Cardiovascular disease: treating the disease, not the risk factors

Thursday, 18 Aug 2022

As part of the Amgen Cardiovascular Academy – International Webinar Series in July 2022, Professor Stephen Nicholls, Program Director, Victorian Heart Hospital, hosted a discussion on cardiovascular disease (CVD) and personalised risk assessment with Professor Christie Ballantyne, Chair of Cardiovascular Medicine at Baylor College of Medicine in Houston, Texas, and panellist Professor David Colquhoun, Cardiologist, Wesley Medical Centre, Queensland.

Risk assessment is a critical first step in CVD prevention, which traditionally involves looking at risk markers. Inflammatory biomarkers can be used to assist with the assessment for global CV risk and identify suitability for certain interventions. High-sensitivity C-reactive protein (hs-CRP) is a well-known inflammatory biomarker measured in practice. However, Mendelian randomisation studies do not support a causal relationship between hs-CRP and risk of coronary artery disease.1 Prof. Ballantyne explained, “If you can find something that is both a risk marker and in the causal pathway, it is logical that this may not only identify the risk, but also be a target of therapy.” To this end, interleukin-6 (IL-6) signalling has been identified as a potential causal biomarker1 and there are ongoing studies, which Prof. Ballantyne described as,  “Targeting IL-6 specifically in a high-risk population with chronic kidney disease and elevated hs-CRP.”

The relevance of biomarkers and metabolomics in CV risk assessments

Currently, there is advanced lipid testing and inflammatory and cardiac biomarkers available in clinical practice. Metabolomics allows for assessment of a panel of metabolites; however, the markers tend to have “relatively modest hazard ratios,” according to Prof. Ballantyne. He noted that metabolomics is could therefore be useful “for identification of metabolic pathways that are important for the disease that we might be treating.” At present, the data from metabolomic studies do not impact clinical practice much in terms of risk identification, he explained. There is also ongoing research with newer technologies (e.g., aptamer arrays), including an assessment of 5,000 patients, which was used to derive a 27-protein model to predict CV events and showed improvement in c-statistics versus a clinical model (0.71 [0.69–0.72] versus 0.62 [0.60–0.63]).2 “This area is fraught with complexities…[but] it may be a great tool to understand pathways and potential targets,” noted Prof. Ballantyne.

Genetics as a way forward in preventative risk assessment

The biggest problem in cardiovascular disease is we do too little too late,” said Prof. Ballantyne. In the HeartCare study, a panel of genes associated with CVD was developed and polygenic risk score, variants in the LPA gene encoding lipoprotein (a) and specific pharmacogenomic variants were evaluated.3 Findings showed 9% of the patients had high impact Mendelian mutations in key risk genes. In the clinician survey results (n=13), 60% agreed the HeartCare study results improved overall clinical care of the patient beyond usual care, and 84.4% reported medical management change based on HeartCare results for a given patient.3 With regard to genetics, Prof. Ballantyne suggested that taking a preventive approach to CVD involves testing for familial hypercholesterolaemia (FH) and lipoprotein (a) combined with assessing polygenic risk scores and rare pathogenic variants.

Imaging in personalised risk assessment

There is variability amongst imaging techniques in terms of quantitative and reproducible data. Prof. Ballantyne noted issues with carotid intima-media thickness (CIMT) measurements include poor reproducibility of results and lack of quantitative information in relation to plaque. On the other hand, he described coronary artery calcium (CAC) score as: “A tool that is very easy to use clinically and the reproducibility is high from location to location. There is a good correlation between the amount of calcium detected and overall plaque burden.” Prof. Ballantyne emphasised the clinical utility of CAC scores: “Identification of who is likely to have an event, compared to traditional risk factors…and individualisation of therapy.” In terms of secondary prevention, he noted, “as a general rule, the intensity of therapy is determined by the risk of the patient.” Patients with higher burden of atherosclerosis and/or activity of atherosclerosis, show the greatest benefit from proprotein convertase subtilisin/kexin type 9 (PSCK9) inhibition.

In summary, Prof. Ballantyne noted, “What is already making an impact for the present is imaging in terms of personalisation that really makes a big impact for your patients.” Another imaging modality that is growing rapidly is computer tomography (CT), which will likely “continue to make the biggest short-term impact,” he said.

Prof. Nicholls concluded with a reflection on how far risk prevention has come since 1973: ”Here we are in 2022, where we do a lot better. But we’ve still got a long way to go. As Prof. Ballantyne said, “Let’s prevent the fire from happening in the first place.”

Join the next CV Academy International Webinar Series Heart Failure: Professor Carolyn Lam from the National Heart Centre, Singapore on 15 September 7.30 to 8.30 pm.  To register click here


This article was commissioned by Amgen Australia Pty Ltd. The content is based on studies and the presenter’s opinion. The views expressed do not necessarily reflect the views of the sponsor. Before prescribing please review the full product information of relevant products via the TGA website. Treatment decisions based on these data are the responsibility of the prescribing physician.


  1. Khera AV et al. Nat Rev Genet 2017;18(6):331–344.
  2. Williams SA et al. Sci Transi Med 2022;In press.
  3. Murdock DR et al. Genet Med 2021;23:2404-2414.



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