Relative Prognostic Importance and Optimal Levels of Risk Factors for Mortality and Cardiovascular Outcomes in Type 1 Diabetes Mellitus

Abstract

Background: The strength of association and optimal levels for risk factors related to excess risk of death and cardiovascular outcomes in type 1 diabetes mellitus have been sparsely studied. Methods: In a national observational cohort study from the Swedish National Diabetes Register from 1998 to 2014, we assessed relative prognostic importance of 17 risk factors for death and cardiovascular outcomes in individuals with type 1 diabetes mellitus. We used Cox regression and machine learning analyses. In addition, we examined optimal cut point levels for glycohemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol. Patients with type 1 diabetes mellitus were followed up until death or study end on December 31, 2013. The primary outcomes were death resulting from all causes, fatal/nonfatal acute myocardial infarction, fatal/nonfatal stroke, and hospitalization for heart failure. Results: Of 32 611 patients with type 1 diabetes mellitus, 1809 (5.5%) died during follow-up over 10.4 years. The strongest predictors for death and cardiovascular outcomes were glycohemoglobin, albuminuria, duration of diabetes mellitus, systolic blood pressure, and low-density lipoprotein cholesterol. Glycohemoglobin displayed ≈2% higher risk for each 1-mmol/mol increase (equating to ≈22% per 1% glycohemoglobin difference), whereas low-density lipoprotein cholesterol was associated with 35% to 50% greater risk for each 1-mmol/L increase. Microalbuminuria or macroalbuminuria was associated with 2 to 4 times greater risk for cardiovascular complications and death. Glycohemoglobin <53 mmol/mol (7.0%), systolic blood pressure <140 mm Hg, and low-density lipoprotein cholesterol <2.5 mmol/L were associated with significantly lower risk for outcomes observed. Conclusions: Glycohemoglobin, albuminuria, duration of diabetes mellitus, systolic blood pressure, and low-density lipoprotein cholesterol appear to be the most important predictors for mortality and cardiovascular outcomes in patients with type 1 diabetes mellitus. Lower levels for glycohemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than contemporary guideline target levels appear to be associated with significantly lower risk for outcomes.

Resistant Hypertension and Risk of Adverse Events in Individuals With Type 1 Diabetes: A Nationwide Prospective Study

“…Notably, we found that those with normal AER and microalbuminuria with RH had 3.5 times higher risk of stroke, compared with those who had controlled BP. It is well known that hypertension is one of the strongest risk factors for stroke, both in the general population (35) and in type 1 diabetes (19, 36). The risk of stroke increases after BP exceeds 130/80 mmHg in individuals with type 2 diabetes (37), while among individuals with type 1 diabetes a linear increase in systolic BP is observed even earlier (19).…”

Mesa 1: Diabetes mellitus tipo 1 y enfermedad cardiovascular

“…La duración de la diabetes es uno de los predictores más importantes para infarto agudo de miocardio (IAM), junto con el colesterol de lipoproteínas de baja densidad (cLDL) y HbA1c. El desarrollo de DM1 antes de los 10 años de edad se asocia con un riesgo 90 veces mayor de IAM en mujeres y 30 veces mayor de ECV hacia los primeros años de su vida adulta generando una pérdida de años de vida de 17,7 y 14,2 en mujeres y hombres con DM1 respectivamente 8,9,10,11 (Figura 1).…”

“…La HbA1c y la albuminuria son los predictores más importantes de mortalidad y ECV. La duración de la diabetes, la albuminuria y la PAS tienen interacciones estadísticamente significativas con HbA1c 9,10,11 . 1) Control glucémico.…”

“…La HbA1c se relaciona más fuertemente con eventos cardiovasculares fatales que no fatales, aún con HbA1c ≤6,9%. Existe un 2% de aumento de RR de mortalidad cardiovascular para cada aumento de mmol/mol de HbA1c (HR=1.02; IC95%, 1,017-1,023) o ~23% por cada 1% de diferencia de HbA1c 9,10,11 .…”

Enfermedad cardiovascular y diabetes

“…La principal causa de muerte en personas con DM1 es de origen cardiovascular. Si bien la mortalidad en personas con DM1 disminuyó significativamente en los últimos 40 años debido al mejor manejo de factores glucémicos y no glucémicos, el riesgo de muerte por todas las causas y cardiovascular en DM1 con inadecuado control glucémico es ocho a 10 veces mayor que en la población general 7,8,9 . El primer evento cardiovascular (CV) en DM1 ocurre en promedio 10 a 15 años antes que en personas sin DM 10 .…”