Current non-HDL cholesterol treatment target insufficiently captures residual cardiovascular risk in very-high risk patients
M K Hansen, K K W Olesen, M B Mortensen, M MaengAbstract
Background
Non-high-density lipoprotein cholesterol (non-HDL-C) is increasingly used as treatment target in patients at very-high cardiovascular risk. The current non-HDL-C target is arbitrarily defined as the low-density lipoprotein cholesterol (LDL-C) target plus 0.8 mmol/L (30 mg/dL) remnant cholesterol (remnant-C). While the target for LDL-C has been modified over the years, the remnant-C amount has remained unchanged. This allows the contribution from remnant-C to increase from one-fifth in low-risk populations with an LDL-C target of 3.0 mmol/L (116 mg/dL) to one-third in very-high risk populations with an LDL-C target of 1.4 mmol/L (55 mg/dL).
Purpose
To examine whether the secondary prevention non-HDL-C treatment target at 2.2 mmol/L sufficiently captures residual risk of atherosclerotic cardiovascular disease (ASCVD).
Methods
Using the population-based Western Denmark Heart Registry, we sampled statin-treated patients with ischemic heart disease (IHD) as determined by coronary angiography (CAG) between 2011-2020. Baseline cholesterol levels were measured within one year after CAG. The contribution from remnant-C was calculated as remnant-C divided by non-HDL-C, expressed in percentages. Patients were stratified according to contribution from remnant-C (<20%, 20-24%, 25-29%, and ≥30%) and followed from 1 year after CAG until the occurrence of ASCVD (the composite of myocardial infarction, ischemic stroke, and cardiovascular death). We used Cox regression models to obtain adjusted hazard ratios (HR).
Results
We included 17,309 statin-treated very-high risk patients with IHD and non-HDL-C ≤2.2 mmol/L. Median age was 67 years and 13,064 (75%) were male. Remnant-C contributed with ≥30% of non-HDL-C in 4,322 (25%) patients. During median 4.5 years of follow-up, 1,507 ASCVD events occurred. The higher the contribution from remnant-C, the higher the risk of ASCVD (Figure 1). Compared to <20% contribution from remnant-C, the adjusted HR of ASCVD were 1.04 (95% CI 0.89-1.21), 1.13 (0.96-1.33), and 1.20 (1.02-1.42) for 20-24%, 25-29%, and ≥30%, respectively. There was a linear relationship between the contribution from remnant-C and the risk of ASCVD with each 10% increment in contribution from remnant-C associated with a 13% higher risk of ASCVD (adjusted HR 1.13, 95% CI 1.05-1.21) (Figure 2).
Conclusions
The current non-HDL-C treatment target of 2.2 mmol/L allows for a substantial contribution from remnant-C in very-high risk patients, which is associated with an increased risk of ASCVD. Therefore, the non-HDL-C treatment target should be redefined to sufficiently capture residual cardiovascular risk in very-high risk patients.