Impact of Peripheral Arterial Disease on other diseases

October 2, 2019

Peripheral Arterial Disease (PAD) has many symptoms, some more specific than others, but is most often entirely asymptomatic, much to the exasperation of physicians, who only discover this insidious disease when it is already in an advanced stage. This is a most grave fact, both from the perspective of PAD itself and associated complications, and that of other comorbid diseases.

Despite affecting at least two hundred million individuals worldwide (estimate of about 202 million patients for 2010), PAD is often undiagnosed or diagnosed far later than it should be, complicating effective treatment and management [1]. One of the reasons is the fairly high prevalence of the asymptomatic form of the disease: about 40% of patients are entirely asymptomatic, about half of them have symptoms that could be attributed to other medical conditions and only 10% have PAD-typical symptoms [2, 3].

The other reason is lack of awareness in the general population and also amongst some physicians – this holds true even for developed, high-income countries [4, 5, 6, 7]. Additionally, many physicians are unfamiliar with modern diagnostic tools, based on measuring Ankle-Brachial Index (ABI) that would enable them quick and easy diagnosis without any special procedures or additional training [8]. Change cannot come too soon as PAD is especially detrimental if patients have other diseases (highly likely).

How does PAD affect the course of other diseases?

On its own, PAD is associated with significant mortality and disability rates: patients are at a notably higher risk of mortality in general with estimates of 5-year mortality rate going as high as 30% (versus 10% for control group without PAD) [9]. However, it is also comorbid with many other medical conditions, particularly those of cardiovascular nature, and usually worsens morbidity, disability and mortality associated with them – to varying degrees.

A good example would be coronary artery disease (CAD), the leading cause of mortality worldwide, by itself and amongst cardiovascular diseases (CVDs) [10]. Studies have shown that those patients who have both CAD and PAD (up to 42% of patients) fare worse in terms of cardiovascular health and mortality than those with either [11, 12, 13, 14]. The same can be said for its association with ischaemic stroke.

Some patients who have survived a stroke also have PAD, more specifically, about 41% of them have other arterial diseases (about 30% have CAD, 5% PAD and the rest have both diseases) [15]. Studies have also shown that event rates for stroke, myocardial infarction and death (due to cardiovascular causes) were higher for individuals with stroke or/and transient ischaemic attacks (TIA) and PAD than for patients with the same cerebrovascular condition(s) and CAD [16]. What is more, 21% of patients with stroke (and TIA) and symptomatic PAD had a vascular event or required hospitalisation, while those with stroke (TIA) and without symptomatic PAD had the same outcome in only 13% of cases [17].

However, it should be noted that the aforementioned statistic paints an incomplete picture as it included only symptomatic manifestations of PAD [18]. Additional studies unveiled a far grimmer situation: 51% of patients in the SCALA (Systemic Risk Score Evaluation in Ischaemic Stroke Patients) and 33.5% in PATHOS (Polyvascular ATHerothrombosis Observational Study) studies had a low ABI score (indication of possible PAD), but only 10% had symptoms typical for PAD [19, 20], yet another reason for preventive screening (especially of those in risk groups) for PAD on the basis of the ABI score.

Amongst other medical conditions that are significantly impacted (in a negative way of course) by comorbid PAD is diabetes (both type 1 and 2). Diabetes itself or should we say complications associated with it was responsible for 1.6 million deaths in 2016 and that number is unlikely to change for the better in the near future as prevalence rates of diabetes are steadily rising [21].

At least 20% of diabetics have (symptomatic) PAD, but this number is generally recognised as being an underestimate since many times PAD is entirely asymptomatic, hindering timely diagnosis (in the absence of modern diagnostic tools) [22]. It is estimated that intermittent claudication, the most typical symptom of PAD, is 3.5 times more prevalent in male and 8.6 more prevalent in female diabetics than in non-diabetics [23]. However, intermittent claudication is the least problematic symptom/complication of PAD for diabetic patients.

Far more worrisome is the prevalence of concomitant PAD and diabetes in individuals with critical limb ischaemia (CLI), an advanced stage of PAD associated with significantly heightened risk of amputation and subsequent mortality: about 50% of patients with CLI are also diabetics [24]. Studies likewise revealed that the severity of CLI is worse in diabetics [25]. On the topic of amputations: diabetics are at 15 to 20 times greater risk of amputation that non-diabetics [26].

Another disease affected by the presence of PAD is chronic obstructive pulmonary disease (COPD). While information about associated mortality is sound and well researched – about 3.2 million individuals died due to the disease in the year 2015 – the data connected with prevalence of PAD in COPD patients is sparse and limited to that obtained in small single-centre studies [27]. Estimates therefore vary from 8% to 37% [28, 29]. Studies also indicated that patients with COPD are at twice the risk for developing PAD and that those with both have significantly higher mortality rates [30, 31].

Physicians who have patients with PAD should be cognisant about its deleterious effects on other comorbid medical conditions the patient might also have. The same recommendation is applicable to specialists, like cardiologists and diabetologists (endocrinologists), who should screen their patients for possible PAD on the basis of the ABI score.