Effect of <scp>PCSK9</scp> inhibitors on remnant cholesterol and lipid residual risk: The <scp>LIPID‐REAL</scp> registry

Cordero, Alberto; Olmo, María Rosa Fernández; Quiroga, Gustavo Aníbal Cortez; Romero-Menor, César; Fácila, Lorenzo; Seijas‐Amigo, José; Murillo, Juan Rondán; Sandín, Miriam; Rodríguez‐Mañero, Moisés; Mora, M C Bello; Valle, Alfonso Salguero del; Fornovi, Aisa; Freixa-Pamias, Román; Bañeras, Jordi; García, Pedro Blanch; Lorenzo, M. Milagros Clemente; Sánchez‐Álvarez, Sergio; López‐Rodríguez, Luis; González-Juanàtey, José Ramón

doi:10.1111/eci.13863

Cited by 10 publications

(4 citation statements)

References 38 publications

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“…Similarly, in the PREDIMED study, in overweight or obese subjects at high cardiovascular risk, TG and RC serum levels, but not LDL-C, were associated with cardiovascular outcomes [44]. Recently, a retrospective registry of real-world patients treated with PCSK9 inhibitors demonstrated a positive effect on RCs and lipid residual risk beyond LDL-C reductions [55].…”

Section: Study Study Population Resultsmentioning

confidence: 96%

Cholesterol Remnants, Triglyceride-Rich Lipoproteins and Cardiovascular Risk

Baratta

Cocomello

Coronati

et al. 2023

IJMS

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Randomized clinical trials with statins and other lipid-lowering drugs have shown the presence of a “residual cardiovascular risk” in those treated to “target” for LDL-cholesterol. This risk is mainly associated to lipid components other than LDL and in particular to remnant cholesterol (RC) and to lipoproteins rich in triglycerides in fasting and non-fasting conditions. During fasting, RCs correspond to the cholesterol content of the VLDL and their partially depleted triglyceride remnant containing apoB-100. Conversely, in non-fasting conditions, RCs include also cholesterol present in chylomicrons containing apoB-48. Therefore, RCs refer to total plasma cholesterol minus HDL-cholesterol and LDL-cholesterol, that is, all the cholesterol present in the VLDL, chylomicrons and in their remnants. A large body of experimental and clinical data suggests a major role of RCs in the development of atherosclerosis. In fact, RCs easily pass the arterial wall and bind to the connective matrix stimulating the progression of smooth muscle cells and the proliferation of resident macrophages. RCs are a causal risk factor for cardiovascular events. Fasting and non-fasting RCs are equivalent for predicting vascular events. Further studies on drugs effect on RC levels and clinical trials to evaluate the efficacy of RC reduction on cardiovascular events are needed.

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Section: Study Study Population Resultsmentioning

confidence: 96%

Cholesterol Remnants, Triglyceride-Rich Lipoproteins and Cardiovascular Risk

Baratta

Cocomello

Coronati

et al. 2023

IJMS

View full text Add to dashboard Cite

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“…More recently, in a post hoc analysis that evaluated data from five randomized controlled trials (RCT), ezetimibe + statins resulted in greater reductions in RC compared to statin monotherapy in both statin-naïve and statin-taking patients [ 34 ]. The multicenter LIPID-REAL registry study, involving 652 patients treated with PCSK9 inhibitors (evolocumab or alirocumab), showed significant reductions in RC (from 29.88 mg/dL to 27.30 mg/dL), TC/HDL ratio, TG/HDL ratio, and the TG-to-glucose index at a median follow-up of 187.5 days, with more pronounced decreases observed in patients whose baseline RC exceeded 30 mg/dL [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

The effect of lipid-lowering therapy on lipid-related residual risk factors: a prospective study

Li,

Gao,

et al. 2024

Lipids Health Dis

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Background Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited. Methods This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment. Results Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45–0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34–0.75; P < 0.001), without a significant increase of adverse reactions. Conclusion Current levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.

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“…Since RC and hsCRP are actively implicated in the formation of atherosclerosis beyond the influence of LDL-C, treatment with RC-lowering and anti-inflammatory drugs for minimizing the risk of cardiovascular diseases has previously been explored. According to recent research, individuals treated with proprotein convertase subtilisin/kexin type 9 inhibitors exhibited benefits with respect to decreased cholesterol remnants and lipid residual risk, beyond the reductions in LDL-C [40]. Specifically, a combined analysis of three randomized controlled trials suggested that alirocumab therapy resulted in a 42.1-52.5% decrease in RC levels compared with placebo [41].…”

Section: Discussionmentioning

confidence: 99%

The residual risk of inflammation and remnant cholesterol in acute coronary syndrome patients on statin treatment undergoing percutaneous coronary intervention

Liao,

Qiu,

et al. 2024

Lipids Health Dis

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Background Residual risk assessment for acute coronary syndrome (ACS) patients after sufficient medical management remains challenging. The usefulness of measuring high-sensitivity C-reactive protein (hsCRP) and remnant cholesterol (RC) in assessing the level of residual inflammation risk (RIR) and residual cholesterol risk (RCR) for risk stratification in these patients needs to be evaluated. Methods Patients admitted for ACS on statin treatment who underwent percutaneous coronary intervention (PCI) between March 2016 and March 2019 were enrolled in the analysis. The included patients were stratified based on the levels of hsCRP and RC during hospitalization. The primary outcome was ischemic events at 12 months, defined as a composite of cardiac death, myocardial infarction, or stroke. The secondary outcomes included 12-month all-cause death and cardiac death. Results Among the 5778 patients, the median hsCRP concentration was 2.60 mg/L and the median RC concentration was 24.98 mg/dL. The RIR was significantly associated with ischemic events (highest hsCRP tertile vs. lowest hsCRP tertile, adjusted hazard ratio [aHR]: 1.52, 95% confidence interval [CI]: 1.01–2.30, P = 0.046), cardiac death (aHR: 1.77, 95% CI:1.02–3.07, P = 0.0418) and all-cause death (aHR: 2.00, 95% CI: 1.24–3.24, P = 0.0048). The RCR was also significantly associated with these outcomes, with corresponding values for the highest tertile of RC were 1.81 (1.21–2.73, P = 0.0043), 2.76 (1.57–4.86, P = 0.0004), and 1.72 (1.09–2.73, P = 0.0208), respectively. The risks of ischemic events (aHR: 2.80, 95% CI: 1.75–4.49, P < 0.0001), cardiac death (aHR: 4.10, 95% CI: 2.18–7.70, P < 0.0001), and all-cause death (aHR: 3.00, 95% CI, 1.73–5.19, P < 0.0001) were significantly greater in patients with both RIR and RCR (highest hsCRP and RC tertile) than in patients with neither RIR nor RCR (lowest hsCRP and RC tertile). Notably, the RIR and RCR was associated with an increased risk of ischemic events especially in patients with adequate low-density lipoprotein cholesterol (LDL-C) control (LDL-C < 70 mg/dl) (Pinteraction=0.04). Furthermore, the RIR and RCR provide more accurate evaluations of risk in addition to the GRACE score in these patients [areas under the curve (AUC) for ischemic events: 0.64 vs. 0.66, P = 0.003]. Conclusion Among ACS patients receiving contemporary statin treatment who underwent PCI, high risks of both residual inflammation and cholesterol, as assessed by hsCRP and RC, were strongly associated with increased risks of ischemic events, cardiac death, and all-cause death.

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Effect of PCSK9 inhibitors on remnant cholesterol and lipid residual risk: The LIPID‐REAL registry

Cited by 10 publications

References 38 publications

Cholesterol Remnants, Triglyceride-Rich Lipoproteins and Cardiovascular Risk

Cholesterol Remnants, Triglyceride-Rich Lipoproteins and Cardiovascular Risk

The effect of lipid-lowering therapy on lipid-related residual risk factors: a prospective study

The residual risk of inflammation and remnant cholesterol in acute coronary syndrome patients on statin treatment undergoing percutaneous coronary intervention

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