Familial Hypercholesterolemia and Risk of Peripheral Arterial Disease and Chronic Kidney Disease

Related Experiment Video

Updated: Feb 6, 2026

Assessment of Vascular Function in Patients With Chronic Kidney Disease

Assessment of Vascular Function in Patients With Chronic Kidney Disease

Published on: June 16, 2014

Frida Emanuelsson^1,2, Børge G Nordestgaard^2,3,4, Marianne Benn^1,2,4

¹Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

The Journal of Clinical Endocrinology and Metabolism

|August 8, 2018

Insights

Individuals with familial hypercholesterolemia (FH) have higher risks of peripheral arterial disease (PAD) and chronic kidney disease (CKD). Low ankle-brachial index (ABI) and estimated glomerular filtration rate (eGFR) indicate a greater risk of myocardial infarction.

Area of Science:

Cardiovascular Medicine
Nephrology
Genetics

Background:

Familial hypercholesterolemia (FH) significantly increases coronary artery disease risk.
The association of FH with peripheral arterial disease (PAD) and chronic kidney disease (CKD) remains unclear.

Purpose of the Study:

To investigate elevated risks of PAD and CKD in individuals with clinical FH.
To determine if low ankle-brachial index (ABI) and estimated glomerular filtration rate (eGFR) correlate with myocardial infarction risk in FH patients.

Main Methods:

Prospective cohort study involving 106,172 individuals, with 7,109 diagnosed with FH.
Analysis of associations between FH, PAD, CKD, and myocardial infarction.
Utilized multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs).

Main Results:

FH patients showed significantly higher ORs for PAD (1.84-1.36) and CKD (1.92-2.42) compared to controls.
Low ABI (≤0.9) in FH patients was associated with a 4.60-fold increased risk of myocardial infarction.
Low eGFR (<60 mL/min/1.73 m2) in FH patients correlated with a 2.19-fold increased risk of myocardial infarction.

Conclusions:

Clinical FH is linked to increased risks of PAD and CKD.
Low ABI and eGFR serve as important prognostic indicators for myocardial infarction in FH individuals.
Screening for PAD and CKD, alongside ABI and eGFR monitoring, is recommended for managing FH patients at high cardiovascular risk.

Read full analysis

Abstract

Context:

Individuals with familial hypercholesterolemia (FH) have a high risk of coronary artery disease, but their risk of peripheral arterial disease (PAD) and chronic kidney disease (CKD) is unknown.

Objective:

In individuals with clinical FH, we tested the hypotheses (1) that the risks of PAD and CKD are elevated and (2) that low ankle-brachial index (ABI) and estimated glomerular filtration rate (eGFR) are associated with a high risk of myocardial infarction.

Design And Setting:

Prospective cohort study of the general population.

Participants:

A total of 106,172 individuals, of whom 7109 were diagnosed with FH.

Main Outcome Measures:

PAD, CKD, and myocardial infarction.

Results:

Compared with individuals with unlikely FH, multivariable adjusted ORs (95% CIs) of PAD were 1.84 (1.70 to 2.00) in those with possible FH and 1.36 (1.00 to 1.84) in individuals with probable/definite FH. For CKD, the corresponding ORs (95% CIs) were 1.92 (1.78 to 2.07) and 2.42 (1.86 to 3.26). Compared with individuals with unlikely FH and ABI >0.9, the multivariable adjusted hazard ratio (95% CI) of myocardial infarction was 4.60 (2.36 to 8.97) in those with possible/probable/definite FH and ABI ≤0.9. Compared with individuals with unlikely FH and eGFR ≥60 mL/min/1.73 m2, the corresponding value was 2.19 (1.71 to 2.82) in those with possible/probable/definite FH and eGFR <60 mL/min/1.73 m2.

Conclusions:

Individuals with clinical FH have increased risks of PAD and CKD, and low ABI and eGFR are associated with high risk of myocardial infarction. Consequently, individuals with FH should be screened for PAD and CKD, and ABI and eGFR may be used as prognostic tools in the management and treatment of FH to identify those at very high risk of myocardial infarction.

More Related Videos

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes

Published on: September 15, 2018

Reduction of Radiation Exposure during Endovascular Treatment of Peripheral Arterial Disease Combining Fiber Optic RealShape Technology and Intravascular Ultrasound

Reduction of Radiation Exposure during Endovascular Treatment of Peripheral Arterial Disease Combining Fiber Optic RealShape Technology and Intravascular Ultrasound

Published on: April 21, 2023

Related Concept Videos

Chronic Kidney Disease I: Introduction

Chronic Kidney Disease I: Introduction

Chronic Kidney Disease (CKD) arises when the kidneys progressively lose their ability to function, ultimately leading to end-stage renal disease. At this advanced stage, the kidneys can no longer filter waste or maintain essential body functions, requiring renal replacement therapy (RRT) through dialysis or a kidney transplant for survival.Early-stage chronic kidney disease and detection challengesIn CKD's early stages, symptoms often remain absent because healthy nephrons compensate for...

Peripheral Artery Disease I: Introduction

Peripheral Artery Disease I: Introduction

Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs, particularly the arteries supplying the thighs and calves. In rare cases, it may involve other arteries, including those in the arms.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty...

Chronic Kidney Disease II: Clinical Manifestations

Chronic Kidney Disease II: Clinical Manifestations

Chronic Kidney Disease (CKD) progressively impairs multiple body systems due to the accumulation of uremic toxins, which disrupt cellular functions across various organs.Neurologic symptomsNeurologic symptoms often arise early in CKD, as uremic toxin buildup drives changes in cognitive and motor functions. Patients frequently experience fatigue, headache, confusion, difficulty concentrating, and, in severe cases, seizures. Peripheral neuropathy commonly manifests as burning sensations in the...

Chronic Kidney Disease III: Interprofessional Care

Chronic Kidney Disease III: Interprofessional Care

Chronic kidney disease (CKD) requires collaborative and comprehensive management. CKD progresses through stages and can lead to end-stage kidney disease (ESKD) if untreated. Interprofessional collaboration and patient education are crucial, enabling patients to manage their health and improve their quality of life.Diagnostic approach for chronic kidney diseaseThe diagnosis of CKD primarily focuses on the glomerular filtration rate (GFR), which assesses kidney function by measuring how well...

Chronic Kidney Disease IV: Nursing Management

Chronic Kidney Disease IV: Nursing Management

Nursing management is essential for preventing complications, maintaining stability, and improving patients' quality of life in chronic kidney disease (CKD). By using a structured approach, nurses help slow CKD progression and support effective patient care.1. Comprehensive patient assessmentEffective management begins with nurses reviewing the patient’s medical history, and identifying key risk factors like diabetes, hypertension, and nephrotoxic drug use. Nurses assess signs of...

Peripheral Artery Disease IV: Nursing Management

Peripheral Artery Disease IV: Nursing Management

The nursing management of a patient with peripheral artery disease (PAD) begins with a thorough assessment of the patient’s health history and clinical manifestations.AssessmentHealth History: Evaluate the patient’s history of hypertension, hyperlipidemia, family history of cardiovascular issues, and lifestyle factors such as dietary patterns, smoking, and physical activity.Physical Examination:Assess the affected extremity for decreased or absent peripheral pulses,...

Articles linked to this work by shared authors, journal, and citation graph.

Relationship between genetic variation at PPP1R3B and levels of liver glycogen and triglyceride.

Hepatology (Baltimore, Md.)·2017

Body mass index and breast cancer survival: a Mendelian randomization analysis.

International journal of epidemiology·2017

U-shaped relationship of HDL and risk of infectious disease: two prospective population-based cohort studies.

European heart journal·2017

Liver fat content, non-alcoholic fatty liver disease, and ischaemic heart disease: Mendelian randomization and meta-analysis of 279 013 individuals.

European heart journal·2017

Plasma urate, lung function and chronic obstructive pulmonary disease: a Mendelian randomisation study in 114 979 individuals from the general population.

Thorax·2017

Unmet need for primary prevention in individuals with hypertriglyceridaemia not eligible for statin therapy according to European Society of Cardiology/European Atherosclerosis Society guidelines: a contemporary population-based study.

European heart journal·2017

See all related articles