P655High lipoprotein(a) plasma levels is associated with higher prevalence of cardiovascular disease and poor metabolic control in patients with type 1 diabetes
Authors: Littmann K , Wodaje T , Alvarsson M , Bottai M , Parini P , Eriksson M , Brinck J 
Published: October 2019

Abstract

Background
Lipoprotein(a) [Lp(a)] is a cardiovascular risk factor that has been shown to correlate to cardiovascular disease and aortic valve disease. Plasma levels of Lp(a) has a skewed distribution, is highly influenced by genetic inheritance and is not considered to be affected by age, sex or lifestyle. Its importance for the development of vascular complications in patients with type 1 diabetes is unknown.

Purpose
To assess the contribution of Lp(a) to cardiovascular disease, microvascular complications, aortic valve disease in patients with type 1 diabetes mellitus, and to assess the relationship between diabetes metabolic control and Lp(a) levels.

Methods
We included 1857 consecutive type 1 diabetes patients receiving regular care at our out-patient clinic, department of Endocrinology, into an observational cross sectional registry study. Patient characteristics, cardiovascular history and Lp(a) measurement was extracted from their electronic medical charts. Patients were divided into four groups according to their Lp(a) levels in nmol/L (Very Low <10; Low 10–30; Intermediate 30–120; High >120) and statistical analysis was performed comparing the prevalence of mikro- and makrovascular complications between the groups. The relationship between Lp(a) and diabetes control measured as HbA1c (mmol/mol) was studied by comparing the subgroups with good (<52), average (52–70) and poor (>70) metabolic control.

Results
The mean (SD) age and diabetes duration in the cohort was 49.9 (15.8) years and 26.7 (15.5) years, respectively, and the Lp(a) median (inter quartile range) was 20.4 (7.8–75.1) nmol/L. Patients in the high Lp(a) group had significantly higher prevalence of cardiovascular and microvascular complications compared to patients with very low levels. The relative risk (confidence interval) increase to be affected by ischemic heart disease was 2.42 (1.41–4.15) (p=0.001), by albuminuria 1.87 1.26–2.78) (p=0.002) and by aortic valve disease 2.96 (1.53–5.78) (p=0.001). The relationship between Lp(a) and vascular complications was sustained when data was adjusted for age and smoking status between the groups albeit at a weaker level. No significant relationship was detected between cerebrovascular disease or the microvascular complications retinopathy and neuropathy and Lp(a) levels. Significantly higher Lp(a) levels were observed in patients with poor and average metabolic control compared to patients with good control (p<0.05). The 80:th percentile of Lp(a) was 78.6 nmol/L, 105.2 nmol/L and 100.6 nmol/L for good, average and poor metabolic control respectively (Figure 1).
Figure 1. Lp(a) levels in relation to HbA1c

Conclusions
Lp(a) is a significant risk factor for cardiovascular complications and aortic valve disease in patients with type 1 diabetes. Poor metabolic control of the diabetes disease is associated to high Lp(a) levels.

Acknowledgement/Funding
Swedish Heart Foundation (PP), The Swedish Research Council (PP), Karolinska Institutet (PP, JB), Investigator initiated study grant from Sanofi (JB)