L14 - Lipids (Lecture #1 Part B)

What is cardiac catheterization?

A procedure in which an intravascular catheter is inserted into the heart/blood vessels to evaluate cardiovascular function and structure.

What can cardiac catheterization measure or evaluate?

1) Pressures in the atria and ventricles, 2) cardiac output (CO), 3) vascular resistance, and 4) cardiovascular structural features using radiopaque contrast.

What is coronary angiography?

An imaging procedure in which radiopaque contrast is injected into the coronary arteries during catheterization so the coronary vessels can be visualized and areas of stenosis/occlusion can be identified.

How does coronary angiography help evaluate coronary artery disease (CAD)?

Contrast outlines the coronary artery lumen, allowing visualization of the location and severity of coronary artery stenosis or occlusion.

What is the difference between cardiac catheterization and coronary angiography?

Cardiac catheterization involves placing a catheter into the cardiovascular system to measure pressures, CO, resistance, and/or evaluate structures; coronary angiography specifically uses contrast through a catheter to visualize the coronary arteries and identify stenosis.

Who performed the first cardiac catheterization?

Werner Forssmann performed the first cardiac catheterization on himself in 1929.

Who pioneered selective coronary angiography?

Mason Sones, Jr.; his work led to the development of coronary angiography for visualization of coronary arteries.

What is coronary artery bypass grafting (CABG)?

A surgical revascularization procedure that creates an alternate route for blood to flow around a blocked or severely narrowed coronary artery.

What is the main strategy of CABG?

Bypass the blockage so blood can reach myocardium downstream from the obstructed coronary artery.

Who is considered the father of CABG?

René Favaloro of the Cleveland Clinic.

What is balloon angioplasty?

A catheter-based procedure in which a balloon is positioned within a stenotic coronary artery and inflated to widen the narrowed lumen and restore blood flow.

How does balloon angioplasty improve coronary blood flow?

Inflating the balloon compresses/displaces the atherosclerotic plaque and expands the narrowed arterial lumen, improving blood flow.

What is percutaneous myocardial intervention (PMI)?

A catheter-based revascularization procedure used to reopen a stenosed or occluded coronary artery, typically using balloon angioplasty followed by placement of a coronary stent.

What is the purpose of a coronary stent during PMI?

The stent acts as a scaffold that keeps the coronary artery open after the stenotic lesion has been expanded.

What happens during coronary catheterization and stenting?

Contrast angiography identifies the coronary occlusion → a catheter is advanced to the lesion → balloon angioplasty opens the narrowed vessel → a stent is placed to maintain vessel patency → blood flow improves.

How do CABG and PMI differ?

CABG surgically creates a new route around a coronary blockage, whereas PMI uses a catheter to reopen the existing coronary artery with balloon angioplasty and usually a stent.

Who pioneered balloon angioplasty?

Andreas Gruentzig, who later worked at Emory University.

What are the major approaches covered for treating coronary atherosclerotic disease?

Revascularization with CABG or PMI and pharmacologic reduction of atherosclerotic cardiovascular risk with lipid-lowering drugs such as statins and PCSK9 inhibitors.

What is the rate-limiting step in cholesterol synthesis?

Conversion of HMG-CoA to mevalonate by HMG-CoA reductase.

What is the mechanism of action of statins?

Statins competitively inhibit HMG-CoA reductase → ↓ hepatic cholesterol synthesis → ↓ intracellular hepatic cholesterol → ↑ hepatic LDL receptor expression → ↑ removal of LDL from the blood → ↓ plasma LDL-C.

Why does inhibiting HMG-CoA reductase lower circulating LDL?

Reduced hepatic cholesterol causes hepatocytes to increase LDL receptor expression, increasing uptake and clearance of circulating LDL particles.

What is the major cardiovascular benefit of statins?

They lower LDL-C and reduce atherosclerotic cardiovascular risk.

Who discovered the first statin?

Akira Endo; mevastatin was an early HMG-CoA reductase inhibitor.

What is PCSK9?

A protein that binds hepatic LDL receptors and promotes their degradation, decreasing the number of LDL receptors available to remove LDL from the circulation.

What normally happens when PCSK9 binds an LDL receptor?

The LDL receptor is targeted for lysosomal degradation rather than recycled back to the hepatocyte surface → fewer LDL receptors → less LDL clearance → higher circulating LDL-C.

What is the mechanism of action of PCSK9 inhibitors?

PCSK9 inhibitors prevent PCSK9 from promoting LDL receptor degradation → more LDL receptors are recycled/available on hepatocytes → ↑ LDL uptake from blood → marked ↓ LDL-C.

How do statins and PCSK9 inhibitors both ultimately lower LDL-C?

Both increase the ability of the liver to clear circulating LDL through LDL receptors: statins increase LDL receptor expression by reducing hepatic cholesterol synthesis, while PCSK9 inhibitors prevent LDL receptor degradation.

What is evolocumab?

A PCSK9 inhibitor that lowers LDL-C by preventing PCSK9-mediated degradation of hepatic LDL receptors.

What was the GLAGOV trial?

A trial evaluating evolocumab in patients with angiographic evidence of CAD who were already receiving chronic statin therapy, using intravascular ultrasound to assess coronary atherosclerotic plaque.

What did the GLAGOV trial demonstrate about evolocumab?

Adding evolocumab to chronic statin therapy produced a greater improvement in percent atheroma volume and increased the proportion of patients experiencing plaque regression.

What did the GLAGOV trial suggest about cardiovascular events?

Major adverse cardiac events were numerically reduced with evolocumab, but the trial was not powered to establish differences in clinical cardiovascular outcomes.

What is the key connection between statins, PCSK9 inhibitors, and atherosclerosis?

Both therapies markedly reduce LDL-C, targeting a major driver of atherosclerosis; intensive LDL lowering can reduce cardiovascular risk and may promote regression of coronary atherosclerotic plaque.