Coronary atherosclerotic lesions in human immunodeficiency virus-infected patients: a histopathologic study

Abstract

Background: Studies suggest human immunodeficiency virus-positive (HIV+) patients have an increased risk of coronary artery disease (CAD), yet little is known about the histopathology, severity, or distribution of lesions.

Methods: The coronary arteries of 66 deceased AIDS patients and 19 HIV controls (age <55) were dissected and graded for percent luminal stenosis by intimal lesions, percent of intima involved with lipid, and extent of intimal calcification on a scale of 0 to 3. Medical histories, antiretroviral therapies, and CAD risk factors were reviewed.

Results: HIV+ patients were older than controls (P=.06), and more were male (P=.02). Thirty-five percent of HIV+ patients had stenosis >or=75% of at least one artery. Compared to controls, HIV+ patients had three times greater odds of stenosis >or=75%, controlling for age and sex (one-sided P=.03). Older age and male sex were also risk factors (one-sided P<.001). HIV seropositivity was associated with increased plaque lipid content (one-sided P=.02) and calcification (one-sided P=.08). Duration of HIV infection, antiretroviral therapy, and immune status did not predict severe disease in multivariate analyses. Previously unreported patterns of dystrophic calcification were observed in HIV+ patients and older controls.

Conclusions: Young to middle-aged patients dying from advanced AIDS have atherosclerotic CAD that may result in luminal narrowing, heavy calcification, and high plaque lipid content. The pattern of disease, location of lesions, and plaque composition are typical of atherosclerosis in HIV-negative patients. No relationship between antiretroviral therapies and atherosclerosis was seen in this small study of heavily treated patients.

Fig 1:

Definitions: A) Fibromuscular intimal hyperplasia from a case of transplant coronary artery disease showing a normal media (M) with overlying concentric intimal thickening (I) causing complete luminal occlusion. Some inflammatory cells are also present; B) Atherosclerotic plaque defined as an eccentric lesion with a lipid core (LC) covered by a fibrous cap (FC) (asterisks indicate shoulder region of the plaque). The region opposite the eccentric plaque exhibits normal histology; C) Section of artery with adaptive intimal thickening also showing a normal media (M) with mild, non-occlusive intimal thickening (I); and D) Higher magnification of C showing intima composed of smooth muscle cells and collagen (all H&E, A, B, and C orig mag 12.5x, D orig mag 200x).

Figure 2:

Quantification of calcification: A) Grade 1 calcification only seen at high magnification (arrows); B) Grade 2 calcification seen as small blue dots at low magnification (arrow); and C) Grade 3 calcification seen as prominent confluent blue regions at low magnification (all H&E, A orig mag 400x, B and C orig mag 12.5x)

Figure 3:

A) Complicated atherosclerotic plaque with plaque rupture (arrow). Note mural thrombus and plaque hemorrhage in region of plaque rupture; B) Atherosclerotic plaque with moderate, ≥50% luminal narrowing; and C) Atherosclerotic plaque with severe, ≥75% luminal narrowing (all H&E, A orig mag 20x, B and C orig mag 12.5x).

Figure 4:

Percent of all patients with moderate atherosclerotic disease: ≥50% vessel narrowing

Figure 5:

Percent of all patients with significant atherosclerotic disease: ≥75% vessel narrowing