A recent Mayo Clinic study has revealed a major gap in current genetic screening practices, warning that standard testing guidelines fail to identify the vast majority of people with familial hypercholesterolemia (FH) — a hereditary condition that causes dangerously high cholesterol levels from birth and significantly raises the risk of early heart disease.
The study found that nearly 90% of individuals carrying FH-linked genetic mutations would have been overlooked under existing screening protocols, which typically rely on cholesterol levels and family medical history. As a result, many people remain unaware of their condition until they suffer serious cardiovascular complications such as heart attacks or strokes.
FH is often passed silently across generations. While treatments including statins, PCSK9 inhibitors, and lifestyle modifications can dramatically reduce cardiovascular risk, delayed or missed diagnosis leaves undetected carriers vulnerable to life-threatening events.
Why FH Is a Growing Public Health Concern
In the United States, cardiovascular diseases remain among the leading causes of death, claiming nearly 700,000 lives annually, according to the Centers for Disease Control and Prevention (CDC). High levels of low-density lipoprotein (LDL) cholesterol are a key contributor, and FH dramatically amplifies this danger.
Adults with FH frequently have LDL levels exceeding 190 mg/dL, while affected children may show even higher levels, leading to early plaque buildup in arteries.
Globally, the burden is equally severe. According to the World Health Organisation (WHO), cardiovascular diseases accounted for 19.8 million deaths in 2022, representing 32% of all global deaths. Of the 18 million premature deaths from non-communicable diseases in 2021, 38% were caused by cardiovascular conditions.
Key Findings From the Mayo Clinic Study
The research, published in Circulation: Genomic and Precision Medicine, analysed data from over 84,000 participants enrolled in Mayo Clinic’s Tapestry DNA initiative across its Arizona, Florida and Minnesota campuses.
Using exome sequencing — a technique that examines protein-coding regions responsible for over 85% of known disease-causing mutations — researchers identified 419 individuals with pathogenic FH variants.
Key findings include:
- Nearly 75% of those identified would not have qualified for genetic testing under current guidelines
- About one in five had already developed coronary artery disease before their diagnosis
- Many carriers had only moderately elevated LDL levels, making them easy to miss through routine blood tests
Experts Call for Broader Genetic Screening
Dr Niloy Jewel Samadder, the study’s lead author and a gastroenterologist and cancer geneticist at the Mayo Clinic Comprehensive Cancer Center, said the findings expose a critical blind spot in national screening guidelines.
“Our findings reveal a major gap in current guidelines, which depend heavily on cholesterol levels and family history,” Samadder said. “If we can identify individuals at risk earlier, we can intervene sooner, alter disease progression, and likely save lives.”
FH is one of the most common inherited genetic disorders worldwide, affecting approximately 1 in 200 to 250 people across all populations. Without treatment, men may experience heart attacks in their 40s, and women in their 50s, often decades earlier than average.
Rethinking How Genetic Testing Is Done
Dr Samadder advocates moving genetic screening out of specialised settings and into primary care, similar to routine checks for blood pressure or diabetes. Integrating genetic risk assessment with electronic health records could allow automated alerts for clinicians, enabling earlier testing and treatment.
Researchers believe expanding routine genetic screening could significantly reduce severe cardiovascular events, especially among people who otherwise appear healthy.