Prof Thomas Marwick

Patient management guided by their coronary artery calcium (CAC) score appears to improve preventive efforts and reduce cardiovascular risk in individuals with a family history of premature coronary artery disease.

However whether that translates into reduced coronary plaque burden has yet to be shown.

The Australian Coronary Artery calcium score: Use to Guide management of Hereditary Coronary Artery Disease (CAUGHT-CAD) trial comprised 450 patients with intermediate range CAC scores (1-400).

All were provided with guideline-directed cardiovascular risk advice regarding modifiable risk factors of diet, exercise and smoking cessation where required.

Patients and their physicians in the usual care group remained blinded to the CAC score and therefore any lipid lowering therapy introduced or modified was not informed by CAC.

Patients and their physicians randomised to CAC guided management were instead advised of the CAC and patients commenced on atorvastatin 40 mg daily. Patients were also encouraged to display their CAC image somewhere as a daily reminder.

At the 12-month follow-up, the study found CAC-guided statin therapy was associated with an 18% relative risk reduction in the primary outcome of 10-year cardiovascular risk.

The CAC-guided group had significant reductions in total cholesterol (1.52 mmol/L) and LDL (1.39 mmol/L) compared to baseline while no changes were observed in the usual care group.

“Analysis of baseline and 12-month systolic blood pressure showed 2.2 mmHg (− 4.47 to 0.04, p = 0.05) reduction in average blood pressure at 12 months in the CAC-guided compared to control group, driven by a reduction of 5.8 mmHg (− 10.5 to − 1.05, p < 0.03) in those on antihypertensive therapy,” the study said.

It said reductions in blood pressure contributed 14% of the absolute risk improvement in the CAC-guided treatment arm.

The study, published in Atherosclerosis, found CAC assessment was not associated with improved adherence to self-reported low salt diet, heart healthy diet according to Australian dietary guidelines, or 5% weight reduction.

Differences in smoking rates and alcohol use were not significant between treatment groups.

The study said the reductions in total cholesterol and LDL were independent of commencing or continuing statins.

“While statin-induced reduction in LDL-C level was the main contributor of pooled cohort equation (PCE) risk reduction, our results illustrate an independent effect from CAC scoring in reducing cardiovascular risk factors beyond lipid lowering therapy,” the investigators said.

Patients in the usual care group who were prescribed statins typically received an average dose-equivalent of atorvastatin 20 mg.

“This may represent under-treatment, as those with a family history of premature coronary artery disease have worse outcomes than the general community at any level of CAC, and the benefit from statin therapy is likely to be net positive in those with CAC scores ≥100.”

“Moreover, our cohort all had established plaque and only 43% of our participants achieved LDL-C levels <1.8 mmol/L, a potential threshold associated with plaque regression.”

Changing clinician behaviour

The study investigators, including Professors Stephen Nicholls, Tony Stanton, Gerald Watts and Thomas Marwick, said the findings highlight the limitations of current CVD prevention advice.

“Our findings are consistent with the evidence that standard CVD risk prediction tools do not clearly increase the use of primary prevention interventions, improve risk factor profile and may not deliver clinically meaningful reductions in cardiovascular outcomes.”

They said the CAC scores may actually influence physicians more than the patients.

“Improvement in systolic blood pressure was most evident in those already on anti-hypertensive therapy, suggesting both up-titration and compliance with therapy may have improved with knowledge of subclinical disease.”

“This is consistent with current hypertension guidelines which suggest blood pressure targets should be assessed in the context of baseline risk, and the presence of subclinical disease and positive family history may personalise the management plan and reinforce the benefits of up-titrating therapy.”

“Nonetheless, the results also highlight the preponderant role of statins in primary prevention – the magnitude of risk reduction from LDL-C lowering therapy was primary responsible for risk difference between treatment groups, with improvements in blood pressure accounting for ≤15% of the total risk difference between treatment groups,” they concluded.

Professor Marwick, from the Baker Heart and Diabetes Institute, told the limbic that plaque volume measurements from the study were yet to be reported.

“Our previous papers (eg. in MJA last year, and a cost-effectiveness analysis in JACC-Imaging) … support the use of CAC, but the imaging results will be the most important.”

He said they hoped that the final results from the study support a policy change to reimbursement of CAC scoring.