Association of lipoprotein a with myocardial performance, coronary flow and endothelial function in individuals without overt cardiovascular disease

Background

Lipoprotein(a) (Lp(a)) is a genetically determined low-density lipoprotein bound to apolipoprotein(a). Elevated levels are implicated in the development of cardiovascular disease (CVD).

Purpose

We investigated the association of Lp(a) levels with markers of myocardial performance, work , coronary flow and endothelial glycocalyx integrity and their change through six-month follow-up.

Methods

We included individuals without overt CVD. We recorded a comprehensive medical history and measured Lp(a) levels via using a dedicated kit. All participants’ treatments were amended for strict management of their cardiovascular risk factors. We measured at baseline and at 6-month follow-up: a) Perfused Boundary Region of sublingual microvessels with diameter range 4 to 25 μμ (PBR) as a metric of endothelial glycocalyx integrity and flow mediated dilation (FMD) in brachial artery to assess endothelial function, b) Left Ventricular Global Longitudinal Strain (LV GLS) to assess myocardial performance by speckle tracking echocardiography, c) Global Work Index, Global Constructive Work, Global Wasted Work, Global Work Efficiency derived in pressure-volume loops via echocardiography and d) Coronary Flow Reserve (CFR) via adenosine in echocardiography to assess coronary flow in Left Anterior Descending Artery. We also recruited individuals with Lp(a) levels with similar age and sex as control group and performed only baseline evaluation.

Results

We totally enrolled n=112 participants, aged 54±11 years, 56/112 (50%) males and n=50 individuals in control group. The mean Lp(a) values were 270.34±68.45 nmol/l. 45/112 (40%) had hyperlipidemia, 19/112 (17%) diabetes, 38/112 (24%) hypertension and 47/112 (42%) were active smokers. Participants with increased Lp(a) values displayed more impaired PBR, LV GLS, GWE, GCW, GWW, CFR and FMD than controls (Table, p<0.05). Lp(a) values were associated with baseline PBR (r:0.545, p=0.016), LVGLS (r:0.252, p=0.038), GWE (r:-0.300, p=0.026), GCW (r:-0.176, p=0.046), GWW (r:0.264, p=0.035), CFR (r:-0.241, p=0.021) and FMD (r:-0.235, p=0.031) respectively.

At 6 months follow-up, after intensive treatment of all CV factors, we observed significant improvement of CFR (2.30±0.29 vs 2.45±0.30, p=0.022), LVGLS (-19.07±2.21% vs -20.10±2.35%, p=0.036) and GWE (92.40±4.97% vs 94.50±2.87%, p=0.040). Of note, higher baseline Lpa values were associated with less improvement of CFR (r:-0.688, p=0.001), GLS (r:-0.321, p=0.028) and GWE (r:-0.378, p=0.020) respectively.

Conclusion

Lpa values are associated with markers of endothelial function, myocardial performance and coronary flow through 6-month assessment in individuals without established CVD after intensivetreatment of all CV factors.TABLE