyörälä K, Fitzgerald A P, Sans S, Menotti A, De Backer G, De Bacquer D, Ducimetière P, Jousilahti P, Keil U, Njolstad I, Oganov R G, Thomsen T, Tunstall-Pedoe H, Tverdal A, Wedel H, Whincup P, Wilhelmsen L, Graham I M. on behalf of the SCORE project group . Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project.  Eur Heart J. 2003;  24 987-1003
  • 23 Dandona P, Aljada A, Mohanty P, Ghanim H, Hamouda W, Assian E, Ahmad S. Insulin inhibits intranuclear nuclear factor kappa B and stimulates I kappa B in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect?.  J Clin Endocrinol Metab. 2001;  86 3257-3265
  • 24 Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Gallimore J R, Pepys M B. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses.  BMJ. 2000;  321 199-204
  • 25 Dunstan D W, Zimmet P Z, Welborn T A, De Courten M P, Cameron A J, Sicree R A, Dwyer T, Colagiuri S, Jolley D, Knuiman M, Atkins R, Shaw J E. The rising prevalence of diabetes and impaired glucose tolerance: the Australian Diabetes, Obesity and Lifestyle Study.  Diabetes Care. 2002;  25 829-834
  • 26 Ebrahim S, Smith G D. Systematic review of randomized controlled trials of multiple risk factor interventions for preventing coronary heart disease.  BMJ. 1997;  314 1666-1674
  • 27 Eikelboom J W, Lonn E, Genest Jr J, Hankey G, Yusuf S. Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence.  Arch Intern Med. 1999;  131 363-375
  • 133 Emanuele N, Klein R, Abraira C, Colwell J, Comstock J, Henderson W G, Levin S, Nuttall F, Sawin C, Silbert C, Lee H S, Johnson-Nagel N. Evaluations of retinopathy in the VA Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VA CSDM). A feasibility study.  Diabetes Care. 1996;  19 1375-1381
  • 28 EUROASPIRE II Study Group . Lifestyle and risk factor management and use of drug therapies in coronary patients from 15 countries. Principal results from EUROASPIRE II Euro Heart Survey Programme.  Eur Heart J. 2001;  22 554-572
  • 29 Evans J MM, Wang J, Morris A D. Comparison of cardiovascular risk between patients with type 2 diabetes and those who had had a myocardial infarction: cross sectional and cohort studies.  BMJ. 2002;  324 939-942
  • 30 Falk E, Shah P K, Fuster V. Coronary plaque disruption.  Circulation. 1995;  92 657-671
  • 31 Fayad Z A, Fuster V, Nikolaou K, Becker C. Computed tomography and magnetic resonance imaging for noninvasive coronary angiography and plaque imaging. Current and potential future concepts.  Circulation. 2002;  106 2026-2034
  • 32 Festa A, D'Agostino Jr R, Howard G, Mykkaenen L, Tracy R P, Haffner S M. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS).  Circulation. 2000;  102 42-47
  • 33 Flegal K M, Carroll M D, Kuczmarski R J, Johnson C L. Overweight and obesity in the United States: prevalence and trends, 1960 - 94.  Int J Obes Relat Metab Disord. 1998;  22 39-47
  • 34 Fletcher G F. 33rd Bethesda Conference. Preventive cardiology: how can we do better? Introduction.  J Am Coll Cardiol. 2002;  40 584-585
  • 22 Froehlich M, Imhof A, Berg G, Hutchinson W L, Pepeys M B, Boeing H, Muche R, Brenner H, Koenig W. Association between C-reactive protein and features of the metabolic syndrome: a population-based study.  Diabetes Care. 2000;  23 1835-1839
  • 35 Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation.  N Engl J Med. 1999;  340 448-454
  • 137 Gaede P, Vedel P, Parvin H H, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study.  Lancet. 1999;  353 617-622
  • 36 Gaede P, Vedel P, Larsen N, Jensen G V, Parving H H, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.  N Engl J Med. 2003;  348 383-393
  • 37 Galobardes B, Costanza M C, Bernstein M S, Delhumeau C H, Morabia A. Trends in risk factors for the major ‘lifestyle-related diseases’ in Geneva, Switzerland, 1993 - 2000.  Ann Epidemiol. 2003;  13 537-540
  • 38 Ginsberg H N, Stalenhoef A FH. The metabolic syndrome: targeting dyslipidemia to reduce coronary risk.  J Cardiovasc Risk. 2003;  10 121-128
  • 39 Goldstein B J. A Symposium: Evolution of type 2 Diabetes mellitus management.  Am J Cardiol. 2002;  90 1G-2G
  • 40 Goraya T Y, Leibson C L, Palumbo P J, Weston S A, Killian J M, Pfeifer E A, Jacobsen S J, Frye R L, Roger V L. Coronary atherosclerosis in diabetes mellitus, a population-based autopsy study.  JACC. 2002;  40 946-953
  • 41 Graham I M, Daly L E, Refsum H M, Robinson K, Brattstrom L E, Ueland P M, Palma-Reis R J, Boers G H, Sheahan R G, Israelsson B, Uiterwaal C S, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht J C, de Valk H W, Sales Luis A C, Parrot-Rouland F M, Tan K S, Higgins I, Garcon D, Andria G. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project.  JAMA. 1997;  277 1775-1781
  • 42 Grundy S M, Bazzarre T, Cleeman J, D'Agostino Sr R B, Hill M, Houston-Miller N, Kannel W B, Krauss R, Krumholz H M, Lauer R M, Ockene I S, Pasternak R C, Pearson T, Ridker P M, Wood D. Prevention Conference V. Beyond secondary prevention: identifying the high-risk patient for primary prevention. Medical office assessment. Writing group I.  Circulation. 2000;  101 3-11
  • 43 Grundy S M, Pasternak R, Greenland P, Smith Jr S, Fuster V. AHA/ACC scientific statement: Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology.  J Am Coll Cardiol. 1999;  34 1348-1359
  • 44 Grundy S M. Primary prevention of coronary heart disease. Integrating risk assessment with intervention.  Circulation. 1999;  100 988-998
  • 45 Haffner S M, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in non-diabetic subjects with and without prior myocardial infarction.  N Engl J Med. 1998;  339 229-234
  • 46 Harjai K J. Potential new cardiovascular risk factors: left ventricular hypertrophy, homocysteine, lipoprotein(a), triglycerides, oxidative stress, and fibrinogen.  Ann Intern Med. 1999;  131 376-386
  • 47 Harris M I, Flegal K M, Cowie C C, Eberhardt M S, Goldstein D E, Little R R, Wiedmeyer H M, Byrd-Holt D D. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U. S. adults: the third National Health and Nutrition Examination Survey, 1988 - 1994.  Diabetes Care. 1998;  21 518-524
  • 48 Harris R, Donahue K, Rathore S S, Frame P, Woolf S H, Lohr K N. Screening adults for type 2 diabetes: a review of the evidence for the U. S. Preventive Services Task Force.  Ann Intern Med. 2003;  138 215-229
  • 49 Hasdai D, Behar S, Wallentin L, Danchin N, Gitt A K, Boersma E, Fioretti P M, Simoons M L, Battler A. A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin: the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS).  Eur Heart J. 2002;  23 1190-1201
  • 50 Haverkate F, Thompson S G, Pyke S D, Gallimore J R, Pepys M B. Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.  Lancet. 1997;  349 462-466
  • 51 Heeschen C, Dimmeler S, Hamm C W, van den Brand M J, Boersma E, Zeiher A M, Simoons M L, Study Investigators C APTURE. Soluble CD40 ligand in acute coronary syndromes.  N Engl J Med. 2003;  348 1104-1111
  • 52 Helmert U, Shea S. Antihypertensive treatment and serum cholesterol: results of population-based surveys in the German Cardiovascular Prevention Study.  Rev Environ Health. 1997;  12 253-260
  • 53 Hoffmeister H, Mensink G B, Stolzenberg H. National trends in risk factors for cardiovascular disease in Germany.  Pre Med. 1994;  23 197-205
  • 54 Hu F B, Stampfer M J, Haffner S M, Solomon C G, Willett W C, Manson J E. Elevated risk of cardiovascular disease prior to clinical diagnosis of type 2 diabetes.  Diabetes Care. 2002;  25 1129-1134
  • 55 Hutchinson W L, Koenig W, Frohlich M, Sund M, Lowe G D, Pepys M B. Immunoradiometric assay of circulating C-reactive protein: age-related values in the adult general population.  Clin Chem. 2000;  46 934-938
  • 56 Imhof A, Froehlich M, Brenner H, Boeing H, Pepys M B, Koenig W. Effect of alcohol consumption on systemic markers of inflammation.  Lancet. 2001;  357 763-767
  • 57 Inelmen E M, Sergi G, Coin A, Miotto F, Peruzza S, Enzi G. Can obesity be a risk factor in elderly people?.  Obesity Reviews. 2003;  4 147-155
  • 58 Jacobs Jr D R, Adachi H, Mulder I, Kromhout D, Menotti A, Nissinen A, Blackburn H. for the Seven Countries Study Group . Cigarette smoking and mortality risk: twenty-five-year follow-up of the Seven Countries Study.  Arch Intern Med. 1999;  159 733-740
  • 59 Jialal I, Stein D, Balis D, Grundy S M, Adams-Huet B, Devaraj S. Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels.  Circulation. 2001;  103 1933-1935
  • 60 Kannel W B, Gee M CDL. Diabetes and glucose tolerance risk factors for cardiovascular disease: the Framingham Study.  Diabetes Care. 1979;  2 120-126
  • 61 Khot U N, Khot M B, Bajzer C T, Sapp S K, Ohman E M, Brener S J, Ellis S G, Lincoff A M, Topol E J. Prevalence of conventional risk factors in patients with coronary heart disease.  JAMA. 2003;  290 898-904
  • 62 King H, Aubert R E, Herman W H. Global burden of diabetes, 1995 - 2025: prevalence, numerical estimates, and projections.  Diabetes Care. 1998;  21 1414-1431
  • 127 Knatterud G L, Meinert C L, Klimt C R, Osborne R K, Martin D B. Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. IV. A preliminary report on phenoformin results.  JAMA. 1971;  217 777-784
  • 128 Knatterud G L, Klimz C R, Levin M E, Jacobson M E, Goldner M G. Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VII. Mortality and selected nonfatal events with insulin treatment.  JAMA. 1978;  240 37-42
  • 63 Kuulasmaa K, Tunstall-Pedoe H, Dobson A, Fortmann S, Sans S, Tolonen H, Evans A, Ferrario M, Tuomilehto J. Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations.  Lancet. 2000;  355 675-687
  • 64 LaMonte M J, Durstine J L, Yanowitz F G, Lim T, DuBose K D, Davis P, Ainsworth B E. Cardiorespiratory fitness and C-reactive protein among a tri-ethnic sample of women.  Circulation. 2002;  106 403-406
  • 65 Lempiainen P, Mykkanen L, Pyorala K, Laakso M, Kuusisto J. Insulin resistance syndrome predicts coronary heart disease events in elderly nondiabetic men.  Ciruclation. 1999;  100 123-128
  • 136 Levin S R, Coburn J W, Abraira C, Henderson W G, Colwell J A, Emanuele N V, Nuttall F Q, Sawin C T, Comstock J P, Silbert C K. Effect of intensive glycemic control on microalbuminuria in type 2 diabetes. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes Feasibility Trial Investigators.  Diabetes Care. 2000;  23 1478-1485
  • 66 Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Prospective studies collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.  Lancet. 2002;  360 1903-1913
  • 67 Lind L. Circulating markers of inflammation and atherosclerosis.  Atherosclerosis. 2003;  169 203-214
  • 68 Lopez A D, Murray C JL. The global burden of disease, 1990 - 2020.  Nat Med. 1998;  4 1241-1243
  • 69 LRC Program I . Lipid Research Clinics Program: The Lipid Research Clinics Coronary Primary Prevention Trial results. I: Reduction in the incidence of coronary heart disease.  JAMA. 1984;  251 351-364
  • 70 LRC Program II . Lipid Research Clinics Program: The Lipid Research Clinics Coronary Primary Prevention Trial results. II: The relationship of reduction in incidence of coronary heart disease to cholesterol lowering.  JAMA. 1984;  251 365-374
  • 71 Messerli F H, Grossman E, Goldbourt U. Antihypertensive therapy in diabetic hypertensive patients.  Am J Hypertens. 2001;  14 12S-16S
  • 72 Morrow D A, Antman E M, Charlesworth A, Cairns R, Murphy S A, de Lemos J A, Giugliano R P, McCabe C H, Braunwald E. TIMI risk score for ST-elevation myocardial infarction: A convenient, bedside, clinical score for risk assessment at presentation: An intravenous nPA for treatment of infarcting myocardium early II trial substudy.  Circulation. 2000;  102 2031-2037
  • 73 Mudd S H, Skovby F, Levy H L, Pettigrew K D, Wilcken B, Pyeritz R E, Andria G, Boers G H, Bromberg I L, Cerone R. The natural history of homocystinuria due to cystathionine β-synthase deficiency.  Am J Hum Genet. 1985;  37 1-31
  • 74 NCEP ATP III .National Cholesterol Education Program: 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). NIH Pub. No. 02/5215. Bethesda, MD; National Heart, Lung, and Blood Institute 2002: 284 pages
  • 75 Neal B, MacMahon S, Chapman N. for the Blood Pressure Lowering Treatment Trialists' Collaboration . Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists' Collaboration.  Lancet. 2000;  356 1955-1964
  • 76 Newman A B, Siscovick D S, Manolio T A, Polak J, Fried L P, Borhani N O, Wolfson S K. Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study.  Circulation. 1993;  88 837-845
  • 77 Norhammar A, Tenerz A, Nilsson G, Hamsten A, Efendic S, Ryden L, Malmberg K. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study.  Lancet. 2002;  359 2140-2144
  • 130 Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, Kojima Y, Furuyoshi N, Shichiri M. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study.  Diabetes Res Clin Pract. 1995;  28 103-117
  • 78 Pasceri V, Cheng J S, Willerson J T, Yeh E T, Chang J. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs.  Circulation. 2001;  103 2531-2534
  • 79 Pasceri V, Willerson J T, Yeh E T. Direct proinflammatory effect of C-reactive protein on human endothelial cells.  Circulation. 2000;  102 2165-2168
  • 80 Pekkanen J, Linn S, Heiss G. Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without pre-existing cardiovascular disease.  N Engl J Med. 1990;  322 1700-1707
  • 81 Pyorala M, Miettinen H, Laakso M, Pyorala K. Hyperinsulinemia predicts coronary heart disease risk in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study.  Circulation. 1998;  98 398-404
  • 82 Reusch J EB. Current concepts in insulin resistance, type 2 diabetes mellitus, and the metabolic syndrome.  Am J Cardiol. 2002;  90 (Suppl) 19G-26G
  • 83 Ridker P M, Buring J E, Shih J, Matias M, Hennekens C H. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women.  Circulation. 1998;  98 731-733
  • 84 Ridker P M, Cushman M, Stampfer M J, Tracy R P, Hennekens C H. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.  N Engl J Med. 1997;  336 973-979
  • 85 Ridker P M, Rifai N, Clearfield M, Downs J R, Weis S E, Miles J S, Gotto Jr A M. Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events.  N Engl J Med. 2001;  344 1959-1965
  • 86 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;  347 1557-1565
  • 87 Rifai N, Tracy R P, Ridker P M. Clinical efficacy of an automated high-sensitive C-reactiv protein assay.  Clin Chem. 1999;  45 2136-2141
  • 88 Rosenson R S, Koenig W. Utility of inflammatory markers in the management of coronary artery disease.  Am J Cardiol. 2003;  92 (Suppl) 10i-18i
  • 89 Rosenson R S, Staffileno B A, Tangney C C. Effects of tourniquet technique, order of draw, and sample storage on plasma fibrinogen.  Clin Chem. 1998;  44 688-690
  • 90 Ross R. Atherosclerosis - an inflammatory disease.  New Engl J Med. 1999;  340 115-126
  • 91 Rossouw J E, Lewis B, Rifkind B M. The value of lowering cholesterol after myocardial infarction.  N Engl J Med. 1990;  323 1112-1119
  • 92 Ruof J, Klein G, Maerz W, Wollschlaeger H, Neiss A, Wehling M. Lipid-lowering medication for secondary prevention of coronary heart disease in a German outpatient population: the gap between treatment guidelines and real life treatment patterns.  Preventive Medicine. 2002;  35 48-53
  • 93 Sato I, Nishida M, Okita K, Nishijima H, Kojima S, Matsumura N, Yasuda H. Beneficial effect of stopping smoking on future cardiac events in male smokers with previous myocardial infarction.  Jpn Circ J. 1992;  56 217-222
  • 94 Sebastio G, Sperandeo M P, Panico M, de Franchis R, Kraus J P, Andria G. The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations.  Am J Hum Gen. 1995;  56 1324-1333
  • 95 Seeman T E, McEwen B S, Rowe J W, Singer B H. Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging.  PNAS. 2001;  98 4770-4775
  • 96 Semb A G, van Wissen S, Ueland T, Smilde T, Waehre T, Tripp M D, Froland S S, Kastelein J J, Gullestad L, Pedersen T R, Aukrust P, Stalenhoef A F. Raised serum levels of soluble CD40 ligand in patients with familial hypercholesterolemia: downregulatory effect of statin therapy.  J Am Coll Cardiol. 2003;  41 275-279
  • 97 Sever P S, Dahlof B, Poulter N R, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen S E, Kristinsson A, McInnes G T, Mehlsen J, Nieminen M, O'Brien E, Ostergren J. ASCOT investigators . Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial.  Lancet. 2003;  361 1149-1158
  • 15 Sharma A M, Bramlage P, Wittchen H-U, Pittrow D, Kirch W, Wittchen H U. Prevalence of overweight and obesity in primary care patients in Germany. 2003 Annual Meeting of the North American Society for the Study of Obesity (NAASO), Ft. Lauderdale, USA, October 11 - 15, 2003.  Obes Res. 2003;  11 (Suppl) A127
  • 98 Sharma A M, Wittchen H-U, Krause P, Kirch W, Pittrow D, Ritz E, Göke B, Lehnert H, Tschöpe D, Höfler M, Pfister H, Bramlage P, Unger T. High prevalence and poor control of hypertension in primary care: Cross sectional study.  J Hypertens. 2004;  22 1-9
  • 131 Shichiri M, Kishikawa H, Ohkubo Y, Wake N. Long-term results of the Kumamoto Study on optimal diabetes control in type 2 diabetic patients.  Diabetes Care. 2000;  23 (Suppl 2) B 21-29
  • 99 Sniderman A D, Furberg C D, Keech A, Roeters van Lennep J E, Frohlich J, Jungner I, Walldius G. Apolipoproteins versus lipids as indices of coronary risk and as targets for statin treatment.  Lancet. 2003;  361 777-780
  • 100 Stamler J, Stamler R, Neaton J D, Wentworth D, Daviglus M L, Garside D, Dyer A R, Liu K, Greenland P. Low risk-factor profile and long-term cardiovascular and non cardiovascular mortality and life expectancy. Findings for 5 large cohorts of young adult and middle-aged men and women.  JAMA. 1999;  282 2112-2118
  • 101 Stamler J, Vaccaro O, Neaton J D, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial.  Diabetes Care. 1993;  16 434-444
  • 102 Stamler J, Wentworth D, Neaton J D. Is the relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356 222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT).  JAMA. 1986;  256 2823-2828
  • 103 Stec J J, Silbershatz H, Tofler G H, Matheney T H, Sutherland P, Lipinska I, Massaro J M, Wilson P F, Muller J E, D'Agostino Sr R B. Association of fibrinogen with cardiovascular risk factors, and cardiovascular disease in the Framingham offspring population.  Circulation. 2000;  102 1634-1638
  • 104 Sytkowski P A, D'Agostino R B, Belanger A J, Kannel W B. Secular trends in long-term sustained hypertension, long-term treatment, and cardiovascular mortality. The Framingham Heart Study 1950 to 1990.  Circulation. 1996;  93 697-703
  • 105 Tchernof A, Nolan A, Sites C K, Ades P A, Poehlman E T. Weight loss reduces C-reactive protein levels in obese postmenopausal women.  Circulation. 2002;  105 564-569
  • 106 The GRACE investigators . Rationale and design of the GRACE (Global Registry of Acute Coronary Events) project: a multinational registry of patients hospitalized with acute coronary syndromes.  Am Heart J. 2001;  141 190-199
  • 138 The World Health Report . Conquering suffering, enriching humanity.  World Health Forum. 1997;  18 248-260
  • 107 Tillet W S, Francis T. Serological reactions in pneumonia with a non-protein somatic fraction of pneumococcus.  J Exp Med. 1930;  52 561-571
  • 108 Torzewski M, Rist C, Mortensen R F, Zwaka T P, Bienek M, Waltenberger J, Koenig W, Schmitz G, Hombach V, Torzewski J. C-reactive protein in the arterial intima. Role of C-reactive protein receptor - dependent monocyte recruitment in atherogenesis.  Arterioscler Thromb Vasc Biol. 2000;  20 2094-2099
  • 109 Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, Arveiler D, Rajakangas A M, Pajak A. Myocardial infarction and coronary deaths in the World Health organization MONICA Project. Registration procedures, event rates and case-fatality rates in 38 populations from 21 countries in four continents.  Circulation. 1994;  90 583-612
  • 110 UKPDS 33 . UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).  Lancet. 1998;  352 837-853
  • 129 UKPDS 34 . Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group.  Lancet. 1998;  352 854-865
  • 111 UKPDS 38 . Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes (UKPDS 38).  BMJ. 1998;  317 703-713
  • 112 Vaessen N, Heutink P, Janssen J A, Witteman J CM, Testers L, Hofman A, Lamberts S WJ, Oostra B A, Pols H AP, van Duijn C M. A polymorphism in the gene for IGF-I. Functional properties and risk for type 2 diabetes and myocardial infarction.  Diabetes. 2001;  50 637-642
  • 113 Van den Hoogen P C, Seidell J C, Menotti A, Kromhout D. Blood pressure and long-term coronary heart disease mortality in the Seven Countries study: implications for clinical practice and public health.  Eur Heart J. 2000;  21 1639-1642
  • 114 Van Wissen S, Trip M D, Smilde T J, de Graaf J, Stalenhoef A F, Kastelein J J. Differential hs-CRP reduction in patients with familial hypercholesterolemia treated with aggressive or conventional statin therapy.  Atherosclerosis. 2002;  165 361-366
  • 115 Vinicor F, Bowman B, Engelgau M. Diabetes prevention needed.  Lancet. 2003;  361 544
  • 116 Wald D S, Law M, Morris J K. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis.  BMJ. 2002;  325 1202-1206
  • 117 Walter D H, Fichtlscherer S, Britten M B, Rosin P, Auch-Schwelk W, Schachinger V, Zeiher A M. Statin therapy, inflammation and recurrent coronary events in patients following coronary stent implantation.  J Am Coll Cardiol. 2001;  38 2006-2012
  • 118 Welch G N, Loscalzo J. Homocysteine and atherothrombosis.  N Engl J Med. 1998;  338 1042-1050
  • 119 Wilson P W, D'Agostino R B, Levy D, Belanger A M, Silbershatz H, Kannel W B. Prediction of coronary heart disease using risk factor categories.  Circulation. 1998;  97 1837-1847
  • 120 Wittchen H-U, Krause P, Höfler M, Pfister H, Küpper B, Pittrow D, Bramlage P, Unger T, Sharma A M, Ritz E, Göke B, Lehnert H, Tschöpe D, Kirch W. Objective, design and methodology of the hypertension and diabetes risk screening and awareness - (HYDRA) study. Wittchen H-U The Hypertension and Diabetes Risk Screening and Awareness (HYDRA) Study. Fortschritte der Medizin 121 (Special Issue I/2003). First Ed. München; Urban & Voge 2003: 2-44
  • 121 Wong N D, Wilson P W, Kannel W B. Serum cholesterol as a prognostic factor after myocardial infarction: the Framingham Study.  Ann Intern Med. 1991;  115 687-693
  • 122 Wood D, De Backer G, Faergeman O, Graham I, Mancia G, Pyorala K. Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention.  Atherosclerosis. 1998;  140 199-270
  • 123 Yamagishi K, Iso H, Kitamura A, Sankai T, Tanigawa T, Naito Y, Sato S, Imano H, Ohira T, Shimamoto T. Smoking raises the risk of total and ischemic strokes in hypertensive men.  Hypertens Res. 2003;  26 209-217
  • 124 Yasojima K, Schwab C, McGeer E G, McGeer P L. Generation of C-reactive protein and complement components in atherosclerotic plaques.  Am J Pathol. 2001;  158 1039-1051
  • 125 Zanchetti A, Hansson L, Dahloef B, Elmfeldt D, Kjeldsen S, Kolloch R, Larochelle P, McInnes G T, Mallion J-M, Ruilope L, Wedel H. on behalf of the HOT Study Group . Effects of individual risk factors on the incidence of cardiovascular events in the treated hypertensive patients of the Hypertension Optimal Treatment Study.  Journal of Hypertension. 2001;  19 1149-1159
  • 126 Zwaka T P, Hombach V, Torzewski J. C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis.  Circulation. 2001;  103 1194-1197

H. Glaesmer

Institute of Clinical Pharmacology Mannheim
University of Heidelberg

Theodor-Kutzer-Ufer 1 - 3

68167 Mannheim

Germany

Phone: + 4935146336985

Fax: + 49 3 51 46 33 69 84

Email: glaesmer@psychologie.tu-dresden.de

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