Increased Serum Lipoprotein(a) Concentrations and Low Molecular Weight Phenotypes of Apolipoprotein(a) Are Associated with Symptomatic Peripheral Arterial Disease

Abstract Background: Increased concentrations of lipoprotein(a) [Lp(a)] have been considered a genetically determined risk factor for coronary artery and cerebrovascular disease. Only 2 small and conflicting studies have investigated the possibility of an association of peripheral arterial disease (PAD) with high serum Lp(a) concentrations and low molecular weight (LMW) phenotypes of apolipoprotein(a) [apo(a)]. Methods: We measured serum concentrations of Lp(a) and apo(a) phenotypes in 213 patients with symptomatic PAD and 213 controls matched for sex, age (within 2 years), and presence of diabetes. Results: Patients with PAD showed significantly higher median serum concentrations of Lp(a) (76 vs 47 mg/L; P = 0.003) and a higher frequency of LMW apo(a) phenotypes (41% vs 26%; P = 0.002) than controls. After adjustment for several potential confounders, increased Lp(a) concentrations (>195 mg/L, i.e., 75th percentile of the entire study sample) and LMW apo(a) phenotypes were significant predictors of PAD, with odds ratios of 3.73 (95% CI 2.08–6.67; P <0.001) and 2.21 (95% CI 1.33–3.67; P = 0.002), respectively. Conclusions: In this study sample, both increased serum concentrations of Lp(a) and the presence of LMW apo(a) phenotypes were associated with the presence of symptomatic PAD independent of traditional and nontraditional cardiovascular risk factors. Because PAD is considered an indicator of systemic atherosclerotic disease, our results suggest a possible role of Lp(a) as a genetically determined marker for systemic atherosclerosis.

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Lipoprotein (a) concentrations, apolipoprotein (a) phenotypes, and peripheral arterial disease in three independent cohorts

Cardiovascular Research ◽

10.1093/cvr/cvu107 ◽

2014 ◽

Vol 103 (1) ◽

pp. 28-36 ◽

Cited By ~ 49

Author(s):

A. Laschkolnig ◽

B. Kollerits ◽

C. Lamina ◽

C. Meisinger ◽

B. Rantner ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Arterial Disease ◽

Lipoprotein A ◽

Apolipoprotein A ◽

Peripheral Arterial

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Extremely elevated lipoprotein (a) as an independent risk factor for peripheral arterial disease in large patient cohort

European Heart Journal ◽

10.1093/ehjci/ehaa946.2397 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M.R Poudel ◽

S Kirana ◽

D Stoyanova ◽

K.P Mellwig ◽

D Hinse ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Arterial Disease ◽

P Value ◽

Lipoprotein A ◽

Large Patient ◽

Increased Risk ◽

Revascularization Therapy ◽

Peripheral Arterial

Abstract Background Elevated lipoprotein (a) [LP (a)] levels are an independent, genetic, and causal factor for cardiovascular disease and associated with myocardial infarction (MI). Although the association between circulating levels of lipoprotein(a) [Lp(a)] and risk of coronary artery disease (CAD) is well established, its role in risk of peripheral arterial disease (PAD) remains unclear. PAD affects over 236 million individuals and follows ischaemic heart disease (IHD) and cerebrovascular disease (CVD) as the third leading cause of atherosclerotic cardiovascular morbidity worldwide. LP (a) is genetically determined, stable throughout life and yet refractory to drug therapy. While 30 mg/dl is considered the upper normal value for LP (a) in central Europe, extremely high LP (a) levels (>150mg/dl) are rare in the general population. The aim of our study was to analyse the correlation between lipoprotein (a) [LP (a)] levels and an incidence of PAD in high-risk patients. Patients and methods We reviewed the LP (a) concentrations of 52.898 consecutive patients admitted to our cardiovascular center between January 2004 and December 2014. Of these, 579 patients had LP (a) levels above 150 mg/dl (mean 181.45±33.1mg/dl). In the control collective LP (a) was <30mg/dl (n=350). Other atherogenic risk factors in this group were HbA1c 6.58±1.65%, low density lipoprotein (LDL) 141.99±43.76 mg/dl, and body mass index 27.81±5.61. 54.40% were male, 26.07% were smokers, 93.2% had hypertension, and 24% had a family history of cardiovascular diseases. More than 82.6% were under statins. The mean glomerular filtration rate (GFR) was 69.13±24.8 ml/min [MDRD (Modification of Diet in Renal Disease)]. Results 45.00% (n=261) of the patients with LP (a) >150mg/dl had PAD. The prevalence of PAD in patients with LP (a) <30mg/dl in our control collective was 15.8%. (P- Value 0.001). Patients with LP (a) >150mg/dl had a significantly increased risk for PAD (Odds ratio 4.36, 95% CI 2.94–6.72, p: 0.001). 19.1% of patients were re-vascularized by percutaneous angioplasty (PTA) and 7.09% of patients had to undergo peripheral vascular bypass (PVB). Mean LP (a) level in patients with PAD was 182.6±31.61. Conclusion Elevated LP (a) levels above 150 mg/dl are associated with a significantly increased risk of PAD in our collective and it confirms our hypothesis. Over one fourth of these patients had severe PAD and requiring revascularization therapy. We need more prospective studies to confirm our findings. Funding Acknowledgement Type of funding source: None

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Lipoprotein(a) as a unique primary risk factor for early atherosclerotic peripheral arterial disease

BMJ Case Reports ◽

10.1136/bcr-2021-243231 ◽

2021 ◽

Vol 14 (6) ◽

pp. e243231

Author(s):

John Mayo ◽

Thomas Hoffman ◽

Ryan Smith ◽

Dwight Kellicut

Keyword(s):

Risk Factor ◽

Cardiovascular Diseases ◽

Peripheral Arterial Disease ◽

Arterial Disease ◽

Common Condition ◽

Elevated Plasma ◽

Early Screening ◽

Lipoprotein A ◽

Peripheral Arterial ◽

Primary Risk Factor

Elevated plasma lipoprotein(a) is a relatively common condition that contributes to many cardiovascular diseases. However, the awareness and testing for this condition remain low. Herein, we present a case of an otherwise healthy and active man who developed symptoms of peripheral arterial disease starting at age 49, and was found to have hyper-lipoprotein(a) as his only notable risk factor. Diagnosis was not made until years later, after an extensive workup. Upon further screening, he was also found to have subclinical coronary and carotid artery atherosclerotic disease. The patient was treated with aspirin, statin, niacin and angioplasty to bilateral superficial femoral arteries with good symptom resolution. Early screening of his son also revealed a similarly elevated lipoprotein(a) level. It is important to raise awareness of this condition and its relationship to early-onset peripheral arterial disease so patients and their families can be appropriately identified, counselled and treated.

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