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<p>  To improve cardiometabolic health, omnivores are often recommended to simultaneously adopt a healthy dietary pattern with an emphasis on increasing intakes of plant-based proteins and decreasing intakes of red and processed meats. However, the totality of observational and experimental results inconsistently supports relations between red meat intake and risks of cardiometabolic diseases such as cardiovascular disease and type 2 diabetes mellitus. Red meat is often not clearly or consistently defined within nutrition and health research and is consumed within healthy and unhealthy dietary patterns. These issues contribute to the conflicting findings. Observational data, which assess red meat (both unprocessed and processed) within an unrestricted Western-style dietary pattern, typically support positive associations with cardiometabolic disease incidence and mortality outcomes. Whereas experimental randomized controlled trial data consistently show that consuming healthy dietary patterns with or without the inclusion of lean unprocessed red meat, improve cardiometabolic disease risk factors. These discordant findings have left laymen, researchers,and policymakers alike to question whether a high intake of red meat is causally related to cardiometabolic disease outcomes. The results of the single blinded crossover randomized controlled feeding trial (Study 1, Chapter 3) support that consuming a U.S.-style healthy dietary pattern that included two 3oz servings/day of lean unprocessed beef did not adversely affect cardiometabolic disease risk factors. Based on observational and experimental research, the umbrella systematic review described in Chapter4, led to the inference that red and processed meats are not causally related with cardiovascular disease. However, relations between processed meat and mixed unprocessed and processed meat and type 2 diabetes were inferred to be potentially causal. Overall, the results described in this dissertation support that lean and unprocessed red meats consumed within healthy dietary patterns do not adversely affect cardiometabolic health</p>

For most children, occult vascular damage is minimal and has a slow rate of progression likely due to the existence of healthy lifestyles and the prevalence of preventative behaviours. However, there is evidence to suggest a marked increase in the prevalence of traditional and emerging cardiovascular risk factors in children with chronic inflammatory conditions due to the common aetiology pathways of inflammation and atherosclerosis. In the current cross-sectional study, a comprehensive vascular assessment was conducted on 21 children with various chronic inflammatory conditions including juvenile idiopathic arthritis (JIA), cystic fibrosis (CF), type I diabetes mellitus (T1DM) and inflammatory bowel disease (IBD) (CIC, 12.7 ± 2.3 years) compared to 9 healthy, age and sex- matched controls (CON, 13.1 ± 1.8 years). B-mode ultrasound images were used to assess carotid artery intima media thickness (cIMT) as well as local arterial stiffness through measurement of compliance and distensibility with the use of concurrent applanation tonometry. Whole-body arterial stiffness was measured by assessing pulse wave velocity (PWV) between the carotid and dorsalis pedis arteries. A brachial flow mediated dilation (FMD) test was implemented to assess endothelial function of the brachial artery. Twelve hour-fasted blood samples were collected and analyzed for blood lipids and an acute inflammatory marker, C-reactive protein (CRP). There were no group differences in cIMT (p=0.18), distensibility (p=0.40), compliance (p=0.88), whole body PWV (p=0.74) or LDL- cholesterol (p=0.99). The CIC group demonstrated significantly lower FMD when iii compared to CON (p=0.01). There were no group differences in inflammatory levels, as indicated by concentration of CRP (p=0.63). Sub-analyses revealed similar cIMT, distensibility, compliance, PWV and LDL levels between children with JIA (n=11, 12.6 ± 2.9 years), CON (n=9, 13.1 ± 1.8 years) and the other inflammatory conditions (INFL, n=10, 12.4 ± 1.7 years). Both JIA and INFL reported lower FMD when compared to CON (p=0.04). INFL had lower BMI compared to JIA and CON (p=0.02). The primary findings from this study suggest that arterial structure is similar between children with a CIC and their healthy peers; however, arterial function, as indicated by FMD (%), was reduced in the CIC group. This finding is essential in that it helps to identify an area for targeted intervention and/or prevention of future CV events as endothelial dysfunction is known to be an early event in the pathophysiology of atherosclerosis. / Thesis / Master of Science (MSc)

Introduction: There are no economic evaluations to determine the value of PRSs. The objective of this study was to determine if the addition of a PRS to traditional risk factors to guide statin therapy is a cost-effective intervention for the prevention of primary MI cases in the Ontario healthcare payer perspective. Methods: A PRS cost-effectiveness model was constructed to produce various statin prescription strategies in conjunction with the FRS. Upper PRS thresholds (between 25% to 70%) were set such that individuals falling into them would be eligible for statins while those in lower PRS thresholds (between 1% to 25%) were deemed protected and removed from consideration. The model determined number of incident MIs saved or not saved by statins, costs, quality of life, and the effect of statins on preventing MIs over a 10-year time horizon, discounted at 1.5% annually. One-way sensitivity analysis and a PSA were performed by varying all model parameters. Non-related participants of white British descent from 96,736 participants in the UK Biobank at intermediate risk for cardiovascular disease, determined using the Canadian Cardiovascular Society dyslipidemia guidelines of 2016, were used for the study. Results: The optimal clinical and economic strategy was one whereby the top 70% PRS individuals are eligible for statins, with the lower 5% PRS excluded. A base-case analysis at a PRS cost of $70 produced an ICER of $747,184.10/QALY, ranging from $525,678.90/QALY to $930,144.40/QALY in a one-way sensitivity analysis. In the PSA, the intervention has approximately a 50% probability of being cost-effective at $750,000/QALY. At a genotyping cost of $0, statin strategies guided by PRS dominated standard care when at least 12% of the lower PRS individuals were withheld from statins. When the predictive performance of the PRS is increased, the ICER drops drastically depending on the cost of genotyping and statin strategy. Conclusion: The cost-effectiveness model considers MI cases exclusively and a short, 10-year time horizon which likely overestimate the ICER. However, this study elucidates that the PRS has the potential to be extremely cost-effective in the future. / Thesis / Master of Science (MSc) / Approximately 1 in 3 Canadians live with at least one genetically linked chronic disease. Together, these diseases constitute a large economic burden on the healthcare system and well-being of individuals. Recent advancements in genetics allow risk prediction of developing complex, but common chronic diseases such as cardiovascular disease. Termed as polygenic risk scores, they have the potential to carry beneficial clinical outcomes such as an improved quality of life. However, the economics is not yet understood. This study determined that when targeting heart attacks, approximately $750,000 is required to gain an additional life-year for an adult. Although this may seem high, the result is closer to an upper-limit estimate than the true cost since polygenic risk scores have more benefits than solely for heart attacks. In the future, when accounting for their entire potential, the cost per life-year is likely to be lower, and perhaps even a money-returning investment.

Contexte : Les mécanismes entre la force de préhension et les maladies cardiovasculaires demeurent peu documentés et mal compris. Objectifs : L’objectif de cette thèse consiste à examiner le rôle de la force de préhension sur le risque cardiovasculaire. Spécifiquement, 1) Explorer la conceptualisation du sexe biologique dans l’association entre la force de préhension et les issues cardiovasculaires; 2) Investiguer l’association entre la force de préhension et l’athérosclérose vasculaire; 3) Décomposer le rôle médiateur et d’interaction de la force de préhension dans les associations entre les facteurs de risque cardiovasculaire et l’athérosclérose vasculaire. Méthodes : Pour l’objectif 1, nous avons réalisé un examen de la portée à partir du cadre méthodologique d’Arkey et O’Malley. Les objectifs 2 et 3 ont été investigués à partir des données de l’Étude longitudinale canadienne sur le vieillissement. Les méthodes de Randomisation mendélienne et de décomposition à 4 portions ont été respectivement utilisées pour répondre à ces deux objectifs. Résultats : Les résultats de l'examen de la portée ont montré qu'il existe peu d'étude examinant les différences entre les sexes dans l'association entre la force de préhension et les maladies cardiovasculaires. Nos résultats de Randomisation mendélienne suggèrent une association statistiquement significative entre la force de préhension et l’athérosclérose vasculaire (coefficient RM de 0,02 mm (IC à 95 % : 0,01 ; 0,05)), sans différence entre les sexes (p-value = 0,201) et les groupes d'âge [(≤ 60 ans contre > 60 ans) ; p-value = 0,421]. La force de préhension joue rôle médiateur entre l’activité physique et l’athérosclérose [effet indirect pur (IC à 95 %) = 0,13 (0,10 ; 0,17) et 0,08 (0,01 ; 0,11) pour les hommes et les femmes respectivement], mais pas entre diabète de type 2/hypertension et l’athérosclérose [effet indirect pur (IC à 95 %) allant de 0,01 (-0,03; 0,05) à 0,05 (-0,02; 0,07)]. Les termes d'interaction étaient positifs et estimés avec une précision suffisante (allant de 0,03 (0,01; 0,05) à 0,10 (0,07; 0,16)), suggérant la présence d'interactions synergiques entre les facteurs de risque cardiovasculaire et la force de préhension sur l’athérosclérose vasculaire. Les effets conjoints estimés variaient de 0,15 (IC à 95 % : 0,12; 0,17) à 0,32 (IC à 95 % : 0,29; 0,38). Les pourcentages dus à l’interaction étaient plus élevés chez les hommes (allant de 17,3 % à 65,5 % de l'effet total) que chez les femmes (allant de 15,2 % à 37,9 % de l'effet total). Conclusion : Les résultats de cette thèse suggèrent que l'amélioration de la force de préhension pour réduire le risque cardiovasculaire devrait être une priorité égale pour les hommes et les femmes. Elle apporte des éclaircis pour la formulation des stratégies d'intervention de santé publique portant tant sur l’amélioration de la force de préhension que sur la réduction du risque cardiovasculaire, tout en recommandant une attention sur les mécanismes biologiques pouvant expliquer l'association entre la force de préhension et le risque cardiovasculaire. / Background: The mechanisms between grip strength and cardiovascular disease remain poorly documented and misunderstood. Objectives: The objective of this thesis is to examine the role of grip strength on cardiovascular risk. Specifically, 1) Explore the conceptualization of biological sex in the association between grip strength and cardiovascular outcomes; 2) Investigate the association between grip strength and vascular atherosclerosis; 3) Decomposing the mediating and interacting role of grip strength in the associations between cardiovascular risk factors and vascular atherosclerosis. Methods: For objective 1, we conducted a scoping review using the methodological framework of Arkey and O'Malley. Objectives 2 and 3 were investigated using data from the Canadian Longitudinal Study on Aging. Mendelian randomization and 4-ways decomposition methods were respectively used to meet these two objectives. Results: The results of the scoping review showed that there are few studies examining biological sex-differences in the association between grip strength and cardiovascular disease. Our Mendelian Randomization results suggest a statistically significant association between grip strength and vascular atherosclerosis (RM coefficient of 0.02 mm (95% CI: 0.01; 0.05)), with no difference between sexes (p -value = 0.201) and age groups [(≤ 60 years versus > 60 years); p-value = 0.421]. Grip strength mediates the association between physical activity and vascular atherosclerosis [pure indirect effect (95% CI) = 0.13 mm (0.10; 0.17) and 0.08 mm (0.01; 0.11) for males and females respectively], but not between type 2 diabetes/hypertension and vascular atherosclerosis [pure indirect effect (95% CI) ranging from 0.01 (-0.03; 0.05) to 0.05 (-0 .02; 0.07)]. Interaction terms were positive and estimated with sufficient precision (ranging from 0.03 (0.01; 0.05) to 0.10 (0.07; 0.16)), suggesting the presence of synergistic interactions between cardiovascular risk factors and grip strength on vascular atherosclerosis. Joint effects estimates ranged from 0.15 (95% CI: 0.12; 0.17) to 0.32 (95% CI: 0.29; 0.38). The percentages due to interaction were higher in males (ranging from 17.3% to 65.5% of the total effect) than in females (ranging from 15.2% to 37.9% of the total effect). Conclusion: The results of this thesis suggest that improving grip strength to reduce cardiovascular risk should be an equal priority for males and females. It sheds light on the formulation of public health intervention strategies relating both to the improvement of grip strength and to the reduction of cardiovascular risk, while recommending attention to the biological mechanisms that may explain the association between grip strength and cardiovascular risk.

Bakgrund Kranskärlssjukdom är ett av världens stora hälsoproblem där både insjuknandet och dödligheten är hög.Det finns god evidens för att träningsbaserad hjärtrehabilitering minskar mortaliteten och behovet avsjukhusvård. Trots detta är det i Sverige endast 20% av patienterna som deltar i träning inomcenterbaserad hjärtrehabilitering. En vanlig orsak till lågt deltagande är långa avstånd. Träning förmedladvia E-hälsa har potential att kunna öka tillgängligheten till hjärtrehabilitering. Innan implementeringbehöver effekten utvärderas. Syfte Syftet är att genom en systematisk litteraturöversikt jämföra effekten av träningsbaseradhjärtrehabilitering i klink med träningsbaserad hjärtrehabilitering på distans med hjälp av digital teknik. Metod Den systematiska litteraturöversikten utfördes genom artikelsökningar från databaserna PubMed ochCinahl. Söksträngarna formulerades enligt PICO-modellen. Därefter granskades artiklarna och bedömdesför bias enligt SBU:s formulär ”Bedömning av randomiserade studier”. Resultat Tretton artiklar uppfyllde inklusionskriterierna. De former av E-hälsa som användes varmobilapplikationer, websidor, telefonkontakt, SMS, mail och videomöten. Syreupptagningsförmåga mätt iVo2 peak eller Vo2 max var likvärdig eller bättre i interventionsgrupperna (E-hälsa) jämfört medkontrollgrupperna (sedvanlig vård). Följsamhet till träningen rapporterades vara bättre iinterventionsgruppen än kontrollgruppen och den självskattade livskvalitén som lika god iinterventionsgrupperna jämfört med kontrollgrupperna. Konklusion Resultaten tyder på att träningsbaserad hjärtrehabilitering förmedlad via E-hälsa kan vara lika effektivsom centerbaserad hjärtrehabilitering. Att använda E-hälsa som ett kompletterande hjälpmedel skullekunna göra träning inom hjärtrehabilitering mer lättillgänglig och öka både deltagande och följsamhet.

<p dir="ltr">Hemorrhage and aortic aneurysms result from external or internal damage to a vessel wall and can be lethal if timely interventions are not made. Blood clotting and thrombus sometimes have a negative connotation in the medical community, but the coagulation cascade is a vital response to hemorrhage and disease. For hemorrhage, the coagulation cascade forms a plug at the injury site providing potentially life-saving hemostasis. In aortic aneurysms, blood coagulates inside the vessel or vessel wall to form intraluminal or intramural thrombus. The role of intraluminal and intramural thrombus in aneurysm rupture remains poorly understood, but past research suggests it may protect against further vessel damage dependent on its location and time of deposition. My dissertation focuses on application of a new photocurable sealant that surrounds a wound and aids in the coagulation cascade during hemorrhage, and analysis of the intramural and intraluminal thrombus that forms in aortic dissections and abdominal aortic aneurysms, respectively. We used volumetric and pulsed-wave Doppler ultrasound to detect changes in hemodynamics, vessel morphology, aneurysm thrombus deposition, and tracked the photocurable sealant’s performance and degradation <i>in vivo</i>. We used novel scanning electron microscopy analysis techniques in aortic aneurysm studies to uncover and quantify new information about thrombus structure. Our characterization and <i>in vivo </i>feasibility study with the photocurable sealant can serve as evidence for translation to future use in humans, and our techniques and findings in murine aneurysm models can potentially be used to elucidate the role and structure of thrombus in human aortic aneurysms.</p>

Accounting for nearly 19% of the United States population in 2020, Latinos and Hispanics represent the second largest racial/ethnic group in the United States, totaling roughly 62.1 million people. Given the growing population size and longer life expectancy estimates amongst the U.S. Latino/Hispanic community, healthcare practitioners and public health officials are increasingly emphasizing the healthcare needs and outcomes of this population. Alarmingly, current literature has highlighted significant disparities in cardiovascular disease (CVD) incidence and risk factors among U.S. Latinos/Hispanics. As CVD continues to be one of the leading causes of death amongst all racial/ethnic groups across the United States, risk reduction through preventative care utilization remains of utmost importance for mitigating potential risk factors and eventual diagnosis of CVD. The purpose of the study was to quantify healthcare engagement through preventive care utilization for cardiovascular disease and associated risk factors among U.S. Latino/Hispanics. This research study used a cross-sectional design with secondary data from the 2017- March 2020 National Health and Nutrition Examination Survey (NHANES). Variables related to sociodemographic characteristics, knowledge of CVD/risk factor history, and preventive service utilization for CVD were collected from a sample of N=2122 adult Latino/Hispanic participants, representing 40,412,679 U.S. Latinos/Hispanics. All 9 demographic variables were found to have significant associations with the 7 preventive service use variables (p<.001-.016). Similarly, most of the 11 variables related to knowledge of CVD history were found to have significant associations with the 7 preventive service use variables (p<.001). No significant associations were found between knowledge of high blood pressure history with medication use, and knowledge of diabetes history with A1C testing use. Findings from this study reveal various disparities in CVD preventive care utilization amongst the study participants. Limitations of this study included lack of disaggregated ethnic data, possible bias in self-reported data, and missing responses. Results from this study can be utilized to inform clinicians and public health officials in establishing personalized preventive care interventions and increasing community engagement with cardiovascular preventive care services.

The dose-response relationship between physical activity (PA), disease and mortality has primarily been obtained from self-report questionnaires in Western populations. A major limitation of self-reported PA is the likelihood of measurement error and these recordings cannot account for all 24-h activities, thus negating the influence of sedentary time and daily light intensity activity. Modern-day studies using objective measures of PA are highly controversial in the description of PA, as well as reliable wear time of these objective devices to accurately assess PA behaviour. The aim of the research presented in this thesis was to ascertain the associations between seven-day objectively measured PA (expressed as time spent in four different metabolic equivalent of task (MET) categories), cardiovascular disease risk factors (24-h ambulatory blood pressure and central obesity), chronic stress (General Health Questionnaire total score and serum cortisol) and DNA damage (leukocyte telomere length) in a cohort of African and Caucasian school teachers recruited from the Dr Kenneth Kaunda Education District in the North West Province of South Africa. All parameters were objectively measured (the GHQ was only added for thoroughness on measures of cognitive perceived stress) in the study population. The Africans (n=96) were younger than the Caucasians (n=107) (48.33 versus 51.06 years, p=0.024), but presented with slightly higher waist circumferences, significantly higher 24-h ambulatory systolic blood pressure (SBP, p≤0.000), diastolic blood pressure (DBP, p≤0.000) and mean arterial pressure (MAP, p≤0.000); significantly higher perceived stress scores (GHQ total scores, p=0.001) and significantly shorter telomeres (p≤0.000). The hypertensive participants in the total group (Africans and Caucasians combined) recorded 2.2 hours (12.4%) more daily awake sedentary time than the normotensive participants (p=0.004) and sedentary time was also a slightly better predictor of hypertension than moderate and vigorous activity time (Odds ratio=1.00, p=0.006). Irrespective of race and sex, 24-h SBP and DBP measurements were respectively associated with daily awake sedentary time (ß=0.17, p=0.018 and ß=0.18, p=0.020), light activity time (ß=-0.15, p=0.043 and ß=-0.16, p=0.041), waist circumference (ß=0.45, p≤0.000 and ß=0.33, p≤0.000) and log serum gamma glutamyl transferase (γ-GT, alcohol use) (ß=0.18, p=0.018 and ß=0.24, p=0.004). An older age (ß=-0.28, p≤0.000), higher alcohol consumption (ß=-0.21, p=0.003) and increased central obesity (ß=-0.17, p=0.017) were associated with shorter telomeres. Attenuated cortisol levels (ß=-0.12, p=0.068) showed a tendency towards associations with longer telomeres that may indicate possible cortisol down regulation to protect against DNA damage. Time spent in the different MET-categories showed no direct associations with either cortisol or telomere length. However, a sensitivity analysis indicated that daily light intensity activity time was significantly correlated with lower waist circumference (r=-0.21, p=0.004); a parameter associated with both cortisol (ß=-0.22, p=0.003) and telomere length (ß=-0.17, p=0.017). The thorough recording of PA during the true awake time of 24-h cycles over a period of seven days ensured that the beneficial effect of light intensity activities, as well as the detrimental effect of sedentary time, was highlighted by this study. The average awake time of all ethnic and sex groups were around 17 hours per day, which was more than most previous studies using objective measures of PA. The exclusion of participants who did not comply through wearing the Actiheart for a full seven days (n=143, 40%) did, however, have a negative impact on sample size that may have affected the statistical power for uncovering some significant associations and the high participant burden of the Actiheart device became clear. Therefore, the researchers used the data of the full seven-day recordings to also determine the minimum number of consecutive days the Actiheart device could be worn to accurately estimate energy expenditure and PA. The two-day combination of Wednesday-to-Thursday did not differ from the weekly average TEE, as well as for all MET-categories in all ethnic and sex groups. This two-day combination is practically convenient and would lessen participant burden. Future researchers are urged to test this combination in other populations to standardize Actiheart wear time. It can be concluded from the findings in this study that less daily awake sedentary time, more light intensity activity time, as well as lower alcohol consumption favour improved health as it is beneficial to 24-h ambulatory blood pressure and helps to maintain a healthy waist circumference, which ultimately influence telomere shortening. Furthermore, the two-day combination of Wednesday-to-Thursday seems to be sufficient to accurately estimate weekly energy expenditure and habitual PA with the Actiheart apparatus. / PhD (Human Movement Science), North-West University, Potchefstroom Campus, 2015