A proposed model using glycation metrics and circulating biomarkers for the prevention of cardiovascular disease

Abstract

Introduction: Cardiovascular aging starts early in life due to the glycation of critical proteins, though its progression remains undetected in the formative years. The glycation reaction affects all tissues by the same non enzymatic irreversible reaction. The variables are the pH, temperature, glucose concentration, and the specific protein. This relationship implies that glycated blood biomarkers could potentially be used as a proxy for assessing in situ myocardial changes.

Methods: Laboratory tests for troponin I (cTnI), hemoglobin A1c (A1c), fructosamine, and low-density lipoprotein (LDL), were chosen to calculate the proxy for in situ glycation. An algorithm was developed incorporating these variables as individual measurements and as calculated metrics of glycation. This data was obtained from previous large group studies of variables and outcomes.

Results: Modeling of glycation was determined for each variable. Using metrics from multiple studies, theoretical rates of glycation of LDL and troponin I were calculated. The glycated changes in LDL and troponin I were used to determine the increases above optimal physiological rates.

Conclusion: Laboratory results of LDL, cTnI, A1c and fructosamine could be used sequentially to derive a cost-effective proxy for assessing in situ aging and deterioration of cardiovascular tissue. This model could theoretically predict the rate of cardiovascular aging by integrating four blood biomarkers into a dedicated algorithm guiding proactive diagnostics and treatment.

Keywords: algorithm; biomarkers; cardiovascular disease; glycation; prevention.

Figure 1

Schematic drawing of the glycation reaction.

Figure 2

Comparison of Troponin I glycation index (TGI) over 30 years for one individual developing prediabetes and one normal individual. Initial reference point at age 25 for both was with the same optimal reference TGI of 1.6, A1c 31 mmol/mol (5.0%), TGR 1.0 and cTnI 1.6 ng/L. Area under the curve (AUC) revealed a doubling of the amount of myocardial tissue glycated in the prediabetic individual compared to the normal (39/19.5).

Figure 3

Comparison of LDL glycation index (LGI) over 30 years in an individual developing prediabetes and one normal individual. Initial reference point at age 25 for both was LGI 60, A1c 31 mmol/mol (5.0%), LGR 1.0 and LDL 60 mg/dL. The area under the curve (AUC) for the individual with prediabetes demonstrated greater than twice the amount of LDL glycated compared to the normal individual (1725/765).