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

Saeed, Anum; Sun, Wei; Agarwala, Anandita; Virani, Salim S.; Nambi, Vijay; Coresh, Josef; Selvin, Elizabeth; Boerwinkle, Eric; Jones, Peter H.; Ballantyne, Christie M.; Hoogeveen, Ron C.

doi:10.1016/j.atherosclerosis.2018.12.022

Cited by 56 publications

(31 citation statements)

References 24 publications

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“…Intriguingly, both the present study and our previous analysis (24) observed that T2D patients tended to have a lower Lp(a) level, indicating an inverse association between Lp (a) concentrations and T2D. Nevertheless, previous studies suggested that diabetes status did not attenuate the robust association between Lp (a) and cardiovascular risk (9,29), and high glucose metabolism status plus elevated Lp (a) levels even had a higher risk for cardiovascular events (30). In the current analysis, we similarly found that the association between Lp (a) concentrations and reduced renal function risk was more prominent in patients with T2D or hypertension.…”

Section: Discussionsupporting

confidence: 49%

Serum lipoprotein (a) associates with a higher risk of reduced renal function: a prospective investigation

Luo

Wang

Dai

et al. 2020

Journal of Lipid Research

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Lipoprotein (a) (Lp [a]) is a well-known risk factor for cardiovascular disease, but analysis on Lp (a) and renal dysfunction is scarce. We aimed to investigate prospectively the association of serum Lp (a) with the risk of reduced renal function, and further investigated whether diabetic or hypertensive status modified such association. 6,257 Chinese adults aged ≥40 years and free of reduced renal function at baseline were included in the study. Reduced renal function was defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. During a mean follow-up of 4.4 years, 158 participants developed reduced renal function. Each 1-unit increase in log10-Lp (a) (mg/dl) was associated with 1.99-folds (95% confidence interval [CI] 1.15-3.43) increased risk of incident reduced renal function; multivariable-adjusted odds ratio (OR) for the highest tertile of Lp (a) was 1.61 (95% CI 1.03–2.52) compared to the lowest tertile (P for trend=0.03). The stratified analysis showed the association of serum Lp (a) and incident reduced renal function was more prominent in participants with prevalent diabetes (OR 4.04, 95% CI [1.42-11.54]) or hypertension (OR 2.18, 95% CI [1.22-3.89]). A stronger association was observed among group with diabetes and high Lp (a) (>25 mg/dl), indicating a combined effect of diabetes and high Lp (a) on the reduced renal function risk. Elevated Lp (a) level was independently associated with risk of incident reduced renal function, especially in diabetic or hypertensive patients.

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Section: Discussionsupporting

confidence: 49%

Serum lipoprotein (a) associates with a higher risk of reduced renal function: a prospective investigation

Luo

Wang

Dai

et al. 2020

Journal of Lipid Research

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“…Close attention to Lp(a), a particle containing of a low-density lipoprotein (LDL)-like particle bound to apolipoprotein(a), has emergingly been paid due to its pathogenic role in atherosclerosis and thrombosis formation [ 6 ]. Epidemiological and prospective data have suggested that a high level of Lp(a) is an independent risk factor for incident cardiovascular disease (CVD) [ 7 , 8 ], particularly among those with DM [ 9 , 10 ]. Simultaneously, in the secondary prevention setting, elevated Lp(a) values were also proved to be an independent predictor of CVEs in patients with established coronary artery disease (CAD) [ 11 ] or patients undergone percutaneous coronary intervention (PCI) [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Lipoprotein (a) predicts recurrent worse outcomes in type 2 diabetes mellitus patients with prior cardiovascular events: a prospective, observational cohort study

Zhang

Jin

Cao

et al. 2020

Cardiovasc Diabetol

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Background: Merging studies have reported the association of lipoprotein(a) [Lp(a)] with poor outcomes of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, the prognostic importance of Lp(a) for recurrent cardiovascular events (CVEs) is currently undetermined in patients with T2DM and prior CVEs. Methods: From April 2011 to March 2017, we consecutively recruited 2284 T2DM patients with prior CVEs. Patients were categorized into low, medium, and high groups by Lp(a) levels and followed up for recurrent CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Kaplan-Meier, Cox regression and C-statistic analyses were performed. Results: During 7613 patient-years' follow-up, 153 recurrent CVEs occurred. Lp(a) levels were significantly higher in patients with recurrent CVEs than counterparts (20.44 vs. 14.71 mg/dL, p = 0.002). Kaplan-Meier analysis revealed that the event-free survival rate was dramatically lower in high and medium Lp(a) groups than that in low group irrespective of HBA1c status (< 7.0%; ≥ 7.0%, both p < 0.05). Furthermore, multivariate Cox regression models indicated that Lp(a) was independently associated with high risk of recurrent CVEs [HR(95% CI): 2.049 (1.308-3.212)], such data remains in different HBA1c status (HR(95% CI): < 7.0%, 2.009 (1.051-3.840); ≥ 7.0%, 2.162 (1.148-4.073)). Moreover, the results of C-statistic were significantly improved by 0.029 when added Lp(a) to the Cox model. Conclusions: Our data, for the first time, confirmed that Lp(a) was an independent predictor for recurrent CVEs in T2DM patients with prior CVEs, suggesting that Lp(a) measurement may help to further risk stratification for T2DM patients after they suffered a first CVE.

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“…These guidelines also recommend lipid targets for T2DM patients as LDL-C ,1.8 mmol/L and non-HDL cholesterol (non-HDL-C) ,2.6 mmol/L, which is the same as for patients with established coronary artery disease (CAD) (10,11). Although patients with T2DM did not exhibit higher levels of Lp(a), results from the Biomarker for Cardiovascular Risk Assessment across Europe (BiomarCaRE) consortium indicated that elevated Lp(a) was robustly associated with an increased risk for first ever CVD in individuals with diabetes mellitus (DM) (12,13). Pre-diabetes mellitus (pre-DM) is an intermediate state between normal glucose regulation (NGR) and DM, with a 35.7% morbidity rate in China (14).…”

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confidence: 99%

“…Pre-diabetes mellitus (pre-DM) is an intermediate state between normal glucose regulation (NGR) and DM, with a 35.7% morbidity rate in China (14). Recently, Saeed et al (12) reported that elevated Lp(a) levels in Caucasian individuals with DM or pre-DM were positively related to CVD risk in a primary prevention study. Our previous studies suggested that Lp(a) levels were strongly associated with the presence and severity of stable CAD in individuals with DM and patients with familial hypercholesterolemia (15,16).…”

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confidence: 99%

Lipoprotein(a) and Cardiovascular Outcomes in Patients With Coronary Artery Disease and Prediabetes or Diabetes

et al. 2019

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The aim of the current study is to determine the impact of elevated lipoprotein(a) [Lp(a)] on cardiovascular events (CVEs) in stable coronary artery disease (CAD) patients with different glucose metabolism status. RESEARCH DESIGN AND METHODS In this multicenter study, we consecutively enrolled 5,143 patients from March 2011 to February 2015. Patients were categorized according to status of glucose metabolism (diabetes mellitus [DM], pre-diabetes mellitus [pre-DM], and normal glucose regulation [NGR]) levels and further classified into 12 groups by Lp(a) levels. CVE end points included nonfatal acute myocardial infarction (MI), stroke, and cardiovascular mortality. All subjects were followed up for the occurrence of the CVEs. RESULTS During a median of 6.1 years' follow-up, 435 (8.5%) CVEs occurred. No significant difference in occurrence of CVEs was observed between NGR and pre-DM groups (hazard ratio 1.131 [95% CI 0.822-1.556], P > 0.05). When status of glucose metabolism was incorporated in stratifying factors, 30 £ Lp(a) < 50 mg/dL and Lp(a) ‡50 mg/dL were associated with significantly higher risk of subsequent CVEs in pre-DM (2.181 [1.099-4.327] and 2.668 [1.383-5.415], respectively; all P < 0.05) and DM (3.088 [1.535-5.895] and 3.470 [1.801-6.686], all P < 0.05). Moreover, adding Lp(a) to the Cox model increased the C-statistic by 0.022 and 0.029 in pre-DM and DM, respectively, while the C-statistic was not statistically improved when Lp(a) was included for CVEs prediction in NGR. CONCLUSIONS Our findings, for the first time, indicated that elevated Lp(a) levels might affect the prognosis in patients with pre-DM with stable CAD, suggesting that Lp(a) may help further stratify stable CAD patients with mild impaired glucose metabolism. Lipoprotein(a) [Lp(a)] is an LDL-like particle consisting of a moiety of apolipoprotein(a) bounding covalently to apolipoprotein B-100 (1,2). Plasma Lp(a) induces proatherogenic effects via LDL moiety and prothrombotic effects by the plasminogen-like apolipoprotein(a) (3,4). Strong evidence in epidemiological, genetic, and prospective cohort studies verified that circulating Lp(a) levels were associated with the presence of cardiovascular disease (CVD) (5-7). In the Atherothrombosis

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

Cited by 56 publications

References 24 publications

Serum lipoprotein (a) associates with a higher risk of reduced renal function: a prospective investigation

Serum lipoprotein (a) associates with a higher risk of reduced renal function: a prospective investigation

Lipoprotein (a) predicts recurrent worse outcomes in type 2 diabetes mellitus patients with prior cardiovascular events: a prospective, observational cohort study

Lipoprotein(a) and Cardiovascular Outcomes in Patients With Coronary Artery Disease and Prediabetes or Diabetes

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