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Subclinical markers of disease burden of severe aortic stenosis in patients with type 2 Diabetes Mellitus and the Metabolic Syndrome

Subclinical markers of disease burden of severe aortic stenosis in patients with type 2 Diabetes Mellitus and the Metabolic Syndrome
Subclinical markers of disease burden of severe aortic stenosis in patients with type 2 Diabetes Mellitus and the Metabolic Syndrome
Background: Aortic valve stenosis (AS) is the most common valvular disease in the developed world with a global prevalence of around 2-9% in people over the age of 65. Patients with both Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) have been reported to have worse outcomes following aortic valve replacement surgery (AVR). Mechanisms leading to aortic valve calcification and left ventricular changes in AS patients are distinct from coronary calcification. This study aimed to identify preoperative and postoperative differences in the ventricular function of patients with severe AS undergoing AVR, and to assess the preoperative levels of selected biomarkers of lipid metabolism in three different subsets of people from a separate cohort. Methods: This thesis is comprised of two separate study cohorts. The first study involved a retrospective cohort of 367 people who underwent isolated aortic valve replacement at a secondary care cardiothoracic surgery unit in Wessex. They were subdivided into three groups; people without T2DM or MetS, people with MetS, and people with diabetes. Alongside baseline demographic and biochemical data, preoperative transthoracic parameters were collated. This was compared with 1-year postoperative transthoracic echocardiography. Changes in ventricular dimensions and mass were interrogated. The second study involved a separate, prospective cohort of forty-two participants, who were also subdivided into the same three groupings as the first study. The same demographic, biochemical and echocardiographic data was once again collated. In addition to this, serum samples were collected to test for six biomarkers of lipid metabolism. Results: The first study noted that patients with MetS and T2DM had more severe left ventricular remodelling preoperatively. Postoperatively however, these same participants experienced less reverse remodelling (a beneficial sequelae of aortic valve replacement) than patients without T2DM or MetS. The second study, which focused on adipokine and lipoprotein profiles, demonstrated that people with T2DM and MetS had increased levels of resistin, lipoprotein-A and apolipoprotein-B1 compared to the control group. The control group, on the other hand, had increased levels of adiponectin and leptin compared to the other two groups. Although variations in these markers were distinct, no direct correlation with preoperative echocardiographic findings was demonstrated. Conclusion: This thesis concludes that in essence, MetS and T2DM patients with similar presentations of severe AS have significantly worse subclinical myocardial changes. The observed differences in the levels of adiponectin, leptin, resistin, lipoprotein-A and apolipoprotein-B1 adds to the current knowledge base and ongoing understanding of these biomarkers in specific cohorts of people with MetS, T2DM and symptomatic AS.
University of Southampton
Giritharan, Suresh
ffd59575-f0c8-458d-8222-c5997baee7ae
Giritharan, Suresh
ffd59575-f0c8-458d-8222-c5997baee7ae
Cagampang, Felino
7cf57d52-4a65-4554-8306-ed65226bc50e
Ohri, Sunil K.
8aa5698c-78cf-4f59-a5af-5afa46f0348c
Torrens, Christopher
15a35713-0651-4249-8227-5901e2cfcd22

Giritharan, Suresh (2024) Subclinical markers of disease burden of severe aortic stenosis in patients with type 2 Diabetes Mellitus and the Metabolic Syndrome. University of Southampton, Doctoral Thesis, 158pp.

Record type: Thesis (Doctoral)

Abstract

Background: Aortic valve stenosis (AS) is the most common valvular disease in the developed world with a global prevalence of around 2-9% in people over the age of 65. Patients with both Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) have been reported to have worse outcomes following aortic valve replacement surgery (AVR). Mechanisms leading to aortic valve calcification and left ventricular changes in AS patients are distinct from coronary calcification. This study aimed to identify preoperative and postoperative differences in the ventricular function of patients with severe AS undergoing AVR, and to assess the preoperative levels of selected biomarkers of lipid metabolism in three different subsets of people from a separate cohort. Methods: This thesis is comprised of two separate study cohorts. The first study involved a retrospective cohort of 367 people who underwent isolated aortic valve replacement at a secondary care cardiothoracic surgery unit in Wessex. They were subdivided into three groups; people without T2DM or MetS, people with MetS, and people with diabetes. Alongside baseline demographic and biochemical data, preoperative transthoracic parameters were collated. This was compared with 1-year postoperative transthoracic echocardiography. Changes in ventricular dimensions and mass were interrogated. The second study involved a separate, prospective cohort of forty-two participants, who were also subdivided into the same three groupings as the first study. The same demographic, biochemical and echocardiographic data was once again collated. In addition to this, serum samples were collected to test for six biomarkers of lipid metabolism. Results: The first study noted that patients with MetS and T2DM had more severe left ventricular remodelling preoperatively. Postoperatively however, these same participants experienced less reverse remodelling (a beneficial sequelae of aortic valve replacement) than patients without T2DM or MetS. The second study, which focused on adipokine and lipoprotein profiles, demonstrated that people with T2DM and MetS had increased levels of resistin, lipoprotein-A and apolipoprotein-B1 compared to the control group. The control group, on the other hand, had increased levels of adiponectin and leptin compared to the other two groups. Although variations in these markers were distinct, no direct correlation with preoperative echocardiographic findings was demonstrated. Conclusion: This thesis concludes that in essence, MetS and T2DM patients with similar presentations of severe AS have significantly worse subclinical myocardial changes. The observed differences in the levels of adiponectin, leptin, resistin, lipoprotein-A and apolipoprotein-B1 adds to the current knowledge base and ongoing understanding of these biomarkers in specific cohorts of people with MetS, T2DM and symptomatic AS.

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Published date: April 2024

Identifiers

Local EPrints ID: 488834
URI: http://eprints.soton.ac.uk/id/eprint/488834
PURE UUID: e7f94908-42b8-4a62-9257-2e9b57438328
ORCID for Suresh Giritharan: ORCID iD orcid.org/0000-0002-5826-0812
ORCID for Felino Cagampang: ORCID iD orcid.org/0000-0003-4404-9853

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Date deposited: 08 Apr 2024 16:31
Last modified: 16 May 2024 01:54

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Contributors

Author: Suresh Giritharan ORCID iD
Thesis advisor: Felino Cagampang ORCID iD
Thesis advisor: Sunil K. Ohri
Thesis advisor: Christopher Torrens

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