NEW ORLEANS, LA—Low endothelial shear stress (ESS) independently predicts progressive lumen obstruction in a low-risk Japanese population. Areas of low ESS showed increased local plaque thickness and excessive expansive remodeling over 6- to 10-month follow-up and were associated with increased need for PCI by 12 months.

Findings of the PREDICTION trial were presented by Peter H. Stone, MD, of Brigham and Women’s Hospital (Boston, MA) on April 5, 2011, at the American College of Cardiology Scientific Session/i2 Summit.

ESS is “the tangential force derived from the friction of blood flowing across the endothelium,” Dr. Stone reported. Where laminar flow is disturbed downstream from an obstruction, there is in vivo and ex vivo evidence that local low ESS leads to increased low-density lipoprotein build-up, intense inflammation with accumulation of activated macrophages, increased plaque growth, plaque cap thinning, and excessive expansive remodeling. On the other hand, local moderate or high ESS is vasculoprotective.

Way to Predict Progression

PREDICTION sought to characterize the natural history of CAD by focusing on the consequences of low ESS in 506 ACS patients after their index event. All subjects had CAD and at least 1 coronary artery requiring PCI as well as another artery not planned for PCI that was suitable for IVUS investigation.

After completion of PCI, patients underwent 3-vessel vascular profiling with IVUS and bi-plane coronary angiography. The researchers generated 3-D reconstruction of the lumen, external elastic membrane, and plaque and calculated velocity vectors and shear stress patterns, resulting in an ESS “profile” of each arterial segment assessed. Routine follow-up vascular profiling was done at 6 to 10 months in a subset of 329 patients. Clinical follow-up was obtained through 12 months.

Low ESS at baseline, most often seen in the 1 or 2 segments distal to an obstruction, was significantly associated with percent change in maximum plaque thickness at follow-up (P = 0.009). Arterial segments with low or moderate ESS were more likely than those with high ESS to exhibit excessive expansive remodeling.

On multivariate analysis, low baseline shear stress and maximum plaque thickness greater than 1 mm at baseline were significant predictors of worsening lumen narrowing (table 1).

Table 1. Baseline Predictors of Worsening Lumen Narrowing

Baseline plaque burden greater than 60% and low ESS were also both significant predictors of worsening luminal obstruction requiring PCI at follow-up (table 2).

Table 2. Baseline Predictors of Worsening Luminal Obstruction Requiring PCI

Major adverse cardiac events were rare in this low-risk population. Progressive lumen obstruction in a de novo lesion that required PCI was seen in 10% of patients on follow-up imaging.

“These observations may justify the development of a large-scale clinical intervention trial to identify early stages of a high-risk coronary lesion and then randomize patients and their lesions to preemptive local intervention versus usual care,” said Dr. Stone. 

'Monumental' Effort to Study Shear Stress

“This is a monumental study,” said session co-chair Patrick W. Serruys, MD, PhD, of Erasmus University (Rotterdam, the Netherlands) during a discussion of the trial. “I thought it would be impossible to conduct a study on shear stress, but here it’s been done.”

Dr. Stone commented, “I think that one thing that we’ve learned over the years is the remarkable dynamic nature of vascular pathology and the vasculature’s endogenous response to atherosclerosis that forms.” Many times the vasculature’s compensatory mechanisms will kick in to reduce the risk of developing atherosclerosis in an area of low shear stress, he added.

“Our hypothesis is that the areas of particularly low shear stress, very low, are those areas that seem to take on a life of their own,” Dr. Stone explained. “Because of the intense inflammation that develops in these areas, there is excessive expansive remodeling which perpetuates the adverse low shear stress environment and that is what perpetuates the process, culminating in these vulnerable plaques that rupture.”

He went on to say that the goal of treatment would be to “recreate normal physiologic flow that does not perturb the endothelial cell. That would be the most effective and rational approach to induce quiescence in those vascular territories.”  

Further analyses will look at differences in shear stress among diabetics and other subgroups as well as characterize the shear stress dynamics downstream from stented segments.

Source:

Stone PH. The PREDICTION Trial: In-vivo assessment of coronary endothelial shear stress, arterial remodeling, and plaque morphology to predict coronary atherosclerosis progression and rupture in man. Presented at: American College of Cardiology Annual Scientific Session/i2 Summit; April 5, 2011; New Orleans, LA.