Elevated lipoprotein(a) and cardiovascular outcomes in prediabetes and diabetes: a systematic review and meta-analysis

Background: Elevated levels of lipoprotein(a) [Lp(a)] and diabetes have been identified as potential risk factors for coronary artery disease (CAD). This study investigates various Lp(a) levels' impact on atherosclerotic cardiovascular disease (ASCVD) events in pre-diabetics and diabetics. Methods: We included retrospective studies in English until May 2023, exploring the link between high Lp(a) levels and cardiovascular outcomes in humans with diabetes, prediabetes, or normal glucose levels. Studies were sourced from PubMed, Scopus, and Google Scholar, emphasizing detailed population and outcome data. We excluded studies with major methodological issues, low-quality data, missing key information, duplicates, and non-human subjects. We included high-quality retrospective studies on Lp(a) and cardiovascular outcomes, using risk of bias tools like Newcastle-Ottawa Scale (NOS) to ensure data integrity, and resolved discrepancies through discussion. Binary random-effects models were employed to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Leave one out sensitivity analysis was performed. Heterogeneity was assessed using I2 statistics. For outcomes showing moderate or high heterogeneity, subgroup analyses were performed for follow-up duration or type of study. Results: A total of 20,271 patients with diabetes, prediabetes, and non-diabetics were included from three studies. In our analysis, compared to non-diabetics with Lp(a) <10 mg/dL, the risk of ASCVD increased with an increase in Lp(a) levels among pre-diabetics [Lp(a) <10 mg/dL (HR: 1.40, 95% CI: 1.17-1.67), Lp(a) 10- 30 mg/dL (HR: 1.60, 95% CI: 1.30-1.96), Lp(a) >30 mg/dL (HR: 2.08, 95% CI: 1.49-2.90)] and diabetics [Lp(a) <10 mg/dL (HR: 2.42, 95% CI: 1.97-2.98), Lp(a) 10-30 mg/dL (HR: 2.26, 95% CI: 1.64-3.12), Lp(a) >30 mg/dL (HR: 4.17, 95% CI: 3.24-5.37)] with statistical significance (P<0.01). Conclusions: High Lp(a) (>30 mg/dL) is associated with more ASCVD events in diabetics and prediabetics vs. Lp(a) <30 mg/dL, underscoring Lp(a)'s clinical importance in risk stratification and intervention.