Exercise blood pressure & cardiovascular disease : clinical & methodological considerations

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, with the number one risk factor being high blood pressure (BP). The diagnosis and management of high BP has been traditionally made based on BP measured in a clinic setting under resting conditions. Based on this mode of assessment, it was estimated that in 2019 over 1.2 billion adults worldwide had high BP. However, many more people have high BP that is either not diagnosed or well-controlled. Indeed, 8-20% of individuals with normal clinic BP have high BP when measured outside of the clinic (based on gold-standard ambulatory BP monitoring) and thus remain at elevated CVD risk. Since out-of-clinic BP monitoring is not always available, alternative methods are needed to improve the identification and management of high BP and its related CVD risk. Recent research indicates that an abnormally high BP response to dynamic exercise (termed a hypertensive response to exercise; HRE) is an independent signal for future cardiovascular morbidity, events and mortality, likely because of high BP missed by standard clinic (resting) BP. Whilst this work highlights the potential importance of measuring the BP response to exercise for the identification of high BP-related CVD risk, there are still several key gaps in the clinical understanding of exercise BP. Indeed, several CVD risk factors may influence the BP response to exercise, but the specific nature of these relationships is unknown, and whether CVD risk is different in those with an HRE remains unclear. Additionally, several factors that relate to how exercise BP is measured (i.e. methodological considerations) may influence clinical interpretation of the exercise BP response. Thus, the broad aims of this research were to determine: (1) the relationship between exercise BP and individual CVD risk factors and (2) if some methodological factors may influence clinical interpretation of exercise BP. Manual measurement of BP during an exercise test is the recommended standard, but automated BP measurement is an alternative method routinely used in clinical settings. Study 1 (Chapter 2) was undertaken to determine the concordance between manual and automated BP during a standard treadmill exercise test in 41 individuals with type 2 diabetes mellitus (66±5 years; 54% male). Concordance between manual and automated BP across all exercise stages was found to be excellent for systolic BP (intraclass correlation=0.964 [95% confidence intervals: 0.942‐0.977]). Concordance between manual and automated diastolic BP across all exercise stages was found to be moderate-to-good (intraclass correlation=0.784 [95% confidence interval: 0.672‐0.858]). These results highlight that automated measurement of BP may be a suitable alternative to manual measurement of BP during clinical exercise testing among individuals with type 2 diabetes mellitus. Study 2 (Chapter 3) was a systematic review and meta-analysis to (1) assess the relationship between exercise BP and cardiac structure, and (2) determine if cardiac structure is different in those with an HRE, across various study populations (including those with or without high BP at rest). Exercise systolic BP (at any intensity) was associated with increased left ventricular (LV) mass, LV mass index, relative wall thickness, posterior wall thickness and interventricular septal thickness (p<0.05 all). Those with an HRE (recorded at any intensity) had higher risk of LV hypertrophy, increased LV mass, LV mass index, relative wall thickness, posterior wall thickness, interventricular septal thickness and left atrial diameter vs. those without an HRE (p<0.05 all). Results were broadly similar between studies with different population characteristics and highlight the potential hypertension-related CVD risk associated with an HRE. A second systematic review and meta-analysis was performed as Study 3 (Chapter 4) to examine the relationship between exercise BP and general CVD risk factors. This study also aimed to determine if CVD risk was higher in those with an HRE compared to those without an HRE across different study populations (including those with or without high BP at rest). Exercise systolic BP (at any intensity) was associated with arterial, lipid and kidney function-related CVD risk markers (p<0.05 all). Those with an HRE (during any intensity) had greater arterial stiffness, elevated metabolic and lipid profiles, a higher degree of inflammation, and lower kidney function than those without an HRE (p<0.05 all). The poorer CVD risk profile among those with an HRE was also consistent amongst population groups with or without high BP at rest. These results suggest that an HRE should be considered an important indicator of heightened CVD risk. To gain a deeper understanding of the relationships between CVD risk factors and exercise BP, Study 4 (Chapter 5) was conducted with the aim to quantify the various pathways of association between CVD risk factors and exercise BP, whilst also determining what CVD risk factor/s were most-strongly related to exercise BP. This study was a cross-sectional analysis of data from 660 participants (44.3±2.6 years; 53% male) in the Childhood Determinants of Adult Health 3 study that had BP measured during a submaximal exercise test. Most CVD risk factors were found to be associated with exercise systolic BP via a relation with clinic (resting) BP (p<0.05 all). Clinic BP, waist-to-hip ratio and cardiorespiratory fitness were the variables most-strongly associated with exercise systolic BP (p