Complemental impact of LDL-cholesterol levels and microbiota-derived metabolites on coronary plaque burden and composition
Final Report Abstract
During my research fellowship, I in depth evaluated the interplay of risk factors and their association with major adverse cardiovascular events and coronary atheroma progression as determined by serial IVUS imaging. A first project evaluated the impact of longitudinal hsCRP assessment on incident MACE and could show that serial hsCRP measurements provide incremental information for cardiovascular risk assessment above baseline hsCRP and traditional cardiovascular risk factors in otherwise optimally treated patients with high-risk vascular disease. Interestingly, we observed this strong association of longitudinal hsCRP with MACE despite the fact that the majority of patients still harbored hsCRP levels at baseline and on-treatment that were on average within the 2 mg/L envelope. Looking at different components of the combined MACE endpoint, we found significant associations for longitudinal hsCRP with all-cause death, cardiovascular death, myocardial infarction, stroke, and coronary revascularization therapy. These findings suggest that longitudinal hsCRP may represent a novel independent marker of residual cardiovascular risk, supporting further work exploring the potential diagnostic and therapeutic implications of these findings. Based on the experience gained on methodical and statistical analyses, I consecutively evaluated the association of risk factor interaction with coronary atheroma progression as quantified by serial IVUS assessment. A second project evaluated the precise impact of on-treatment HbA1c on coronary plaque progression. We could show that on-treatment HbA1c levels associated with changes in coronary atheroma and incident MACE, independent of baseline HbA1c levels and traditional cardiovascular risk factors. Of notice, we observed no relevant difference of the association of on-treatment HbA1c with coronary plaque progression in patients with and without diabetes. These findings support the notion of a direct, specific effect of glycemic control upon the natural history of coronary atheroma and atherosclerotic events, supporting the rationale of therapies designed to specifically modulate it. To further understand the interaction of risk factors on coronary plaque progression, we evaluated the influence of aging on changes in coronary atheroma in presence and absence of risk factor control. Male patients in the group of <50 years of age showed on average no relevant coronary plaque progression, while we observed a signal towards a relevant coronary atherosclerosis progression in all other age groups. In contrast, for female patients, a relevant annualized progression in plaque burden was first observed in the age group >60 years of age. When evaluating the association of age with changes in coronary atheroma, effect sizes were strengthened when adjusting for traditional cardiovascular risk factors. Following this observation, we evaluated the link between age and changes in plaque burden in patients with good risk factor control (LDL-cholesterol <70mg/dL and systolic blood pressure <130mmHg) with patients with partial risk factor control (LDL-cholesterol <70mg/dL or systolic blood pressure <130mmHg) and patients with poor risk factor control (neither LDL-cholesterol <70mg/dL nor systolic blood pressure <130mmHg). Here we found that largest effect sizes for the association of aging with plaque progression were observed, when LDL-cholesterol and systolic blood pressure were optimally controlled, whereas no link between age and changes in plaque burden were present, when both LDL-cholesterol and systolic blood pressure are elevated. These observations led to the conclusion that aging associates with coronary atheroma progression independently of traditional cardiovascular risk factors. However, in the setting of poor risk factor control, the influence of aging on coronary artery disease progression is attenuated. Taken together, the finding acquired during the research fellowship add to the understanding of the natural progression of coronary atherosclerosis based on the patient’s age and risk factor control as well as their interaction.
Publications
- Early Resolution of New-Onset Left Bundle Branch Block After Transcatheter Aortic Valve Implantation With the SAPIEN 3 Valve. Am J Cardiol.;168:117-127.
Isogai T, Dykun I, Agrawal A, Shekhar S, Tarakji KG, Wazni OM, Kalra A, Krishnaswamy A, Reed GW, Kapadia SR, Puri R.
(See online at https://doi.org/10.1016/j.amjcard.2021.12.032) - Evaluation of the 2021 European Society of Cardiology guidelines in pre-existing right bundle branch block patients undergoing transcatheter aortic valve implantation with a balloon-expandable valve. European Heart Journal Open.;2.
Isogai T, Dykun I, Agrawal A, Shekhar S, Tarakji KG, Wazni OM, Karla A, Krishnaswamy A, Reed GW, Kapadia SR, Puri R
(See online at https://doi.org/10.1093/ehjopen/oeac014) - HbA1c, Coronary atheroma progression and cardiovascular outcomes. Am J Prev Cardiol.;9:100317
Dykun I, Bayturan O, Carlo J, Nissen SE, Kapadia SR, Tuzcu EM, Nicholls SJ, Puri R.
(See online at https://doi.org/10.1016/j.ajpc.2022.100317) - Risk Stratification and Management of Advanced Conduction Disturbances Following TAVI in Patients With Pre-Existing RBBB. Structural heart. 100006.
Isogai T, Dykun I, Agrawal A, Shekhar S, Saad AM, Verma BR, Abdelfattah OM, Kalra A, Krishnaswamy A, Reed GW, Kapadia SR, Puri R.
(See online at https://doi.org/10.1016/j.shj.2022.100006)
