Cardiovascular disease (CVD) is still the leading cause of death in Canada. Aggressive management of conventional risk factors makes sense, and surrogate markers are often used as a guide. Last month’s column discussed the shortfalls of blood glucose as an indicator for CV risk in diabetes; this month, we’ll focus on HDL-cholesterol and others.

HDL-C — handle with care

Data from as early as the 1970s shows that preparations boosting HDL-C — such as niacin — are vascular-protective. The “good” cholesterol has clear antioxidant effects, and for every 1% increase in HDL-C, the risk of CV events falls by 1-2%. This discovery prompted novel drug developments; torcetrapib was one of the agents tested. In a large randomized controlled trial with >15,000 patients, the medication was found to raise HDL-C by 72%, while lowering LDL-C by an additional 25%. Unfortunately, total mortality also went up 58%. Off-target effects of torcetrapib included a rise in systolic BP of 5.4 mm Hg and activation of the renin-angiotensin-aldosterone system, leading to increased aldosterone production with a fall of potassium and a rise in serum sodium. The drug has now been abandoned, but newer niacin agents are being tested.

There’s a recent trend to use micro-albuminuria and proteinuria as markers for atherosclerosis in both diabetic and non-diabetic populations. The more protein or albumin found in a patient’s urine, the higher the CV event rate. This realization was followed by a series of small, short-term trials that demonstrated benefit of combining angiotensin converting enzyme (ACE) inhibitor and angiotensin-II receptor blocker (ARB) therapy in patients at risk for nephropathy and vascular disease. Many physicians have since combined these two classes of medications to reduce both proteinuria and micro-albuminuria.

But the recent ON TARGET trial, involving >25,000 patients, showed that the drug combo increased the risk of hyperkalemia and renal dysfunction. Subgroup analysis may shed light on open questions, but for now, giving an ACE along with an ARB isn’t recommended outside of advanced congestive heart failure.

Indicators such as C-reactive protein, lipoprotein-A, homocysteine and other markers of inflammation all have potential for the assessment of atherosclerosis risk. In select patients, these new markers may indeed help guide therapy. For the vast majority, however, my first recommendation is still to start by targeting conventional risk factors, i.e. LDL-cholesterol, weight disorders, blood pressure and smoking. Simple steps such as adding more fruits and vegetables to the diet and exercising regularly can go a long way.