Elsevier

Atherosclerosis

Volume 282, March 2019, Pages 52-56
Atherosclerosis

Lipoprotein(a) levels and risk of cardiovascular disease events in individuals with diabetes mellitus or prediabetes: The Atherosclerosis Risk in Communities study

https://doi.org/10.1016/j.atherosclerosis.2018.12.022Get rights and content

Highlights

  • Incident ASCVD rates were higher in adults with diabetes/prediabetes than without.

  • Whites with diabetes/prediabetes and elevated Lp(a) had even greater ASCVD risk.

  • Adding Lp(a) to traditional risk factors improved ASCVD risk prediction.

  • Measuring Lp(a) may benefit ASCVD risk stratification in diabetes/prediabetes.

Abstract

Background and aims

Diabetes increases risk for atherosclerotic cardiovascular disease (ASCVD). Current guidelines do not recommend measuring lipoprotein(a), another ASCVD risk factor, in these individuals. We examined the association of lipoprotein(a) levels with incident ASCVD events in persons with and without diabetes or prediabetes.

Methods

Lipoprotein(a) and other ASCVD risk factors were measured at baseline (1996–1998) in the biracial Atherosclerosis Risk in Communities study; participants without prevalent ASCVD (coronary heart disease or stroke) were monitored ∼15 years for incident ASCVD events.

Results

Of 9871 eligible participants (mean age 63 years; 5816 women; 2155 African Americans), 1543 had diabetes and 3615 had prediabetes. Cumulative ASCVD incidence rates (event/1000-person years) were higher in participants with diabetes (26%) or prediabetes (13%) than in nondiabetic individuals (10%, p < 0.001). When comparing highest to lowest lipoprotein(a) categories (≥50 mg/dL vs. ≤10 mg/dL), increasing lipoprotein(a) levels were significantly associated with increasing incident ASCVD events in Caucasian participants with prediabetes (hazard ratio [HR] = 1.35; 95% confidence interval [CI] 1.07–1.69); p = 0.03) and diabetes (HR = 1.42; 95% CI 1.10–1.84; p < 0.01), but not those with normal fasting blood glucose. Adding lipoprotein(a) to Pooled Cohort Equation variables improved risk prediction in persons with diabetes (Δ in area under the receiver operating characteristic curve [AUC] 0.0087, net reclassification index [NRI] 0.1761) and prediabetes (ΔAUC 0.0025, NRI 0.0938).

Conclusions

In this biracial cohort, elevated lipoprotein(a) levels in Caucasian individuals with diabetes or prediabetes were associated with further increased ASCVD risk. Adding lipoprotein(a) to traditional risk factors improved ASCVD risk prediction.

Introduction

Prospective studies and Mendelian randomization data have shown that lipoprotein(a) [Lp(a)] is associated with incidence of atherosclerotic cardiovascular disease (ASCVD) [[1], [2], [3], [4]]. Individuals with diabetes mellitus also have high risk for incident ASCVD events [5]. The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelines recommend moderate- or high-intensity statin therapy based on 10-year ASCVD risk in patients with diabetes aged 40–75 years for primary prevention [6]. A recent meta-analysis by Waldeyer et al. showed a robust association of elevated Lp(a) and ASCVD events in a European cohort, particularly among those with diabetes [7]. The ACC/AHA guidelines do not recommend measurement of Lp(a) for high-risk individuals such as those with diabetes or prediabetes for ASCVD risk stratification [6]. Lp(a) measurement may be of particular interest in African Americans, who have higher risk for prediabetes and diabetes as well as higher Lp(a) levels compared with Caucasians [8].

We evaluated the association between Lp(a) and ASCVD events by diabetes status (no diabetes, prediabetes, or diabetes) in African American and Caucasian adults in the Atherosclerosis Risk in Communities (ARIC) Study. We hypothesized that measurement of Lp(a) would improve risk prediction of ASCVD events, particularly in those with prediabetes or diabetes.

Section snippets

Study population

The ARIC study is a prospective study of cardiovascular disease incidence in 15,792 men and women recruited from four US communities [9]. The current analyses included 9871 individuals who had Lp(a) measured at ARIC visit 4 (1996–1998) and did not have prevalent ASCVD at that time (Supplemental Fig. 1). Participants were categorized by glycemic status. Diabetes was defined as a fasting plasma glucose level ≥126 mg/dL, a nonfasting plasma glucose level ≥200 mg/dL, or a self-reported history of

Results

Over a median (25th, 75th percentile) follow-up of 15.6 (11.3, 16.6) years, the 10-year absolute risk for ASCVD events was 23% in persons with diabetes, 13% in persons with prediabetes, and 9% in persons with normal FBG (Table 1). Approximately 34% (n = 520) of diabetic persons and 29% (n = 1049) of prediabetic persons had an Lp(a) level >30 mg/dL; of these, 15% (n = 76) of diabetic persons and 11% (n = 115) of prediabetic persons were on statins, and 60% (n = 310) of diabetic persons and 53%

Discussion

Our results show that diabetic and prediabetic individuals with higher Lp(a) levels had higher rates of incident ASCVD events in this biracial cohort of Americans. When stratified by race, this association was significant only in Caucasian and not in African American participants. In the overall cohort, the addition of Lp(a) to the PCE variables improved ASCVD risk prediction.

Similar findings were shown in an analysis of European individuals with diabetes from the Biomarkers for Cardiovascular

Conflicts of interest

Dr. Hoogeveen has received grant support from Denka Seiken Co., Ltd. Denka Seiken Co., Ltd. played no role in design, data analysis, or data interpretation for this study. The other authors have nothing to disclose.

Financial support

The Atherosclerosis Risk in Communities study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under contract nos. HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I); ES. was supported by R01-DK089174; CMB. was supported by R01-HL134320.

Author contributions

Anum Saeed: Conception and design of study question, data interpretation, literature search, manuscript drafting with revision, and correspondence with coauthors for critical review of scientific content.

Wensheng Sun: Analysis of data.

Anandita Agarwala: Critical revision of manuscript for intellectual and scientific content.

Salim S. Virani: Critical revision of manuscript for intellectual and scientific content.

Vijay Nambi: Critical revision of manuscript for intellectual and scientific content.

Acknowledgments

The authors thank the ARIC participants and staff for their important contributions.

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