Thoracic and abdominal aorticatherosclerosis

Roger S. Blumenthal, MD, is director, Ciccarone Center for the Prevention of Heart Disease

,
associate professor of medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland, an

Cardiology Review® Online, February 2006, Volume 23, Issue 2

It was not until Virchow identified the cellular contributions to thrombosis that physicians began to visualize arteries as dynamic tissues.

It was not until Virchow identified the cellular contributions to thrombosis that physicians began to visualize arteries as dynamic tissues. We are just beginning to appreciate the key components of atherogenesis and why atherosclerosis preferentially affects certain arterial beds. Over the years, several imaging methods have emerged that capture different phases of the formation of atherosclerotic plaques.

The current study by Momiyama and colleagues compared the effects of 5 mg versus 20 mg of atorvastatin (Lipitor) on thoracic and abdominal aortic plaque size, as measured by magnetic resonance imaging (MRI) in 40 asymptomatic patients with hypercholesterolemia.1 The purpose was to determine whether MRI could capture subtle differences in plaque burden and morphology in patients using 2 different doses of atorvastatin. A review of autopsy studies shows a correlation between atherosclerotic plaque burden in the thoracic aorta and coronary arteries.2 Thoracic atherosclerosis has thus been shown to be a stronger predictor of cardiovascular events than traditional risk factors.3

Patients excluded from the study were those currently taking atorvastatin; however, patients taking other HMG-CoA reductase inhibitors (statins) were enrolled following a 4- to 8-week washout period. This included 7 patients (37%) in the 20-mg group and 9 patients (43%) in the 5-mg group. En­rolling these patients may have blunted the effects observed on plaque burden and morphology. The degree of plaque regression tended to be greater in patients without a history of statin use.

The study patients had a low-density lipo­protein (LDL) cholesterol level > 150 mg/dL. Based on current clinical guidelines, patients at intermediate risk (10-year risk > 10% according to the Framingham Risk Score) should be started on drug therapy if the LDL cholesterol level is >= 160 mg/dL after therapeutic lifestyle changes fail to achieve a goal LDL cholesterol level of 130 mg/dL.4 Thus, the population studied is a close representation of the population that would be started on statin therapy. The doses chosen are based on the maximal approved dose in Japan. Certainly, for secondary prevention, the results from 2 pivotal trials, the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study and the Pra­vastatin or Atorvastatin Evaluation and In­fection Therapy (PROVE-IT) trial, suggest that higher doses achieve greater clinical outcomes.5,6 It is possible that higher doses may have translated to further plaque regression.

Compared with baseline measurements, the reductions in LDL cholesterol level were 47% and 34% in the 20-mg and 5-mg groups, respectively. This is in keeping with earlier studies showing similar LDL cholesterol reductions within this dose range.4 There were no statistically significant differences in plaque size between the 2 groups at baseline. After 12 months of statin therapy, the 20-mg group had a reduction in maximal vessel wall thickness (VWT) of 12% and vessel wall area (VWA) of 18% in the thoracic aortic plaques, whereas the 5-mg group did not (0% change in VWT and a 4% increase in VWA).

Interestingly, both groups failed to show a reduction in either VWT or VWA in abdominal aortic plaques. The 5-mg group actually showed an increase of 5% in VWT and 12% in VWA. A similar progression was not observed in the 20-mg group, suggesting that this dose halted progression. Calcification was noted in 15% of the abdominal aortic plaques and 10% of the thoracic aortic plaques. This difference was not statistically significant. Only 1 thoracic plaque was identified as containing a lipid-rich core, with a hypointense region on T2-weighted MRI at baseline. This lipid-rich plaque appeared to regress on repeated imaging at 12 months.

The authors’ analysis indicated a correlation between plaque regression and percent reduction in high-sensitivity C-reactive protein (hsCRP; r = 0.49). A better correlation, however, was noted with reduction of LDL cholesterol levels (r = 0.64), suggesting that percent LDL cholesterol reduction contributed most to plaque regression. This differs from the findings in the REVERSAL study, which showed a greater correlation between hsCRP and atheroma volume.5

The authors found that thoracic and abdominal aortas responded differently to atherosclerotic progression and regression. Arterial specimens from the Pathobiological Deter­min­ants of Atherosclerosis in Youth (PDAY) study showed fatty streaks and raised lesions localized to the dorsal region of the infrarenal abdominal aorta, which preceded atheromatous in­volvement of the thoracic aorta.7 This study also suggested that atheroma formation in the aorta may precede coronary atheroma formation.

A study by Jaffer and colleagues showed similar plaque distributions in adults.8 Using MRI, they evaluated subclinical aortic atherosclerosis in the offspring cohort from the Framingham Heart Study. Aortic atherosclerosis was present in 41% of men and 38% of women. Plaque burden increased with age and usually occurred in the abdominal aorta compared with the thoracic aorta.

Hydrodynamics appear to be the driving force behind atherogenesis. Atherosclerotic plaques tend to occur in proximal segments immediately following branch points. Whether it is the actual flow disturbance that occurs at branch points or the lack of laminar flow that contributes to atherogenesis remains controversial. Although endothelial cells are thought to arise from a common precursor, smooth muscle cells in various arteries have distinct embryonic origins, which may help account for some of the observed differences.9

Additionally, certain arterial vessels develop intimal “cushions,” or regions of intimal expansion consisting of smooth muscle cells and extracellular matrix. These cushions, which may be prone to the development of atherosclerosis, have been found in the proximal left anterior descending ar­tery and the carotid siphon.10,11

Although this study does not ap­pear to uncover new findings, it does confirm findings from previous studies.5,12 Using MRI, Corti and colleagues evaluated the effects of simvastatin (Zocor) on plaques affecting the thoracic aorta and carotid arteries in patients with documented atherosclerosis.12 At 12 months, statistically significant reductions in VWA and maximal VWT were observed in both the carotid and aortic plaques. The au­thors concluded that a minimum of 12 months was required to detect plaque regression by MRI, despite evidence of lipid lowering at 6 weeks.

These studies suggest that the earliest signs of plaque regression shown on MRI are decreased VWA and VWT, which can be seen at 12 months; however, a longer treatment interval of 18 months may be required to show an increase in lumen area. These subtle changes, which can be captured by MRI, appear to be dose-dependent. In addition, this study highlights regional differences in the predisposition to atherosclerosis between the thoracic and abdominal aortas.

The clinical application of such technology beyond academic investigation remains to be defined. A screening tool to identify patients at risk for cardiovascular events during the asymptomatic period that permits monitoring of response to therapy is necessary to provide reliable primary and secondary prevention. MRI provides the ability to characterize, quantify, and longitudinally assess atherosclerotic plaque burden without ex­posing patients to invasive procedures or ionizing radiation.