Mt. Sinai Medical Center, New York City

(from Volume 6, Issue 1, 1998)

The cardiovascular manifestations of PXE are due to the abnormal calcification of elastic tissue found in the walls of blood vessels and heart valves. While skin lesions are considered to be the clinical marker of the disease, the cardiovascular manifestations of PXE are frequently present and are not related to the severity or presence of skin lesions in PXE patients. Because the involvement of the cardiovascular system may be the only manifestation of the disease, which potentially can lead to serious complications, it is important for the physician and the patient to be able to identify them. The purpose of our article is to highlight the major cardiovascular manifestations of PXE.

Claudication (Leg Pain)

Intermittent claudication or leg pain on walking is the most common cardiovascular manifestation in PXE patients. The calcification of peripheral arteries in the legs that results in the reduction of blood flow contributes to the leg pain experienced by PXE patients. It is estimated that up to 30% of PXE patients experience leg pain, usually in the calf. There is no gender difference in the frequency of the claudication. Peripheral arterial calcification can result in weak peripheral pulses which can be felt during routine physical examination. Also x-rays of the legs can occasionally show the calcification of the arteries. One treatment recommended for intermittent claudication is the medication pentoxifylline (Trental) which relieves the symptom by increasing the blood flow to the leg arteries. The usual dosage of Trental for adult patients in controlled-release tablet form is a 400 mg tablet three times a day with meals. The relief of the symptom can be seen within 2-4 weeks.

Mitral Valve Prolapse

The association of PXE and mitral valve prolapse has been cited in medical literature, but the prevalence of this problem among PXE patients has not been well established. Lebwohl et al conducted a study that was published in the New England Journal of Medicine where they performed echocardiography in PXE patients to determine the prevalence of mitral valve prolapse. The found that 70% of the PXE patients in their group have mitral valve prolapse diagnosed by echocardiogram, a noninvasive procedure commonly performed by cardiologists. Although the frequency of this heart valve disease increases with age in the general population, the youngest patients in Lebwohl’s study constitute half of the patients diagnosed with mitral valve prolapse. Thus, it is important for patients with PXE, regardless of age, to undergo mitral valve prolapse work-up since this heart valve abnormality may warrant treatment with prophylactic anitobiotics prior to procedures such as dental work. The medical work-up can be done by simple auscultation of the heart where a characteristic murmur can be heard and also by echocardiography which is considered to be a more sensitive and specific test.

Coronary Artery Disease

One of the most serious cardiovascular manifestations in PXE is coronary artery disease that can result in premature myocardial infarction or heart attack in these patients who otherwise may have no risk factors for heart disease. The underlying pathology is the calcification of the elastic layer of the coronary arteries. This form of accelerated cardiovascular disease can resemble common atherosclerosis in the general population. Thus, it can be difficult to distinguish the PXE-associated form from the more common atherosclerosis associated with aging or other hereditary diseases, especially in the absence of the typical skin lesions. It is important to determine the coronary artery status in PXE patients. If a diagnosis of PXE has been established, then it is important to determine the patient’s coronary artery status for further appropriate treatment. History, physical examination, routine cardiograms and stress test, if indicated, are helpful. Even without skin lesions, if a young patient has accelerated cardiovascular disease without any other risk factors, a diagnosis of PXE should be considered. The coronary arterial bypass surgery using the patient’s own arterial graft, which can be calcified in PXE patients, should be done with caution in these patients. The artery can be examined at the time of surgery to see if it is calcified before it is used for bypass.

Hypertension

Hypertension has been reported in PXE patients and despite the evidence of vascular calcification in these patients, it is not as common as expected. Studies have reported ranges of 8% to 24% and the prevalence increases with age. Many studies have shown that the underlying etiology of hypertension in PXE patients is due to abnormal calcification of the renal arterial system. However, the true pathogenesis is yet to be determined. Because of the existing fragility of the blood vessels, it is especially important for PXE patients with hypertension to have good control of their blood pressure.

Gastric Hemorrhage

GI tract bleeding in PXE is a relatively common occurrence, especially among the younger patients and also in pregnant women. The frequency of this manifestation has been estimated to be as high as 13% in PXE patients and has been observed in pediatric patients under 10 years of age. The stomach is the most common site of GI tract bleeding. The underlying pathology is, again, the calcification of elastic tissue in the gastric arteries which contribute to the fragility of the vessels. Often the bleeding is not severe and can stop spontaneously so the problem can go undetected. Nonetheless, severe gastric hemorrhage does occur and usually requires immediate surgical intervention. Despite the rare possibility of severe bleeding in pregnant patients, it is still important for PXE patients to be aware of this risk. The obstetrician who is following the pregnant patient should occasionally perform stool examinations for blood.

Summary

PXE patients should be aware of the different cardiovascular manifestations that can associate with this disease. Preventive measures such as avoidance of smoking, control of blood pressure, and control of diabetes are helpful. Aerobic exercise under the instructions of a physician and a heartwise low cholesterol diet are also suggested.