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

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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Identifiers

ORCID for Suresh Giritharan: orcid.org/0000-0002-5826-0812

ORCID for Felino Cagampang: orcid.org/0000-0003-4404-9853

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