Strengths and limitations
CKD, diabetes
DIABETES
Strengths of our study include the analysis in a well-characterized and densely phenotyped general population with well-defined outcomes, allowing for investigating multiple CVD-related endophenotypes within one general population of adequate sample size and controlling for multiple confounders. SAF, as a marker for long-term AGEs accumulation, can capture the accumulated AGE burden in tissues during a longer period than circulating markers.Several limitations are also present in the current study. Our results were restricted to the older Dutch population and the generalization of results needs caution. The small group of participants with diabetes or CKD and CAC data also limits the power for statistical inference. Further, we were not able to rule out influences from survival selection and were only able to investigate the association of SAF with a history of non-fatal MI as the clinical outcome of fatal MI before SAF measurement was automatically precluded. Nevertheless, in both cases, selection would likely have biased the associations toward the null. In addition, reverse causation might have biased the estimations because some outcomes were assessed before SAF measurement although SAF showed a slow yearly progression [