Blood pressure is the force exerted by the blood on the walls of the arteries. High blood pressure is known as hypertension (HT) and is commonly associated with vascular disease. HT is an independent risk factor for the development of PAD and is prevalent in patients with symptomatic disease. Approximately 75% of patients with intermittent claudication have HT compared with 50% in age-matched controls. High blood pressure is a major cause of atherosclerosis and a reduction of as little as 5mmHg can lower the risk of stroke by 34% and ischemic heart disease by 21%. The relation between PAD and hypertension is probably best correlated with improvement in symptoms of claudication and events in coronary and cerebrovascular disease.
Peripheral arterial disease (PAD) is a common circulatory problem in which narrowed arteries reduce blood flow to limbs. Occurring mostly in the legs, PAD can also be found in arteries that supply blood to your head, arms, kidneys, and stomach. It can be caused by a build-up of plaque on the walls of the arteries, a condition called atherosclerosis, or inflammation and clotting in the blood vessels. It causes reduced blood flow to various tissues, which can result in symptoms and signs of ischemia. Often the most distressing symptom of lower limb ischemia is severe pain brought on by exercise and relieved by rest (intermittent claudication).
Definition of Peripheral Arterial Disease (PAD)
Peripheral artery disease (PAD) has been defined as a common but often unrecognized systemic disease, being a subset of atherosclerosis and a marker for widespread cardiovascular disease. The most widely used definition is that proposed by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA): “PAD is atherosclerotic occlusive disease of the lower extremities.” This definition has been updated with an abnormal ankle-brachial pressure index (ABPI) as the first stage of PAD. An ABPI of less than 0.90 has a sensitivity of 90% and a specificity of 98% for the detection of >50% stenosis in at least one lower limb artery (type IIa evidence). In this guideline, PAD generally refers to a disease of the arteries rather than the microcirculation. The TASC II document focuses on the end stage of disease and patients with critical limb ischemia (CLI). CLI has been defined as ischemic rest pain or ischemic ulcers or gangrene, and an ABPI of less than 0.40. This is a clear and important distinction, but it is acknowledged that PAD is a progressive disease and the overall management of the risk factors, medical therapy, and endovascular treatment or surgical reconstruction may alter the natural history of PAD, preventing some patients from reaching the CLI stage. Various other definitions using symptoms or clinical signs for intermittent claudication, the most common symptom of PAD, have been used in the past, but generally these are insensitive and non-specific for the presence or severity of PAD. An accurate definition of the disease state, often asymptomatic with a risk of progression to limb and life-threatening states, is important in both clinical practice and also for the purposes of clinical trials or epidemiological studies.
Importance of Blood Pressure Management
In patients with PAD, the optimum level of blood pressure and the best treatment strategy are largely undefined. No randomized trials have specifically addressed blood pressure management in PAD patients and few observational studies have been published. This contrasts with the extensive literature on antiplatelet therapy and lipid-lowering therapy in PAD, although the latter was also relatively sparse until recent years. In this regard, the ongoing Heart Protection Study would not have been possible without an extensive previous literature. High rates of coexisting cardiovascular and renal disease have often resulted in PAD patients being excluded from trials of blood pressure-lowering therapy, and the available evidence is predominantly from subgroup analyses. Nonetheless, certain points are worth emphasizing.
Given the high risk of MACE, poorer prognosis, and the adverse prognostic effect of concomitant diabetes, hypertensive patients with PAD would be expected to derive particular benefit from aggressive blood pressure-lowering therapy. Unfortunately, the evidence is lacking. In terms of macrovascular disease prevention, two landmark trials confirmed the value of blood pressure-lowering therapy in reducing the incidence of stroke and major cardiovascular events, predominantly in patients with coronary artery disease. However, neither trial included patients with PAD, and the recent Hypertension Optimal Treatment (HOT) study did not reach its prespecified target of involving PAD patients in a subgroup analysis of outcome according to different levels of blood pressure.
The importance of blood pressure management in peripheral arterial disease is poorly appreciated. The presence of hypertension is a significant adverse prognostic factor in patients with claudication or critical limb ischemia. In patients with intermittent claudication, hypertension is associated with a more rapid progression to limb ischemia and a higher incidence rate of myocardial infarction and/or stroke. In patients with critical limb ischemia, hypertension is associated with a higher incidence of major adverse cardiovascular events (MACE) and a trend toward a higher mortality rate. Diabetes is also an important adverse prognostic factor in patients with PAD. In hypertensive patients with PAD, established diabetic nephropathy is the second most frequent cause of end-stage renal failure. It is uncommon for such patients to receive renal replacement therapy and long-term survival rates are lower than in patients with other causes of end-stage renal disease. In a retrospective cohort study based on the United States Renal Data System, diabetes was associated with poorer patient survival irrespective of the presence of cardiovascular or renal disease.
Risk Factors for Peripheral Arterial Disease
The significance of aggressive treatment of PAD is largely due to the fact that many of the risk factors for this condition are also risk factors for coronary artery disease. In fact, many studies have demonstrated that patients with PAD are at very high risk for myocardial infarction (MI) and ischemic strokes. For this reason, those who are treating PAD must also consider the systemic effects the disease will have on a patient and work to prevent complications in other vascular beds. This fact assumes even greater importance when one considers the shortened lifespan and loss of independence suffered by patients with advanced PAD and its associated risk factors. Because patients with PAD have such a high risk and often suffer from other diseases, it is extremely important to focus on prevention and early intervention in this population. Smoking is the single greatest risk factor for PAD and has been shown to increase the risk of the disease by 8 to 10 times over that of nonsmokers. It has been estimated that 95% of those with intermittent claudication are current or former smokers and the dose-dependent relationship this factor has with the severity of the disease means that the physician must question the patient on pack-years and provide strong encouragement to quit. It has also been demonstrated that former smokers eventually regress to the same risk as non-smokers and never develop the disease if they are able to quit.
Smoking
Development of any disease, including PAD, is invariably influenced by the presence of various risk factors. Identification and modification of risk factors for PAD is an essential part of management of the diseased patient. Smoking is the strongest risk factor for development of PAD. Smokers have approximately 2-3 fold increased risk of developing PAD compared to non-smokers. The association between smoking and PAD is dose related, with heavy smokers having the highest risk of PAD. Cessation of smoking is associated with a regression in the risk of developing PAD. Former smokers have been shown to have similar risk for PAD as non-smokers in some studies. Smokers have an increased risk of claudication and also an increased risk of limb loss and amputation. This is probably related to the effects of smoking on atherosclerosis and also the effects of smoking on platelet function and coagulation. High and low rates of passive smoke exposure are associated with a 2-fold increased prevalence of PAD and an increase in the rate of progression of PAD. Cigarette smoking is a well-recognized risk factor for CVD. It is a major cause of ischemic heart disease, myocardial infarction, peripheral vascular disease and cerebrovascular disease. Collectively, these diseases are the most common cause of death in the UK. The impact of smoking on the development of peripheral vascular disease (PVD) has been clearly demonstrated in several epidemiological studies.
Diabetes
An example of this is glycated hemoglobin, which identifies diabetics with poor glucose control. These molecules cause damage to the arterial walls and accelerate atherosclerosis. High levels of sugar in the bloodstream also cause damage to the endothelium, which affects the production of nitric oxide, a molecule that helps to prevent atherosclerosis by dilating blood vessels and reducing platelet aggregation. Damage to the nitric oxide production pathway leads to increased platelet aggregation and less vasodilation. This increases the diabetic’s risk of developing coronary artery disease and PAD.
An autopsy study of sudden death victims discovered that 87% of diabetics had coronary atherosclerosis, and two-thirds of them had extensive disease. What is more telling is that the extent of atherosclerosis was comparable to non-diabetics who had already suffered a myocardial infarction. Damage to the blood vessels in diabetics occurs through many mechanisms, one of them being glycation. Several sugars in the body have abnormal chemical bonds with proteins, and the end product is molecules called advanced glycation end products (AGEs). These molecules in the bloodstream cause inflammation, and when they bind to proteins they alter their structure and function.
A multitude of studies have shown that diabetics, either type I or type II, have a much higher incidence of developing peripheral arterial disease (PAD). The Framingham study found that diabetic patients had a 2.21 relative risk of developing PAD compared to non-diabetics. In addition, the ACC/AHA guidelines have determined that diabetes is a coronary heart disease risk equivalent. One of the main reasons for the higher incidence of PAD in diabetics is their propensity to develop atherosclerosis.
High Cholesterol
High cholesterol is a risk factor for peripheral arterial disease. Unfortunately, there is a significant lack of high-quality data demonstrating the impact of lipid management on all-cause and cardiovascular mortality in patients with PAD. Despite this, there is a strong likelihood that treatment of hyperlipidemia with lifestyle measures and drugs will also reduce the risk of progression of lower limb and other atherosclerotic disease, as well as reducing the risk of ischemic events and improving cardiovascular mortality. High cholesterol in the blood contributes to the formation of plaque in the walls of peripheral arteries and is a leading cause of PAD. This occurs when the cholesterol buildup forms an atheroma, stiffening the artery walls and narrowing the lumen. High cholesterol is therefore a relevant risk factor for PAD, and its management is therefore important. In PAD patients, the risk of subsequent events or progression to revascularization was found to be 50% higher in those with total cholesterol levels >6.2 mmol/l. This study suggested that a reduction in cholesterol may prevent future ischemic events and impede the progression of lower limb disease and recommended an improvement in lipid management in patients with PAD to reduce the risk of future cardiovascular events. Although lipid management has not been studied as an isolated strategy in PAD, the high risk of atherothrombotic events and potential prevention of progression of PAD makes it a highly important intervention for these patients. Cholesterol-reducing medications are widely used in the treatment of patients with hyperlipidemia. HMG-CoA enzyme inhibitors or statins have been shown to reduce the risk of major cardiovascular events in patients with or without cardiovascular disease. High cholesterol is a risk factor for peripheral arterial disease, and while aggressive cholesterol-lowering therapies may not reverse the formation of atheroma in diseased arteries, it may reduce ischemic events by inhibiting plaque progression and stabilizing vulnerable plaques.
Hypertension
In summary, it is clear that an elevated blood pressure is associated with both a higher prevalence and incidence of PAD. This is supported by evidence that lower blood pressure is associated with a decrease in the progression rate of PAD and lower blood pressure is associated with less of a decline in the walking ability of patients with intermittent claudication.
In hypertensive subjects, the increased ABI is believed to reflect the arterial stiffness which occurs as a result of medial calcification, an independent predictor of increased cardiovascular morbidity and mortality. An increased ABI is also associated with an increased risk of developing claudication and a faster rate of decline in walking times.
Animal studies suggest hypertensive rats and mice produce higher aortic collagen and lower aortic elastin and increased production of the growth factor transforming enhancer factor in the abdominal aorta. An elevated systolic blood pressure is also associated with a higher resting ABI, approximately 0.02 decrease in ABI for a 10mmHg increase in SBP.
At the microscopic level, a rise in blood pressure causes a shift in smooth muscle cell to a synthetic phenotype, resulting in the production of increased amounts of extracellular matrix and of growth factors. This process progresses to a thickening of the vessel walls and a narrowing of the lumen, the initiation phase of atherosclerosis.
Hypertension is a systemic vascular disease which targets the arterial blood pressure, leading to an increase in the pressure. Historically, hypertension has been linked to the pathogenesis of PAD, protected by the early animal models and the significant beneficial effects of blood pressure lowering therapy on both the natural history of PAD and the high risk of cardiovascular events associated with PAD.
Obesity
Almost 2 million adults and 200,000 children in the United States meet the NIH classification for severe obesity. Obesity is known to be associated with chronic arterial insufficiency in the lower extremities. The Framingham study showed the prevalence of claudication to be 2 to 3 times higher in obese men and women compared to their nonobese counterparts. According to this data, the risk of claudication increases by an estimated 30% for each 10% increase in weight over the desirable range. The risk of claudication at the highest levels of BMI is increased sixfold in men and over 15-fold in women. Obese persons may also present with atypical leg symptoms that are suggestive of arterial insufficiency. Although the prevalence of obesity predicts a potentially large impact on the PAD population, weight reduction and cessation of obesity have not been well examined in this group of patients. This is likely due to concomitant medical problems and atypical leg symptoms that will not prompt testing for PAD. Nonetheless, available evidence suggests that obese individuals suffer a disproportionately higher burden of PAD and have much to gain from successful treatment of this disease.
Blood Pressure Management in Peripheral Arterial Disease
Moderation of alcohol consumption. Although the effects of alcohol on PAD patients are not yet established, it is not advisable for hypertensive patients to increase alcohol consumption due to potential adverse effects on blood pressure and increased cardiotoxic effects from certain medications such as RAS inhibitors. National guidelines recommend that men and women should drink no more than 14 units a week on a regular basis. This may be further modulated if blood pressure control is not achieved.
3.2. Lifestyle modifications Patients with PAD are advised to continue with national guidelines to make healthier choices in their lifestyle that may help lower high blood pressure and thus improve their blood flow. Lifestyle choices are often a more attractive lifestyle change as they require no financial implication or strong persistence compared to taking medications or adherence to frequent monitoring. Weight loss has a significant effect in lowering blood pressure in hypertensive patients. Agetro et al demonstrated that a reduction in 1 kg of body weight resulted in 1 mmHg systolic and diastolic blood pressure reduction, with a 3 kg weight loss reducing blood pressure by 6 mmHg. Obese patients may associate weight loss as a beneficial preventative measure to reduce progression of intermittent claudication to more severe symptomatic disease.
3.1. Medication for blood pressure control Several classes of antihypertensive medications have been shown to be effective in reducing cardiovascular morbidity and mortality, such as renin-angiotensin system (RAS) inhibitors, calcium channel blockers (CCBs), beta blockers, and thiazide diuretics. However, different classes of medications may pose different risks and benefits to patients with PAD. RAS inhibitors, for example, may pose a greater cardiovascular protective effect in PAD patients compared to other antihypertensive agents. In the HOPE trial, ramipril reduced the incidence of cardiovascular death, myocardial infarction, and stroke by 25%. This benefit may be related to the drug’s effect on reducing inflammation, oxidative stress, and preserving endothelial function, which are important pathological processes in PAD progression. Combining RAS inhibitors with a CCB such as amlodipine may be a beneficial antihypertensive regimen for PAD patients, as demonstrated in the ASCOT trial. Compared to a beta-blocker/thiazide diuretic regimen, the RAS inhibitor/CCB regimen reduced cardiovascular events by 14%, as well as a significantly reduced incidence of peripheral arterial disease requiring revascularization. Although these are relatively low Brach scale levels of evidence studies, results may suggest that the combination of specific antihypertensive drugs may be more effective in reducing disease progression in PAD. Ankle brachial pressure index in hypertensive patients with type 2 diabetes.
Hypertension is the most prevalent risk factor for PAD. This patient population has a RR risk of 5.3 for PAD. Treatment of hypertension has been shown to reduce cardiovascular morbidity and mortality, highlighting the importance of hypertension management in PAD. The goal of our review is to describe how to approach blood pressure management tailored to patients with PAD.
Medications for Blood Pressure Control
The most important consideration in the choice of antihypertensive agent is to arrest progression of atherosclerosis and reduce CVD event rates. As discussed previously, patients with PVD have high event rates for myocardial infarction, stroke, and cardiovascular death. Each class of antihypertensive drugs has different efficacy in secondary prevention of these events. Angiotensin converting enzyme (ACE) inhibitors and Angiotensin receptor blockers (ARBs) have been shown to reduce myocardial infarction and stroke rates to a greater degree than other classes of antihypertensive drugs in patients with hypertension and atherosclerosis. High event rates for myocardial infarction and stroke in patients with PVD make ACE inhibitors and ARBs suitable first-line agents. Beta blockers also have been shown to reduce the risk of myocardial infarction and have the advantage of reducing ischemic symptoms in patients with intermittent claudication. Therefore, beta blockers are a suitable first-line agent in PVD patients with coexisting coronary artery disease. Calcium channel blockers are effective antihypertensive agents for patients with PVD, particularly in the elderly. A recent subgroup analysis of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) has shown that in hypertensive patients with PVD, treatment with amlodipine reduces peripheral atherothrombotic events to a greater degree than the beta blocker atenolol. This appears to be due to its greater efficacy in preventing the development of an adverse cardiovascular event.
The antihypertensive agents most frequently prescribed for the control of blood pressure in PVD are the same as those used in the general hypertensive population. A thiazide diuretic will be the drug of first choice in the vast majority of patients because of its proven efficacy in reducing CVD events and low cost. If a thiazide is not tolerated due to the development of worsening claudication or a worsening of peripheral edema, other classes of antihypertensive drugs are suitable alternative drugs depending on comorbidities and the presence of compelling indications for specific classes of drugs.
Lifestyle Modifications
Regular exercise has been shown to improve symptoms of intermittent claudication, increase walking distance, and improve quality of life. Patients should be encouraged to undertake several sessions of supervised exercise per week. At present, the exercise program recommended is 35 minutes of continuous walking to near maximal claudication pain, performed daily or on most days of the week. After this level of exercise can be achieved, duration should be increased to 50 minutes. This level of exercise can be difficult to achieve within a clinic-based program, and home-based exercise is a useful alternative. A recent systematic review has shown that structured home-based exercise programs are effective in improving walking ability. Duration of time spent walking at a pace requiring a moderate level of exertion, considered to be a key factor in improvement of claudication, should be increased. This can be complemented by the advice to reduce time spent sitting. The use of pedometers to record daily step count can be a useful motivational tool. Supervised exercise programs utilize treadmill exercise and/or alternate exercises such as cycling. Upper body exercises can also be utilized, and patients should be encouraged to exercise to the point of claudication pain, at which time exercise should be continued until pain subsides, then stopped and repeated when pain recurs. This so-called “stop-start” exercise has been shown to effectively increase pain-free walking time. In patients with more advanced PAD who suffer severe limiting of walking ability, it should be remembered that upper body exercises and specific exercises improving muscle strength have been shown to improve general fitness and well-being. Those patients with intermittent claudication who have associated cardiovascular risk factors, such as obesity, hypertension, and diabetes, will gain added benefit from initiation of an exercise program in terms of overall improvement of their risk factor profile.
Patients should be encouraged to adopt a healthy lifestyle. Smoking is the most powerful risk factor for PAD, and smoking cessation can increase walking distance, improve the response to exercise training and cilostazol, and generally improve the cardiovascular risk factor profile. Patients need to be educated regarding the etiology of their PAD and the benefits to be gained from altering their behavior. This may involve referral to a nurse-led clinic specializing in cardiovascular risk factor modification.
Importance of Regular Monitoring
Regular blood pressure (BP) monitoring is an essential component of any strategy to control BP. This is particularly important for individuals with PAD, in whom the relationship between BP and clinical events is less clear. In hypertension, studies have shown a clear relationship between the level of BP and adverse cardiovascular events, and for most patients with hypertension, regular monitoring is necessary to adjust the regimen of BP lowering drugs. In contrast, individuals with PAD often have atypical BP responses and may sustain adverse events as a result of postural hypotension following administration of anti-hypertensive drugs, yet there are no data available to guide safe limits of BP in such individuals. More commonly, patients with PAD have co-existing coronary or cerebrovascular disease, and may sustain silent myocardial ischemia or cerebrovascular events when BP is acutely elevated. The role of BP in such events often goes unrecognized and the opportunity to treat or prevent such events by adjusting BP lowering therapy is lost. The best methods for regular BP monitoring in individuals with PAD are unclear. Existing clinical trial data in PAD often provide little information on the methods by which BP was recorded, and in individual clinical encounters a variety of different monitoring methods may be employed. Casual or clinic BP measurement is simple and non-invasive, whereas ambulatory BP monitoring provides a more reproducible assessment of BP load and diurnal variation, and may be a better predictor of adverse events. In well-controlled circumstances, home BP measurement has several advantages for patients, allowing multiple readings to be taken with minimal chance of error from incorrect cuff size or placement, and with good correlation to clinical outcomes. However, little is known of the utility or best methods for BP monitoring in ‘real world’ patients with PAD, and further research is required in this area.
Benefits of Blood Pressure Management in Peripheral Arterial Disease
Management of hypertension in PAD is an important but underappreciated aspect of clinical care. The potential benefits of blood pressure management have been underlined by the recent US guidelines for hypertension management, which recommend lower blood pressure targets in patients both with and without diabetes to reduce cardiovascular outcomes. In the absence of specific studies in patients with PAD, the evidence base for management of hypertension in PAD is drawn from large cohorts and sub-analyses of well-conducted clinical trials looking at cardiovascular events and mortality. The benefits of blood pressure management can be best described by the impact on key clinical outcomes. High blood pressure is the commonest cause of secondary hypertension and is present in up to 80% of patients with PAD. High blood pressure is a powerful independent risk factor for all cardiovascular events and mortality in patients with PAD. Reducing blood pressure in a patient with PAD has been shown to reduce the incidence of cardiovascular events and mortality to the same rate as seen in patients without PAD.
Reduction of Cardiovascular Events
Halting disease progression should reduce adverse cardiovascular events, presumably by prevention of plaque rupture due to stabilization of existing atheroma, a desirable outcome. Data to support this assumption has accumulated. In the Hypertension Optimal Treatment (HOT) trial, although not specifically in PAD patients, reduction of cardiovascular events was highly correlated with achieved blood pressure. In the United Kingdom Prospective Diabetes Study, a 44% reduction in the risk of myocardial infarction was seen in patients treated with any antihypertensive regimen compared to those receiving no specific treatment. This effect was separate from the reduction in event rate attributable to better glucose control. In a similar post hoc analysis of the Heart Outcome Prevention Evaluation (HOPE) study, patients with known PAD (at baseline) derived the greatest reduction in the risk of the combined outcome of myocardial infarction, stroke, or cardiovascular death from treatment with ramipril versus placebo, even though the incidence rate of the same outcome (during the study period) in this subgroup was lower than in any other HOPE subgroup based on different manifestations of disease. Clearly, PAD patients have much to gain if prevention of cardiovascular events through blood pressure management is a plausible objective. Influence of blood pressure upon specific types of cardiovascular events is also an issue. In the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), patients with prior stroke and any degree of cerebrovascular disease accrued significant reduction in risk of recurrent stroke from antihypertensive therapy. Although this event-specific analysis was a post hoc, BP treatment has become fundamental in stroke prevention.
Improved Blood Flow and Oxygen Supply
Accordingly, in the setting of systemic hypertension, an isolated reduction in blood pressure using antihypertensive drugs will result in decreased flow to the affected limb. This is not desirable, but it is likely to be a transient phenomenon and can be prevented by a change to a vasodilatory antihypertensive agent or moderate intake of both types of agent. The overall effect of antihypertensive therapy will vary depending on the profile of the drugs used and the presence of other systemic factors affecting blood pressure. This has been the subject of relatively few studies, but it is clear that the control of hypertension cannot be universally recommended for all patients. A pragmatic approach is by far the most sensible measure as recommended by the blood pressure control subcommittee of the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). This committee concluded that the individualization of treatment was necessary, taking into consideration the coexistence of other diseases and reduction of quality of life in patients.
To understand how the management of systemic hypertension can improve blood flow and oxygen delivery in the affected limb, consider the basic principles of fluid dynamics. Blood pressure is the force that propels blood from the heart and through the arterial tree. Flow (F) is directly proportional to the pressure gradient (ΔP) and the fourth power of the radius (r) of the artery, and inversely proportional to the blood viscosity (η) and the length (L) of the vessel (F = ΔPπr^4/8ηL). Thus, an increase in pressure will translate to increased flow, and vice versa. If the blood pressure is reduced, the flow will decrease. By important laws of conservation, blood flow must remain constant or collateral flow will increase. A decrease in blood flow, however, promotes clotting because stasis is an important stimulus for thrombosis. A decrease in oxygen tension promotes red cell production by the kidneys and erythropoiesis increases blood viscosity which further impairs blood flow. Both effects are an attempt to increase oxygen delivery to tissues but, increased viscosity exacerbates the problem and obviously erythropoiesis is a hazardous compensation in PAD. This will promote ischemia because the deformed arterioles and capillaries cannot dilate in response to reduced oxygen tension or increased metabolism, to maintain tissue oxygen supply. This will result in a spiral of events that will intern exacerbate the ischemia and cause permanent damage to tissues. Increased blood pressure is sensed by the baroreceptors in arteries and reduces sympathetic activity and cardiovascular tone. These are complex reflexes but, essentially a reduction in blood pressure decreases the sympathetic drive and a resultant elevation in sympathetic tone and increased cardiovascular activity will occur with increased peripheral vasoconstriction and decreased arteriolar compliance.
Prevention of Disease Progression
Finally, the effectiveness of blood pressure management at preventing disease progression has significant cost implications for the treatment of PAD. As a chronic disease of elderly individuals, the economic consequences of lower extremity PAD are substantial, and resources expended for the treatment of PAD are projected to rise substantially during the next several decades. If blood pressure management strategies prove to be effective at preventing progression to ischemic symptoms and limb loss, it may lead to substantial reductions in the economic burden of PAD.
Decline in walking ability is a hallmark of PAD, and it has been shown to be the single most important factor leading to a decrease in quality of life among patients with PAD. It is not surprising, therefore, that prevention of decline in walking ability is a primary goal for most patients with PAD. Hypertension has been demonstrated to be an important risk factor for claudication and decline in walking ability among patients with PAD. In a randomized trial of fosinopril, a hypertension management strategy effectively reduced the onset of claudication among patients with PAD compared to placebo. Blood pressure management may also slow the progression of atherosclerosis in the arteries supplying the legs and lead to avoidance of invasive surgical procedures aimed at improving arterial blood supply.
