Interventional Cardiovascular Therapy (AICT) joint meeting 2009， Dr. Roberto Ferrari presented some of his research regarding advanced coronary artery disease (CAD) management.  Of the numerous recent advances this field has seen in recent years related to interventional therapies， imaging， diagnostics， and in pharmacology， Dr. Ferrari gave provided us with a summary and review of clinical studies and specific pharmacological research in animal models for advanced CAD management.

    As we all know too well， cardiovascular disease (CVD) continues to be the leading cause of death in the developed world， with a coronary event occurring every 26 seconds among Europeans and resulting in approximately one death per minute.  Longitudinally， cardiologic interventions have increased survival associated with cardiac events 7-10 years according to some studies.  However， among cardiovascular diseases CAD is still the greatest cause of death while efforts to diminish its pervasiveness have proven problematic.  Inspiring the direction of Dr. Ferrari’s personal research are the early parts of the CVD continuum， particularly pre-disease risk factors as well as endothelial events associated with disease development.

    Citing results of multiple clinical trials of more than 50K patients including HOPE， PEACE， QUIET， and EUROPA， of with Dr. Ferrari was chairman， analysis of ACE-inhibitor effect on disease progression shows that not all improve prognosis.  Among those that did confer protection， Perindopril proved so efficacious the HOPE Trial reached an early endpoint.  However， the mechanism of ACE-inhibitor mediated cardiovascular protection is less clear.  Obviously the lowering of blood pressure as a leading risk factor for CVD development is a possibility but does not account for the disparity in improved prognosis among commonly used agents.  Dr. Ferrari and his team hypothesized that ACE inhibitors like Perindopril may provide endothelial protection and therefore curb early disease development.  The endothelium does indeed play a large role in CAD development， comprising and area of more than 800 m2， producing more than 250 active substances， and going through a continuous renewal with programmed cell death about every three months.  When apoptotic rates exceed those of endothelial regeneration the early loss of vessel continuity initiates the biochemical sequence of atherosclerosis.

    In the Pertinent sub-study it was shown that CAD patients do indeed have higher rates of endothelial apoptosis， which decreases significantly with Perindopril therapy compared to placebo controls.  Among the ACE inhibitors studied (Trandolapril， Enalapril， Ramipril， and Perindopril) Perindopril and Ramipril resulted in increases in angiotensin II and decreases in highly pro-inflammatory TNF-冄億  In a rat study conducted by Dr. Ferrari， 8 mg doses of Perindopril significantly lowered TNF-冄 levels after just one week of therapy.  Furthermore， flow cytometric analysis showed significant increases in circulating endothelial progenitor cells from the bone marrow upon Perindopril activation.  This and other evidence in human populations suggests that Perindopril may provide better protection than hypertension control for CAD by protecting the myocardium as well as endothelial cells.

    Two retrospective studies of the CASS Registry and INVEST Trial also showed correlations between heart rates (HR) and mortality associated with CAD.  The two studies found that HR greater than 73 or 75 beats per minute (bpm)， respectively， were linked with more coronary events in patients already diagnoses with CAD.  In his own Beautiful Trial， Dr. Ferrari investigated whether HR could be another predictor of later events.  He found that CAD patients with HR greater than 70 bpm had more hospitalizations， revascularization procedures， and myocardial infarctions than those whose pulses were lower than 70 bpm.  In a small randomized study involving the If -channel blocker Ivabradine (b-blockers not chosen due to extracardial action)， which act directly on sino-atrial node tissue to delay calcium channel mediated nodal depolarization and low the HR， Dr. Ferrari confirmed the earlier retrospective study results with treatment being linked with fewer CAD events.  According to Dr. Ferrari， even a small reduction of 7 beats/min/day is significant and can have real results keeping patients healthier longer.