Unfortunately, all too often, we shy away from valuable history and background information regarding the overall health of the patient. Many of us ask about diseases such as diabetes and some will routinely inquire about alcohol and smoking history. However, few of us spend the necessary time to truly evaluate and integrate historical data such as lipid profiles, etc. For example, peripheral vascular disease (PVD) is one finding in which we must consider all the historical information that is available in order to conduct a proper evaluation of the patient. Intermittent claudication is one sequela of diabetes which is sometimes underappreciated with regards to its seriousness and impact on peripheral vascular disease. This is an area where the patient’s overall health plays a major role. Many patients who have peripheral arterial disease (PAD) also have diabetes as a contributing factor. Did you know the incidence of diabetes has increased 33 percent over the last 10 years? Did you know that diabetes is not one disease but rather a “syndrome” of many other components (including obesity, hypertension, dyslipidemia, hyperinsulemia, and hyperglycemia) related to insulin resistance? According to a recent JAMA article, based on self-reported data from 1991-1999, the prevalence of diagnosed diabetes has increased 41 percent while obesity has increased 61 percent.1 These increases are associated with the increase in PAD and its related diseases. Keep in mind the prevalence of coronary artery disease in peripheral vascular disease is ~ 55 percent.2 Intermittent claudication is the primary symptom of peripheral arterial disease, according to the third edition of Harrison Internal Medicine.3 It is caused by an arterial obstruction in the lower extremity due to atherosclerosis. The symptoms are characterized by pain, discomfort, fatigue and numbness that patients feel in the affected limb during walking yet the symptoms resolve after a few minutes of rest. Be Aware Of The Alarming Risk Correlations With Diabetes Interestingly enough, the risk factors associated with the development of peripheral atherosclerosis are similar to those associated with the development of coronary atherosclerosis. These risk factors include: genetics, obesity, diabetes, smoking, dyslipidemia, hypertension, hyperecoagulabilty, hyperhomocysteinemia and age.3 At the recent University of Texas ‘Diabetic Foot Update’ Conference in December, Dr. David Allie, Chief of Cardiothoracic and Endovascular Surgery at the Cardiovascular Institute of the South, remarked “PVD is a marker for death.” Dr. Allie noted that the diagnosis of PVD carries a worse 5-, 10- and 15-year prognosis than breast cancer or Hodgkin’s Disease. He confirmed that 55 percent of those with PVD die from heart failure. This concern alone certainly warrants a closer look at a new patient’s lab work – including his or her triglyceride and cholesterol status. A 1998 article in the New England Journal of Medicine confirms the correlation between diabetes and heart disease. The study followed 1,300 patients without diabetes and 1,059 patients with diabetes with a seven-year follow-up period. The results showed that patients with diabetes had a 20 percent incidence of myocardial infarction during the study period whereas there was only a 4 percent incidence among patients without diabetes.5 Another article in Diabetes Care found that the risk of coronary artery disease is increased two to four-fold in people who have type 2 diabetes.6 Cardiovascular disease is the cause of death in 75 to 80 percent of people with diabetes. In fact, 50 percent of patients with diabetes have significant atherosclerotic disease when their diabetes is diagnosed.7 You’ll find an increased prevalence of elevated lipid levels in patients with diabetes in almost all categories vs. non-diabetics. In 1994, the journal, Lancet, published a study revealing that patients placed on a lipid lowering medication had a 30 percent reduced risk for total mortality, a 42 percent lower risk of coronary mortality and a 34 percent lower risk of a coronary event.8 As physicians, we should raise questions about the patient’s control of these different risk factors. Results from multiple studies, including the Diabetes Control and Complications Trial (DCCT), showed an average weight loss of seven pounds (or 5 to 10 percent of body weight) improves diabetes control, decreases insulin resistance, decreases hepatic glucose production, and increases insulin secretion. There is much for the patient to gain from this knowledge, but it is up to us to process this information and deliver it in a way that can be understood. What About Trental And Pletal? There are several pharmacological agents you can use to treat intermittent claudication. Generally, you would combine these agents with diet, exercise and nutritional balancing measures. Trental (pentoxifylline) and Pletal (cilostazol) have both been shown to reduce the pain associated with intermittent claudication and allow patients to increase walking distance. Trental works at the level of the cell membrane in which red blood cells are made more pliable, thus allowing them to move through the vascular tree with less resistance. Pletal has many different pharmacological effects which combine to improve blood flow. The principal pharmacologic effects of Pletal are vasodilatation, reversible inhibition of platelet aggregation and increased cyclic AMP. In fact, a 12-week, multicenter, randomized, double-blind trial of Pletal noted the following effects: • inhibits thrombus formation; • produces vasodilatation; • increases blood flow; • increases HDL-cholesterol by 10 percent; • decreases triglycerides by 15 percent; and • inhibits (in vitro) vascular smooth muscle cell proliferation.10-11 Final Notes In conclusion, intermittent claudication and peripheral vascular disease are highly prevalent manifestations of atherosclerosis and are associated with high risk for a multitude of illnesses and even death. Unfortunately, many practitioners underestimate the impact of peripheral arterial disease and the importance of its proper diagnosis and treatment. We should be aggressive in regards to PAD and the need for the patient to have a full workup by their primary care physician to control the modifiable risk factors — including diet, exercise and smoking. We should also institute a supervised walking program and use the available pharmacologic agents to help patients walk longer. Finally, we should be more vigilant in our efforts to help patients reach their goals of pain-free ambulation, as we may very well be saving their lives. Dr. Steinberg (pictured) is an Assistant Professor in the Department of Orthopaedics / Podiatry Service at the University of Texas Health Science Center. He is also the Medical Director of the Texas Diabetes Institute Podiatry Clinic. Mr. Khan is a first-year resident at the University of Texas Health Science Center in San Antonio.
References 1. Mokdad et al. the continuing epidemics of obesity and diabetes in the US. JAMA.2001;286:1195-1200. 2. Gersh et al. Ann Surg 1984. 3. Harrison Internal Medicine 3rd edition. 4. Brand FN et al. diabetes, intermittent claudication and risk of cardiovascular events. The Framingham study. Diabetes 38:504-509; 1989. 5. Haffner SM et al. N Eng J Med. 1998; 339: 229. 6. ADA-Diabetes Care 1996; 5196-5102. 7. Grundy SM et al, diabetes care 1990 153-160. 8. Lancet 1994; 344:1383-1389. 9. Hirsch et al. the role of tobacco cessation, antiplatelet and lipid lowering therapies in the treatment of peripheral vascular disease. Vasc Med 2:243-251;1997. 10. FDA Advisory Committee meeting Dossier: cilostazol for use in patients with intermittent claudication. Otsuka America Pharmaceutical, Inc. Rockville, MD; 6/3/1998. 11. Elam et al, effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermediate claudication. Arterioscler Thromb Vasc Biol 18:1942-1947;1998.