Chronological and biological ageing in coronary artery disease

Johnman, Cathy (2015) Chronological and biological ageing in coronary artery disease. PhD thesis, University of Glasgow.

Abstract

Background:
The elderly account for an increasing proportion of the population and have a high prevalence of coronary artery disease (CAD). Therefore, elderly patients represent an increasing proportion of those presenting for investigation and treatment of CAD. Management of CAD is undertaken to relieve the signs and symptoms of myocardial ischaemia, making quality of life (QoL) a critical consideration in clinical decision making. CAD is associated with both chronological and biological ageing processes. However, conflicting evidence exists as to whether leucocyte telomere length (LTL) is an appropriate biomarker of ageing in CAD.

Methods:
The thesis comprised four complementary studies. Firstly, secondary data analysis of the Scottish Coronary Revascularisation Register was used to undertake two retrospective cohort studies of patients attending for coronary angiography and percutaneous coronary revascularization. The aim was to compare case mix and outcomes of elderly versus younger patients. A prospective cohort study of 437 patients was then undertaken to assess QoL before, and three months after, PCI and to compare QoL changes in elderly versus younger patients. Finally a cross sectional study was used to investigate the association between LTL (T/S ratio -relative ratio of repeat to single copy number) measured using qPCR and CAD (presence and severity) in 1,846 patients attending a regional cardiovascular centre for coronary angiography.

Results:
The number and proportion of elderly patients undergoing coronary angiography increased from 669 (8.7%) in 2001 to 1,945 (16.8%) in 2010. Among the elderly (>= 75 years old), symptoms were more severe and disease more extensive compared to patients aged <75 years. Peri-procedural complications were infrequent irrespective of age: 2.0% of elderly patients suffered complications, compared with 1.6% of young patients (p<0.001). Thirty-day MACCE were more common in elderly compared with younger patients (2.0% vs 1.6%, p<0.001). Elderly patients with evidence of stenosis were less likely to proceed to revascularisation (adjusted OR 0.68, 95% CI 0.65–0.71, p<0.001) within one year of angiography, irrespective of disease severity.
There was an increase in the number and percentage of PCIs undertaken in elderly patients, from 196 (8.7%) in 2000 to 752 (13.9%) in 2007. Compared with younger patients, the elderly were more likely to have multivessel disease, multiple comorbidity, and a history of myocardial infarction or coronary artery bypass grafting (χ2 tests, all p<0.001). The elderly had a higher risk of MACE within 30 days of PCI (4.5% versus 2.7%, χ2 test p<0.001)
Following PCI, mean QoL improved in both elderly and younger patients. Elderly participants had higher baseline mental component score (MCS) but lower physical component score (PCS). After adjusting for baseline differences, QoL (both physical and mental components) in elderly patients improved as much as younger patients, following PCI (SF-12 v2 MCS 50.0(SD 10.4) to 53.0(SD 11.9) vs 46.7(SD 11.1) to 49.7(SD 11.1), p=0.652; and SF-12 v2 PCS 37.6(SD 10.1) to 41.9(SD 10.1) vs 39.7(SD 10.0) to 45.6(SD 10.8), p=0.373).
An inverse relationship was found between LTL (T/S ratio) and age. No statistically significant difference was found in mean T/S ratio between those with and without CAD (0.87(SD 0.21) vs 0.89(SD 0.21), p=0.091), even after adjusting for baseline characteristics. In addition, there was no statistically significant difference in relative T/S length by severity of disease in those found to have stenosis on cardiac angiography: 0.875 (SD 0.211) vs 0.875 (SD 0.212) vs 0.860 (SD 0.203) vs 0.867 (SD 0.200), p=0.670.

Conclusions:
This thesis has demonstrated that, in Scotland, elderly patients account for an increasing number and proportion of diagnostic coronary angiograms and PCIs. However, the threshold for investigation and subsequent intervention appears to be higher among the elderly, even after adjusting for co-morbidities. While elderly patients have a higher risk of early complications than younger patients, their absolute risk is, nonetheless, low. This suggests that coronary angiography and PCI are safe procedures to perform in the elderly. Following PCI, the QoL of elderly patients improves at least as much as in younger patients.

A recognized risk factor for CAD is chronological age, and there is increasing interest in whether biological age contributes to the development and progression of disease and can explain socioeconomic inequalities in health. However, the current thesis found no association between LTL and either the occurrence or severity of CAD, or its severity on cross-sectional study. While LTL is considered a useful biomarker of ageing, these findings suggest that LTL may not be as useful in CAD.
Although findings suggest that coronary angiography and PCI are safe procedures in the elderly, results of this thesis suggest an age-based inequality in access to coronary artery investigation and intervention that is not explained by differences in demographic trends, levels of need, potential risk or potential benefit. These findings have significant implications for the delivery of cardiovascular clinical services to an increasing elderly population. Further investigation should be undertaken upstream of these studies, on patients referred for investigation rather than just those receiving it to determine the extent to which there are inequalities in referral threshold as well as procedure threshold. Further research is also required to identify those elderly patients who would most benefit from earlier investigation and management. There is also a need for longitudinal studies to assess the usefulness of LTL as a biomarker of ageing in CAD and to investigate whether LTL is associated with adverse outcomes in patients diagnosed with CAD.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Coronary artery disease, percutaneous coronary intervention, coronary angiography, ageing
• Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Supervisor's Name: Pell, Professor J.P.
• Date of Award: 2015
• Depositing User: Dr Cathy Johnman
• Unique ID: glathesis:2015-6138
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 26 Mar 2015 08:42
• Last Modified: 04 Mar 2016 16:13
• URI: https://theses.gla.ac.uk/id/eprint/6138