Many patients schedule a visit to the Kahn Center (office or virtual) because they have learned they inherited a cholesterol molecule called Lipoprotein(a) or Lp(a). This particle, Lp(a), is found in 20-25% of people and can promote damage to blood vessels and the aortic valve leading to heart attacks, strokes, need for stents and bypass, and even the need for valve surgery. We specialize at the Kahn Center in managing these patients.
Lp(a) is a large lipoprotein similar to LDL, but the structure contains apolipoprotein(a) linked to apolipoprotein B-100. Largely genetically determined, Lp(a) has been shown to be an independent predictor of ASCVD risk and calcific aortic stenosis. Several genetic studies have shown a causal relationship between high levels of Lp(a) and cardiovascular disease and there are multiple therapies in development to treat and lower it.
The more commonly known cholesterol particle, LDL-cholesterol or LDL-c, can be easily controlled with lifestyle and medications. Unfortunately, Lp(a) is not so easy to control. A new study looks at whether a high Lp(a) in the blood is still a risk if the LDL-c is lowered with medications like statins. The study reported Lp(a) in mg/dl, an older unit, and most labs now use nmol/L, about 2.5 times higher.
A meta-analysis of 27,658 participants enrolled in 6 placebo-controlled statin trials was performed to assess the association of LDL-C and Lp(a) levels with risk of fatal or nonfatal coronary heart disease events, stroke, or any coronary or carotid revascularization (ASCVD).
The multivariable-adjusted association between baseline Lp(a) level and ASCVD risk was modeled continuously using generalized additive models, and the association between baseline LDL-C level and ASCVD risk by baseline Lp(a) level by Cox proportional hazards models with random effects.
Compared with an Lp(a) level of 5 mg/dL, increasing levels of Lp(a) were associated with ASCVD risk in statin- and placebo-treated patients.
Among statin-treated individuals, those with Lp(a) level >50 mg/dL (≈125 nmol/L) had increased risk across all quartiles of achieved LDL-C level and absolute change in LDL-C level.
Even among those with the lowest levels of achieved LDL-C level, those with Lp(a) level >50 mg/dL had greater ASCVD risk (38% higher than those with Lp(a) level ≤50 mg/dL).
The greatest risk was observed with both Lp(a) level >50 mg/dL and LDL-C level in the highest group.
Conclusions: These findings demonstrate the independent and additive nature of Lp(a) and LDL-C levels for ASCVD risk, and that LDL-C lowering does not fully offset Lp(a)-mediated risk. New drugs are in development to lower Lp(a) but for now, treatment is a challenge.
On of the senior authors, Dr. Sam Tsimikas of UCSD, said You can control LDL cholesterol-mediated risk and you'll have a benefit, but at each level of LDL, you'll have a higher risk if your Lp(a) is elevated. In other words, you won't get all the benefit you might get from a statin if your Lp(a) is elevated. Historically, the thought was that if you control LDL, you don't need to worry about Lp(a),” said Tsimikas. “A lot of clinicians grew up believing that for the last two decades. “The implication is you have to treat both. You can't now say: treat the LDL and don't worry about your Lp(a). You have to treat LDL for the LDL-mediated risk, but you have to address the Lp(a)-mediated risk as an independent variable.
We have enrolled patients in 3 ongoing studies of new therapies for Lp(a). It is hoped that by the end of 2025, we will have the first agent, pelicarsen, from Novartis Pharmaceuticals. The drug is injectable and will likely be limited to persons with prior heart attack, stent, or bypass surgery.
