Lipoprotein(a) in progressive coronary artery disease: beyond classical cardiovascular risk parameters
Authors: Sangha J , Edroos S , Glancy J , Prasad N 
Published: October 2022

Abstract

Introduction
Classical primary preventive cardiovascular disease (CVD) risk algorithms, such as the Framingham risk score and the widely used QRISK score in the UK, predate large-scale deep-phenotyped biomedical research resources. There is therefore the opportunity to identify novel predictors. In addition, whilst CVD risk profiling is well studied in the context of primary prevention, there is a paucity of data examining risk in regard to secondary prevention.

Purpose
To identify independent predictors of repeat coronary artery revascularisation, following index coronary angioplasty.

Methods
The UK Biobank is a large prospective multicentre study which recruited over 500,000 participants in the UK aged 37–73 years at entry between 2006–2010. Data are derived from an array of physical measurements, self-reported measures and biological samples, together with longitudinal linkage to hospital inpatient records and death registries. Procedural codes were used to identify patients who had undergone first coronary angioplasty from 2006 onwards. Repeat revascularisation (RR) was defined as angioplasty or bypass grafting occurring at least 9 months after the index angioplasty, in order to preclude instances of staged revascularisation and in-stent restenosis. Data were censored at January 2021 or date of death as appropriate.

Results
A total of 12,853 participants underwent a first coronary angioplasty during the study period, with 1,394 (10.8%) requiring RR over a median follow-up of 6.5 years. The average age was 64 years in the RR cohort and 1117 (80%) were male. Univariate analyses confirmed a number of established associations with RR, including for example diabetes mellitus and hypertension. Median lipoprotein(a) concentrations were 27.6 vs. 30.3nmol/L in the RR group, p=0.066. Cox regression analyses (n=7,216) incorporating 21 biometric and clinical parameters demonstrated that lipoprotein(a) &gt;80nmol/L was one of six independent predictors of time to RR (HR 1.24, p=0.006), independent of other lipids. The strength and significance of this association persisted when the number of covariates was reduced to include only other lipids and classical cardiovascular risk parameters. LDL, HDL, and triglyceride levels were not significant predictors in this model.

Conclusions
Lipoprotein(a) is identified as a major independent driver of RR. However current European Society of Cardiology guidance does not recommend measurement of Lipoprotein(a) in the context of progressive coronary artery disease. Furthermore, it is known that strategies such as lifestyle advice and statins – recommended in all patients with established coronary artery disease - do no reduce lipoprotein(a), whilst niacin and PCSK9 inhibitors do have a significant effect. Indications for lipoprotein(a) measurement must therefore be broadened, so that specific treatments to lower it can be instituted in order to reduce the burden of progressive coronary artery disease.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Herefordshire Heart Fund