Early Arterial Disease of the Lower Extremities in Diabetes - Diagnostic Evaluation and Risk Markers

.......................................................................................................................................... 4 LIST OF PAPERS ................................................................................................................................. 5 SAMMANFATTNING PÅ SVENSKA ................................................................................................ 6 ABBREVIATIONS ............................................................................................................................... 8 INTRODUCTION ................................................................................................................................. 9 LOWER EXTREMITY ARTERIAL DISEASE (LEAD) .......................................................................................... 9 CLASSIFICATION AND CLINICAL STAGES OF LEAD ........................................................................................ 9 NATURAL COURSE OF LEAD ........................................................................................................................ 10 Asymptomatic LEAD ...................................................................................................................................11 Symptomatic LEAD (Intermittent claudication) ............................................................................11 Critical leg ischemia ....................................................................................................................................11 PATHOPHYSIOLOGY OF LEAD ...................................................................................................................... 12 Patients with diabetes ................................................................................................................................13 Mediasclerosis ................................................................................................................................................13 DIAGNOSTIC METHODS .................................................................................................................................. 13 RISK MARKERS AND RISK FACTORS FOR LEAD .......................................................................................... 17 Modifiable risk factors ...............................................................................................................................18 Non-modifiable risk factors .....................................................................................................................19 SCREENING, PREVENTION AND CLINICAL MANAGEMENT OF LEAD ......................................................... 20 RESEARCH QUESTIONS AND SPECIFIC AIMS ........................................................................ 21 METHODS ......................................................................................................................................... 22 STUDY COHORTS ............................................................................................................................................ 22 BLOOD PRESSURE MEASUREMENTS (STUDY IIV)..................................................................................... 23 BLOOD AND URINE CHEMISTRY (STUDY I-IV) ............................................................................................ 25 STATISTICAL ANALYSES ................................................................................................................................. 26 SUMMARY OF RESULTS ................................................................................................................ 27 DISCUSSION ...................................................................................................................................... 28 DIFFERENT DEFINITIONS OF LEAD ............................................................................................................. 28 REPRODUCIBILITY OF ABSOLUTE BLOOD PRESSURES VS. INDICES ............................................................ 30 MODIFIED ELEVATION TEST (“POLE –TEST”) ............................................................................................ 31 NOVEL CLINICAL AND BIOCHEMICAL BIOMARKERS AS PREDICTORS OF LEAD ....................................... 31 ASPECTS ON SCREENING FOR EARLY, ASYMPTOMATIC LEAD USING TOE BLOOD PRESSURE ................. 32 CONCLUDING REMARKS .............................................................................................................. 34 ACKNOWLEDGEMENTS ................................................................................................................ 36 REFERENCES .................................................................................................................................... 37