Case Study: Chris Arden Peripheral Arterial Disease
Patient Presentation Diane is a 65-year-old retired school teacher She complains of left calf pain when walking 50 metres; the pain goes away after she rests for 5 minutes No other complaints
History NSTEMI 20 months ago Hypertension Type 2 diabetes (diagnosed 5 years ago) Hyperlipidaemia No family history of diabetes or cardiovascular disease Ex-smoker NSTEMI: non-st-elevation myocardial infarction
Medications ASA 75 mg/day Ramipril 10 mg/day Metformin 500 mg tds Atorvastatin 20 mg/day Bisoprolol 5 mg od ASA: acetylsalicylic acid
Physical Examination BMI: 29 kg/m 2 Waist circumference: 104 cm BP in clinic: 128/72 mmhg HR 80 bpm Left femoral bruit Bilateral reduced pedal pulses
Laboratory Investigations FPG: 6.2 mmol/l A1C: 7.5% (59mmol/mol) Lipids: TC 4.9 mmol/l TG 2.1 mmol/l HDL-C 1.3 mmol/l (female) LDL-C 1.9 mmol/l TC/HDL-C < 4.0 Urine ACR: 1.9 mg/mmol Complete blood count within normal limits ECG normal FPG: fasting plasma glucose; A1C: hemoglobin A1C; TC: total cholesterol; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; ACR: albumin-to-creatinine ratio; ECG: electrocardiogram
Question 1 What is your initial diagnosis?
Key Points Patient presents with typical symptom of PAD (intermittent claudication) and has a number of risk factors for the disease Basic screening should include history and physical examination Non-invasive evaluation should include an ABI ABI: ankle-brachial index
Risk Factors for PAD Risk factors for PAD are similar to those for atherosclerosis in other beds and include: Non-Modifiable Age Male sex Family history Modifiable Elevated lipid levels Cigarette smoking Hypertension Sedentary lifestyle Obesity Diabetes Smoking and diabetes are the most predictive for development of symptomatic claudication Teo KK. Can J Cardiol. 2005;21(12):997 1006.
Munger MA et al. J Am Pharm Assoc. 2004;44(suppl 1):s5-s13. Atherothrombosis Can Manifest in Multiple Vascular Beds Atherothrombosis is a process that includes the following clinical consequences: Ischemic stroke, MI, and PAD Patients with atherothrombosis have thrombus formations that can manifest in multiple vascular beds throughout the body
Varied Presentation of PAD PAD can be silent or cause symptoms ranging from pain to critical limb ischemia Typical Intermittent claudication: pain, ache, cramp, numbness, muscle fatigue in calves, thighs or buttocks; exacerbated by exercise and relieved by rest Critical limb ischemia: rest pain, ulcers, gangrene Atypical Decreased walking ability: (speed or distance) for reasons other than classical symptoms of intermittent claudication Pain in other areas: e.g., general aching McDermott MM et al. JAMA 2001;286:1599-1606.
REACH Registry Atherothrombosis: Overlapping Manifestations of Disease The REACH Registry found overlapping manifestations of disease in patients with CAD, CVD, and PAD CAD 44.6% 8.4% 1.6% 1.2% 4.7% PAD CVD 16.6% 61% of PAD patients also had symptomatic disease in the coronary or cerebral circulation 40% of CVD patients also had symptomatic disease in the coronary or peripheral circulation 25% of CAD patients also had symptomatic disease in the cerebral or peripheral circulation 4.7% 18.3% of patients in the REACH Registry did not have manifestations of atherothrombosis, but were included based on risk factors CAD: coronary artery disease; CVD: cerebrovascular disease; PAD: peripheral arterial disease Bhatt DL, et al; for the REACH Registry Investigators. JAMA. 2006;295:180-189.
Increased Risk of PAD with Diabetes 25 20 19.9 * 22.4 * Prevalence of PAD (%) 15 10 5 12.5 * 0 Normal glucose tolerance Impaired glucose tolerance Diabetes Impaired glucose tolerance was defined as oral glucose tolerance test value 140 mg/dl <200 mg/dl. * P 0.05 vs. normal glucose tolerance. Lee AJ, et al. Br J Haematol. 1999;105:648 654.
Question 2 What additional investigations would you perform?
Key Points: Diagnosis of PAD History Edinburgh Questionnaire Physical examination Bruit Peripheral pulses Non-invasive tests ABI Arterial Duplex Adapted from Roussin A, et al. Can J Cardiol. 2005;21(12):997 1006.
Edinburgh Questionnaire Do you get a pain or discomfort in your leg(s) when you walk? YES (If patient answers no, then stop here) Does this pain ever begin when you are standing still or sitting? NO Do you get it when you walk uphill or hurry? YES Do you get it when you walk at an ordinary pace on level ground? YES (Answer may also be no depending on severity of claudication) What happens to it if you stand still? Pain usually disappears in 10 minutes or less (pain continuing for more than 10 minutes is not consistent with PAD) Where do you get this pain or discomfort? Patient marks calf and/or thigh and/or buttock (A positive diagnosis of PAD requires the responses indicated in yellow for all questions) Leng GC, et al. J Clin Epidemiol. 1992;45:1101 1109.
Measuring ABI RIGHT ABI Higher right-ankle pressure Higher arm pressure Right-arm systolic pressure Left-arm systolic pressure LEFT ABI Higher left-ankle pressure Higher arm pressure INTERPRETATION OF ABI >1.30 Noncompressible 0.91-1.30 Normal Right-ankle systolic pressure DP PT DP PT Left-ankle systolic pressure 0.41-0.90 0.00-0.40 Mild-to-moderate peripheral arterial disease Severe peripheral arterial disease Adapted from Roussin A, et al. Can J Cardiol 2005;21(12):997-1006.
Significance of ABI Values
GetABI: Mortality (All-cause) by ABI Category > 1.1 0.9 1.1 0.7 0.9 0.5 0.7 < 0.5 Diehm C. Presented at ESC Congress. Vienna, Austria. September 4, 2007.
Question 3 What if the patient s pedal pulses were palpable and there were no bruits? Would this change your diagnosis?
Key Point Palpable pedal pulses and an absence of femoral bruits do not preclude PAD
PAD Regardless of Claudication Value of physical examination relative to presence of PAD ITEM Sensitivity Specificity RR if present Reduced pedal pulses 68% 95% 27 Femoral bruit 29% 95% 5.7 Slow venous filling 23% 95% 4.1 Cold skin 10% 98% 5.8 Abnormal colour 35% 87% 2.8 Trophic changes 46% 46% 1.5 McGee SR, et al. Arch Intern Med. 1998;158:1357 1364.
Case Evolution Based on your clinical examination, you diagnose Diane with PAD. You perform further investigations and find that she has an ABI of 0.65, which confirms your diagnosis.
Question 4 How would you manage this patient s: a) claudication? b) overall vascular risk?
Key Points: Objectives of PAD Therapy Prevent death and disability Reduce risk of MI (PAD quadruples MI risk) Reduce risk of stroke (PAD triples stroke risk) Relieve symptoms Improve QOL Improve walking ability Save limbs Prevent major amputations Avoid tissue loss QOL: quality of life
Guidelines for PAD: Risk Reduction Strategies Non-pharmacologic Exercise Blood pressure control Lipid control Habits - Smoking Pharmacologic Antiplatelet therapy Angiotensin converting enzyme inhibitors (ACE-I) Diabetes control Hypertension control Statin use
Risk Factor Management Smoking cessation Weight reduction Regular physical activity LDL-C < 2.0 mmol/l Glycosylated hemoglobin < 6.5% (48mmol/mol) BP < 140/90 mmhg; < 130/80 mmhg in patients with diabetes Platelet inhibition Hiatt WR. N Engl J Med. 2001;344:1608-1621.
Guidelines for PAD: Pharmacologic Approach Medical therapies to reduce cardiovascular events in PAD CLASS OF AGENTS Statins ACE inhibitors Oral hypoglycemics or insulin Antiplatelet GRADE 1A 1A 2B 1A
Supervised Exercise in the Management of Symptomatic PAD Exercise prescription is fundamental for all patients with claudication Supervised programs have patients walk to the point of moderate pain, followed by rest and repeat exercise Benefit is observed as early as 4 weeks and continues to improve Anand SS, Turpie AGG, et al. Can J Cardiol. 2005;21(12):997 1006.
Take-Home Messages Patients with PAD are at increased risk of diffuse vascular disease (i.e. IHD and CVD) Screen for PAD through history (Edinburgh Questionnaire) and physical examination (femoral bruits and pedal pulses) Definitive diagnosis of PAD requires an ABI < 0.9 Aggressive risk factor management should be considered for all patients with diffuse vascular disease
1. Munger MA et al. J Am Pharm Assoc. 2004;44(suppl 1):s5-s13. 2. Libby P et al. Circulation. 2005;111:3481-3488. Pathophysiology of Atherothrombosis Atherosclerosis + Thrombus Formation Rupture of Fibrous Cap Normal artery Accumulation of lipids Inflammation Smooth muscle cell progression, plaque progression Erosion of Endothelium Erosion of Calcium Nodule Atherosclerosis leads to any number of four possible types of thrombus formation Intraplaque Hemorrhage