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COLUMNS
Asia needs to wake up to the threat of peripheral artery disease
The incidence of PAD is rising four times faster in Asia than Europe, if left untreated, PAD can lead to strokes, heart attacks, lower limb amputations complications caused by restricted blood flow and clots.

While most Asians are aware of the dangers of coronary artery disease (CAD) far fewer are aware of Peripheral Artery Disease (PAD) and the risks it poses. PAD, like CAD is a form of atherosclerosis, a disease in which plaque builds up in the arteries. Left untreated it can lead to strokes, heart attacks, lower limb amputations and a host of other complications caused by restricted blood flow and clots.

A recent study reported the incidence rate of PAD is on the rise across the world, but it is rising four times faster in Asia than Europe. Globally it increased by 17.02 percent between 2010 and 2015. But while Europe saw the rate rise by less than 5 percent, in Asia it rose by nearly 20 percent and across the Western Pacific it rose by more than 22 percent. More than 70 percent of the world’s new PAD cases over that period, and the years since, have occurred in the Asia-Pacific region.1

In South East Asia in particular, PAD is occurring in a younger demographic. PAD is most common in the age group 55-64 in the Americas, and in Europe it affects an even older demographic at 65-74, but in South East Asia the age group most affected is younger; 45 to 54 years.1

The World Health Organisation (WHO) warns the incidence rates for PAD are set to continue to grow as Asia’s population ages and the rates of diabetes skyrocket.2 There is some good news though, PAD can be treated with heart-healthy lifestyle changes, medicines, and as a last resort catheter procedures or surgeries.

We spoke to Professor Tan Huay Cheem, Director, National University Heart Centre, Singapore (NUHCS), Professor, Yong Loo Lin School of Medicine, National University of Singapore to learn more about PAD, its risk factors, treatments and how to avoid it:

1. What is peripheral artery disease (PAD)?

PAD is the third most common clinical manifestation of atherosclerosis after coronary artery disease (CAD) and stroke but it receives much less research attention and there is much less awareness and understanding of the disease among the general public. It is a major cardiovascular disease characterised by debilitating atherosclerotic occlusion (blockage) of peripheral (away from the heart) arteries, most commonly in the lower extremities. It can also affect the arms, neck and abdomen. The disease can be asymptomatic or accompanied by symptoms, such as intermittent claudication (cramping), atypical leg pain, critical limb ischaemia (reduced blood flow to the extremities caused by severe obstruction of the arteries), and occasionally acute limb ischaemia (a sudden lack of blood flow to a limb caused by embolism or thrombosis). Both symptomatic and asymptomatic PAD are associated with a significantly increased risk of cardiovascular morbidity and mortality.

2. What are the causes and risk factors of PAD?

Risk factors that contribute are similar to those for CAD, they are diabetes, ageing, smoking, obesity, high blood pressure, high cholesterol, family history of heart disease, and excess levels of C-reactive protein or homocysteine. In Asia the most significant risk factor and probably the one contributing most to the increases in the incidence rate of PAD across Asia is diabetes.

3. Who is most at risk of developing PAD?

Diabetics with poorly controlled blood glucose levels, patients with a history of coronary heart disease (high cholesterol, hypertension ), smokers, patients with kidney failure, and the elderly are most at risk of developing PAD. As with all forms of atherosclerosis, the risk of developing PAD increases as we age with men prone to developing it in their 50s or 60s and women a decade or so later. The more risk factors you have the higher your personal risk.

PAD can and does affect both sexes. It was once thought of, like CAD, as something that mainly affected middle-aged men; probably because men with PAD are more likely to also have CAD, and often their PAD was diagnosed when they were being treated for CAD; or perhaps men just complain more about leg pains. There are several reasons why women may not have their PAD diagnosed early. They tend to develop the disease a decade or so later in life than men, in their 60s or 70s, by which time they may also have other conditions causing leg pain or numbness such as arthritis or peripheral neuropathy (nerve damage). Consequently, women are often not diagnosed until the disease is more severe.

4. PAD is on the rise across the world but in some regions, including Asia, it is rising faster than others; what factors create those differences?

There are usually a variety of contributing factors when we observe an increasing incidence of a disease and the significance of any individual factor may vary from region to region or country to country.

For instance, the causes of the increase in PAD in some of Asia’s high-income countries (HICs) with well-developed healthcare systems, such as Japan and Singapore are likely to different from those in low- and middle-income countries (LMICs) like Indonesia and the Philippines. Probably the single biggest factor in Japan will be their rapidly ageing population. Our rapidly ageing population plays a role in Singapore as well, but we also have a big problem with diabetes. The other two countries have two of the youngest populations in Asia so the risk factors there will be different. In Indonesia smoking is much more prevalent; 76 percent of men smoke there compared to 28 percent in Singapore.3 In the Philippines the driver might be increased numbers of obese people and the subsequent rise in diabetes rates; according to the Food and Nutrition Research Institute (FNRI) of the Department of Science and Technology, the percentage of the population that is obese has doubled in 30 years and the prevalence of obesity in the country is now 31.1 percent.4

A recent study found that PAD was on the rise not just in Asia but also in LMICs in Africa and the authors suggested that socioeconomic inequality should be added to the list of risk factors for PAD.1

5. PAD seems to be occurring in a younger demographic across South East Asia than in some other regions like Europe and the Americas, how does Singapore compare?

In Singapore, although we are seeing an increase in PAD among younger people below 50 — linked to the rise in diabetes — our ageing population also plays a significant part. The over 80 age group is the fastest growing demographic in Singapore having almost doubled in number over the past decade.5

6. Are there symptoms people should look out for?

Many people with PAD have mild or no symptoms, especially in the early stages. Some people have claudication, pain or cramping in their limbs, most commonly the lower leg when walking and climbing stairs. The pain usually disappears after a few minutes’ rest. In advanced PAD pain may occur even when sitting or lying down, this is called ischaemic rest pain.

The severity of claudication varies widely, from mild discomfort to debilitating pain. Severe claudication can make physical activity difficult but exercise such as walking is recommended for the long-term management of the condition. The location of the pain depends on the location of the clogged or narrowed artery. Pain and cramps in the calf are the most common.

Other symptoms and signs of PAD include:

  1. Painful cramping in either one or both hips, thighs, or calf muscles after certain activities.
  2. Numbness or weakness in the legs
  3. The affected leg or foot often feels cold, especially when compared with the opposite foot
  4. Sores on the toes, feet or legs that don't heal properly/ completely
  5. The foot or lower leg turning blue or purple
  6. Losing hair or slower hair growth on the feet and lower legs
  7. Slower toenail growth
  8. Patches of shiny skin on the legs
  9. No pulse or a weak pulse in the lower legs or feet
  10. Erectile dysfunction in men

7. How is PAD diagnosed?

The doctor will usually start with a physical examination, they will palpate the foot and feel for an arterial pulse and check for other physical indicators such as coldness or colour changes. This is followed by an ankle-brachial pressure index (ABPI) or ankle-brachial index (ABI) test to measure the ratio of the blood pressure at the ankle to the blood pressure in the upper arm (brachium). If the blood pressure in the leg is significantly lower than the arm it could indicate blocked arteries PAD. If there is lower BP in the leg a duplex ultrasound maybe used to locate any narrowed or blocked arteries. Blood tests looking for signs of diabetes, kidney disease and high cholesterol may also be performed.

If the ABI and ultrasound tests have detected an abnormality that requires further clarification for diagnostic purposes, or to guide the best treatment options, conducting a computerized tomography (CT) or magnetic resonance imaging (MRI) scan may be required. If these reveal a significant abnormality an invasive, catheter angiogram may be recommended. An angiogram involves injecting contrast dye into the affected arteries and taking X-ray images to see where blockages are located. If blockages are detected, the doctor may then opt for some form of catheter procedure to open up the vessel and improve blood flow. These procedures are similar to those used on the heart.

8. How is PAD treated and managed?

PAD is a form of atherosclerosis, so a diagnosis of PAD indicates patients are at higher risk for heart attack and stroke, not just leg pains and mobility problems. Therefore, the primary treatment objective is to prevent stroke and heart attack. The treatment and management of PAD is multifaceted, and the attending physician will tailor a regimen to individual patients taking into consideration their overall cardiovascular health, any comorbidities, current medication, age, and lifestyle.

The first step in managing your PAD will usually be lifestyle changes, also intended to improve your general cardiovascular health. Smoking cessation, a healthy diet, weight loss and more exercise are all typically recommended. Ironically for a disease which often first presents as pain when walking, doing more walking is highly recommended.

The second step is assessing and managing any comorbidities to reduce their potential impact on the PAD. PAD is often associated with CAD, diabetes, high blood pressure and elevated cholesterol and other age-related chronic conditions. In general, the older the patient the more likely there are to be multiple comorbidities.

The third step is medication. This will be tailored to the patient depending on comorbidities and any current medication. The main purpose of medication is to reduce the risk of heart attack and stroke and prevent complications. If suitable some patients may receive medication to reduce the symptoms of claudication and improve mobility and overall quality of life.

Antiplatelet drugs which stop blood cells called platelets from sticking together and forming harmful clots are prescribed to reduce the risk of stroke and heart attack. Aspirin and clopidogrel are the most commonly prescribed antiplatelets. Some patients may receive an antiplatelet drug and a vasodilator which widens blood vessels in the legs and can help to reduce claudication.

Patients with concomitant conditions such as high blood pressure or high cholesterol or some form of cardiovascular disease (CVD) may also be prescribed anti-hypertensive or statin medications to manage those conditions and these drugs can also benefit the PAD.

In the last couple of years, the use of novel oral anticoagulants (NOACs) for treating CAD and PAD has become more popular in the USA and Europe; the low dose rivaroxaban with aspirin regimen that came to prominence after the publication of the COMPASS study. However, the adoption rate of the regimen for CAD and PAD patients in Singapore is still quite low.

When it comes to the wider adoption of the rivaroxaban plus aspirin therapy, it not so much a matter of cost or the acceptance of the evidence, it is that doctors are not sure which groups in the CAD and PAD populations would most benefit from it. Personally, I would say it is only suitable for patients with high-risk, symptomatic CAD and PAD, until we see more research to identify for which other specific groups within the broader CAD and PAD populations the benefits would outweigh the risk.

For advanced PAD that is limiting mobility and causing severe pain some form of endovascular or surgical procedure, the same sorts that are used for heart disease, may be needed.

Endovascular means, “inside the blood vessel.” Endovascular surgeries are minimally invasive procedures that involve inserting thin tubes called catheters into a blood vessel to repair it. A variety of devices, including cameras and stents can be introduced to the blood vessel via the catheter.

The most common procedure is a balloon angioplasty. It involves temporarily inserting and inflating a tiny balloon where your artery is clogged to help widen the artery. Angioplasty is sometimes combined, although less often for PAD than CAD, with the permanent placement of a small wire mesh tube called a stent to help prop the artery open and decrease its chance of narrowing again.

Occasionally an atherectomy might be performed instead of angioplasty. It also uses a catheter but this time with a laser or tiny blade on the end that removes the plaque from the walls of the artery as it moves past the blockage. The catheter collects the plaque as it is shaved away. When the catheter is removed, the shaved plaque is removed from the patient's body restoring blood flow through the artery.

The most severe PAD may require bypass surgery. This is very similar to heart bypass; it involves a surgeon taking a section of the patient’s healthy vein, or a synthetic replacement, and using it to create a bypass around the blocked section of the leg artery.

9. What are some of the latest advances in the management of PAD?

Although it is the third most common clinical manifestation of atherosclerosis, in the past PAD has been the focus of much less research than coronary artery disease and stroke. However, that is beginning to change and there have been some promising developments in recent years.

There have been some promising developments in recent years.

On the technology side, better techniques combined with smaller wires and low-profile balloon stents have now made it possible to treat even the smallest blocked arteries below the knee and in the foot. This is especially relevant in diabetics as these smaller below knee and foot arteries are the ones usually affected in PAD. Another advancement in technology is the use of better angiography imaging to better locate and evaluate the arterial lesions as well as evaluate the blood flow in the foot before and after intervention (perfusion imaging). We also use less contrast per procedure which is much better for patients. One of the risks of excess contrast use is the development of acute kidney failure, especially in diabetic patients.

Another promising technology is lithoplasty balloon catheters which use shockwave energy bursts to crack the surface of the plaque, this is particularly useful for harder plaques with large amounts of calcium in them. This makes the blood vessel easier to inflate with a balloon and also allows for better absorption of any drug applied to the cracked surface of the plaque.6

Lithotripsy has been used for many years to break up stones in the kidney, bladder and ureter and the technology has now been miniaturised to use in angioplasty catheters. The technology is promising but as always, more research is needed.

References

  1. The Lancet, “Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis” Vol 7 August 2019. Retrieved from: https://www.thelancet.com/action/showPdf?pii=S2214-109X%2819%2930255-4
  2. The World Health Organisation, “CVD Fact-Sheet” 17 May 2017. Retrieved from: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
  3. DATAleads. Asia’s smoking addiction. Retrieved from: http://annx.asianews.network/content/asia%E2%80%99s-smoking-addiction-54868
  4. BusinessMirror Editorial, Bearing the heavy burden of obesity, 22 May 2019. Retrieved from: https://businessmirror.com.ph/2019/05/22/bearing-the-heavy-burden-of-obesity/
  5. Population in Brief 2019, Over 80, (n.d) Retrieved from: https://www.strategygroup.gov.sg/files/media-centre/publications/population-in-brief-2019.pdf
  6. D. Fornel. New Technologies to Treat Peripheral Artery Disease (PAD). Diagnostic and Interventional Cardiology, FEBRUARY 22, 2016. Retrieved from: https://www.dicardiology.com/article/new-technologies-treat-peripheral-artery-disease-pad

About the interviewee

Professor Tan Huay Cheem
Director, National University Heart Centre, Singapore

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