Colchicine reduces biomarkers of myocardial injury after non-CABG surgery

10th February 2023

Low dose colchicine before and following non-CABG cardiac surgery is associated with a reduction in biomarkers of myocardial cell injury

A study by Chinese researchers has shown that using colchicine for two days before and five days after, non-post-coronary artery bypass grafting (non-CABG) cardiac surgery, significantly lowers markers of myocardial injury and inflammation.

It has become recognised for many years that in cardiac surgery involving cardiopulmonary bypass, there is a systemic inflammatory response that leads to both organ injury and post-operative morbidity. While colchicine is often been used in the management of gout, the drug also has anti-inflammatory effects and can have a positive impact on several rheumatic diseases with a potential benefit in cardiac disease. Cardiac surgery is known to elevate markers of myocardial injury such as troponin levels and one study suggested that if post-operative values exceed ≥ 0.8 μg/L on the first post-operative day, a further 10% increase is significantly associated with all-cause, 12-month mortality and other adverse events. With some data showing that a perioperative course of colchicine, in patients undergoing standard coronary artery bypass grafting, reduced post-operative surgery-related myocardial damage, in the current study, the Chinese team wondered if this myocardial protective effect would extend to non-CAGB cardiac procedures.

Turning to patients undergoing other types of cardiac surgery such as mitral and aortic valve replacement, atrial septal defect repair and atrial myxoma resection, the researchers randomised patients, 1:1 to receive colchicine 0.5mg daily or placebo for three days before and five days after their cardiac surgery. The primary outcome was the level of cardiac troponin T (cTnT) 48 hours after surgery whereas secondary outcomes included biomarkers of myocardial injury including creatine kinase-MB (CK-MB) and procalcitonin (PCT).

Colchicine and myocardial injury

A total of 121 patients with a mean age of 59.4 years (57.8% male) were included and of whom, 59 were given colchicine.

At the 48-hour post-operative timepoint, patients assigned to colchicine had significantly lower cTnT (p < 0.001), CK-MB (p = 0.01) and PCT (p < 0.01) levels compared to placebo. In fact, cTnT levels remained significantly lower in those assigned to colchicine, 5 days after surgery (0.14 vs 0.23 μg/L, p = 0.001).

This findings led the authors to concluded that a short perioperative course of colchicine lowered post-operative biomarkers of myocardial injury and inflammation.

Citation
Pan T et al. The low-dose colchicine in patients after non-CABG cardiac surgery: a randomized controlled trial. Crit Care 2023

Cardiac biomarkers offer no benefit to CV risk stratification in psoriasis disease

24th March 2022

Although two cardiac biomarkers are associated with cardiovascular events in psoriasis disease they are of no value in CV risk stratification

Two cardiac biomarkers, cardiac troponin I and N-terminal pro-brain-type natriuretic peptide (NT-proBNP), although independently associated with an increased risk of incident cardiovascular events (CV) in patients with psoriasis disease, offer no additional benefit when added to cardiovascular risk stratification tools.

This was the finding of a longitudinal study by researchers from the Women’s College Hospital, Toronto, Canada.

Patients with both psoriasis and psoriatic arthritis, collectively referred to as psoriasis disease, have an increased risk of cardiovascular disease. For instance, one meta-analysis found that patients with psoriatic arthritis had a 43% increased risk of cardiovascular diseases compared with the general population.

Furthermore, among those with psoriasis, but without the inflammatory arthritis, there is also an apparent higher risk of both cardiovascular disease and cardiovascular risk factors, although only among those with more severe disease.

While part of the reason behind this increased risk of cardiovascular disease can be explained due to the presence of traditional risk factors such as smoking, physical inactivity etc, patients with psoriasis have been shown to have increased vascular, subcutaneous and hepatic inflammation.

The use of population-based risk algorithms like the Framingham Risk Score (FRS) are widely used in risk stratification for the development of CV events, such algorithms may underestimate long term risk of major adverse cardiac events in psoriasis patients.

Elevated levels in the general population of the cardiac biomarker high cardiac troponin is associated with increased CVD risk. In addition, among older people with type 2 diabetes, NT-proBNP was strongly associated with subsequent risk of all cardiovascular disease events. Moreover, elevated NT-proBNP levels have a mortality predictive value in patients with rheumatoid arthritis. While both cardiac troponin I and NT-proBNP are useful cardiac biomarkers in the general population, whether the two markers add value for the risk stratification of patients with psoriasis disease is uncertain.

For the present study, the researchers evaluated the association between cardiac troponin I and NT-proBNP and a marker of CV risk, the presence and progression of carotid atherosclerosis, assessed by the carotid total plaque area (TPA). They recruited patients with psoriasis disease and a cohort who had undertaken a baseline and subsequent carotid ultrasound assessment of atherosclerosis. For all participants, Framingham risk scores, which includes several factors such as age, gender, smoking status, systolic blood pressure, diabetes etc were calculated, to estimate their 10-year risk of CV. The researchers set the primary end point as the occurrence of the first CV event which was a composite outcome including angina, myocardial infarction, ischaemic cerebrovascular accident and cardiovascular death.

Cardiac biomarkers and CV events

A carotid ultrasound was performed on 358 individuals and the mean duration of follow-up was 3.69 years. After adjustment for CV risk factors, the association between baseline TPA and cardiac troponin I remained significant but not for NT-proBNP. However, this association was no longer significant for atherosclerosis progression.

During a follow-up of 7.1 years there were 64 incident CV events, giving a rate of 0.90 events per 100 person-years. Both cardiac troponin I (hazard ratio, HR = 3.02, 95% CI 1.12 – 8.16) and NT-proBNP (HR = 2.02, 95% CI 1.28 – 3.18) were significantly associated with CV events per one standard deviation increase.

However, inclusion of both biomarkers into the FRS this did not improve the diagnostic accuracy of the score. In other words, while cardiac troponin I was associated with atherosclerotic burden, it had no subsequent predictive value as the level of atherosclerosis increased.

Furthermore, while it was clear that the two biomarkers were associated with a higher risk of a CV event, adding these into the FRS did not improve the overall diagnostic accuracy for predicting CV events.

They concluded that the use of both biomarkers while predictive of CV events in the general population, did not aid CV risk stratification in patients with psoriasis disease.

Citation
Colaco K et al. Association of Cardiac Biomarkers with Cardiovascular Outcomes in Patients with Psoriatic Arthritis and Psoriasis: A Longitudinal Cohort Study Arthritis Rheumatol 2022

Could abdominal aortic calcification and troponin levels be prognostic for risk of ASVD in older women?

28th January 2022

Higher abdominal aortic calcification and cardiac troponin 1 levels are associated with a higher ASVD and all-cause mortality in older women

The co-presence of higher abdominal aortic calcification (AAC) and cardiac troponin 1 (hs-cTn1) levels is associated with a greater risk of atherosclerotic vascular disease (ASVD) and all-cause mortality in older women. This was an important finding by researchers from the Medical School, The University of Western Australia, Perth, Australia.

Atherosclerosis is the underlying cause of cardiovascular disease (CVD) and as many as 1 in 3 deaths in women are due to CVD. Evidence also suggests that women tend to experience adverse cardiovascular outcomes such as an acute myocardial infarction, on average, 9 years later than men although from the age of 55, men and women have similar lifetime risks of cardiovascular disease. This parity of risk yet difference in the time for an adverse cardiovascular outcome, suggests a gap in the understanding of cardiovascular disease risks, especially in older women.

The presence of higher levels of abdominal aortic calcification obtained from imaging has been shown to have a have substantially greater risk of future cardiovascular events and poorer prognosis, particularly in older women. Furthermore, higher cardiac troponin I levels have been shown to be independently associated with future cardiac events in elderly women without apparent clinical manifestations. But could measurement of both of these values be of prognostic value in determining the risk of ASVD mortality in older women?

This was the question addressed by the Australian team, who set out to determine whether measurement of AAC and hs-cTn1 levels could be used to provide information on ASVD and all-cause mortality risk in older women.

The team followed up community dwelling women between 2003 and 2013 and for whom AAC and hs-cTn1 values had been measured in 2003. Both AAC and hs-cTn1 measurements were combined into four distinct groups: a low AAC and < median hs-cTn1 (group 1) ; moderate AAC and < median hs-cTn1 (group 2) ; low AAC and > median hs-cTn1 (group 3) and finally, moderate-extensive AAC and > median hs-cTn1 (group 4). For the purposes of their analysis, group 1 served as the reference point.

Findings

The total population included 908 women with a mean age of 79.4 years and 34.9% of whom had moderate-extensive AAC and > median hs-cTn1, i.e., group 4.

When considered separately, compared to women in group 1, those in group 4 had an 84% increased risk of 10-year ASVD mortality and a 37% higher risk of all-cause mortality based on AAC values. Similarly for hs-cTn1, those in group 4 had a 141% increased risk of ASVD mortality and a 106% higher risk of all-cause mortality.

In multivariable adjusted models including both AAC and hs-cTn1, the adjusted hazard ratios for ASVD mortality, compared to group 1 increased from 2.39 (95% CI 1.05 – 5.56, p = 0.039) for group 2, to 3.18 (group 3) and finally 5.38 for group 4, all of which were statistically significant.

Similar increases were observed for all-cause mortality, peaking at an adjusted hazard ratio of 3.02 (95% CI 1.93 – 4.72, p < 0.001) for group 4.

Based on these findings, the authors concluded that these two simple and quick measures were robustly associated with 10-year ASVD and all-cause-related mortality.

Citation

Teh R et al. Abdominal aortic calcification, cardiac troponin I and atherosclerotic vascular disease mortality in older women Heart 2021