Atherosclerotic plaque morphology and Therapeutic strategies – Medical and Endovascular.
A lecture by Prof. Pinjala R K, Dept of Vascular surgery, NIMS in ISVIR 7th Annual meeting at Mumbai, J W Marriot Hotel, on 1st Nov 2008.




Atherosclerosis of the arteries slowly progress over a period of time with small fatty streaks to complicated plaques with calcification, thrombosis or hemorrhage. In the past surgeons used to bypass the diseased segments and stayed away from the lesions so, there was probably they have felt there was limited need for understanding the morphology of these lesions but with the endovascular recanalization the interest in better understanding was rekindled among the specialists. So, we would certainly like to look at the role of different types of therapies based on the morphology of plaques to get good results with cost effectiveness.
In the recent past many new terms are used quite often by the specialists such as – Unstable plaque, plaque erosion, plaque ulceration, athero-thrombosis, intra plaque hemorrhage and heterogenous plaque. All these terms indicate that the plaque is not only causing problems due to its size (obstructive nature) but also due to the intrinsic morphology of the plaque. Necrotic lipid core (>40% of plaque content), Inflammatory cell component and thinning of the fibrous cap of plaque are three important changes associated with the unstable plaques. In given segment of atherosclerotic artery there can be distribution of stable and unstable plaques in different patterns. Suspicion, detection and imaging of the vulnerable plaques adequately is the challenge we have to pass to look at the therapeutic strategies.
Imaging of the unstable plaque or vulnerable plaque is important to understand morphology and plan the therapies. Biomarkers can only give us indirect evidence of the load of unstable plaques in a person. People with diabetes are known to have more number of vulnerable plaques in given than the non diabetic persons. The internal regulatory mechanism tries to suppress these vulnerable plaque complications to some extent for some time. Angioscopy was used in the early 80s but the images were not clear and it was cumbersome to do the (invasive) angioscopy in routine clinical practice. Intravascular ultrasound (IVUS), Optical coherence tomography are the other imaging modalities used to detect the lesions. Plaque Thermography detects the temperature differences and helps in pointing out the vulnerable plaques with slightly increased temperature. Non invasive methods are duplex scan (gray scale gradients), CT scan, MRI and PET scan were used to study the morphology of the plaques. These investigations are expensive in today’s practice and they are investigational tools for the research studies. The unstable plaque morphology has been found to be changed to stable plaque morphology by the medical therapies, at the same time preventive measures such as protection devices (thrombus retrievers) were used during the endovascular interventions.
The cumulative survival of an individual is found to be affected by the size of plaque (degree of stenosis) and morphology (heterogenous /homogenous plaques or no plaques) independently. The larger plaques (with greater stenosis) are found to be more heterogenous and obviously it indicates that have a more complex plaque morphology which has progressed over a long period of time. The PET scans could detect the (hot spots) inflamed plaques (macrophage infiltration) and they disappeared with medical therapies and corresponded with the benefits shown by the drugs such as statins.
Medical therapies are needed much before the patients arrive for the interventions of obstructive lesions. Some times it reminds me that the peptic ulcer disease presents as pyloric stenosis if it persists for long time after incomplete treated or untreated for a very long time. We then consider a gastro-jejunostomy to bypass the pyloric stenosis. Of course, some performed pyloroplasty and re-stenosis was the known complication in such patients that required re-surgeries when adequate suitable medical treatments were not available. There is some similarity here between plaque ulceration and peptic ulceration. Today we know that peptic ulcerations are linked with helicobacter pylori and adequate therapies are needed to eradicate the local infection of the gastric mucosa to cure peptic ulcer disease and at the same time prevent the re-infection. When this understanding was not there we known that some patients were subjected to major surgeries such partial gastrectomy or total gastrectomy.
The atherosclerotic plaque progression from stage 1 to advanced stages may not be incremental. Type 2 or 3 plaque may become type 5 or 6 suddenly in a person and result in sudden occlusion of vascular lumen without giving enough to develop the collaterals. So, the plaque disease needs early attention and preventive measures to make them less and less vulnerable to avoid the sudden transition of the plaques to the advanced stages.
Correction of endothelial dysfunction with statins and ACE inhibitors, correction of the prothrombotic state with antiplatelet drugs, improvement of endothelial functions by dietary regulations and exercise, diabetes control, hypertension control will benefit the patients to improve the survival, reduce the complications and improve the results of interventions or reduce the need for them in the beginning or later re-interventions. Medical management of plaques is as important as the ascertaining the luminal patency with the interventional measures.
Atherosclerosis plaque distribution in the coronary, carotid, peripheral vascular circulations is also dependent to some extent on the genetic component. Neovasculogenesis of the plaque, role of the growth factors and role of stem cells in healing of the ulcerated plaque is under investigation. The recently popularized drug eluting stents have given a new window to understand the drug delivery at the site of ulcerated plaques which can modify the plaque morphology. Probably in future we may be able to deliver drugs to early lesions through (magnetized tips) micro-catheters directed by Spiral CT (Fast) imaging guidance. Probably we may be also looking at different class of anti-inflammatory drugs which are specially designed for the vascular inflammation as it seems to be different from the other types of aseptic chronic inflammations.
In future management of vascular (occlusive) disease aims at treating the plaques before they develop complex morphology with complications/ stenosis. Similarly in the post Endovascular intervention phase strict measures will be taken to change the morphology of the neighboring the plaques and prevent their progression to maintain the results.

Prof. Pinjala R K’08