Familial Hypercholesterolemia in Latin America: Unmet Needs, Barriers, and Challenges

Abstract

Familial hypercholesterolemia (FH) is the most common monogenic disorder predisposing individuals to premature atherosclerotic cardiovascular disease. Despite an estimated prevalence of 1 in 250 individuals, FH remains largely underdiagnosed and undertreated across Latin America, where more than 2 million people are expected to be living with FH. Early identification and intensive lipid-lowering therapy substantially improve clinical outcomes; however, multiple structural, socioeconomic, and educational barriers continue to limit optimal care throughout the region. FH detection rates remain low, and screening strategies are implemented heterogeneously: while opportunistic screening is emerging in some settings, cascade screening remains underdeveloped, with the exception of pioneering programs in Brazil and Uruguay. Real-world data from regional registries consistently demonstrate poor attainment of low-density lipoprotein cholesterol targets, partly due to the predominant use of statin monotherapy. Strengthening clinical registries, expanding access to genetic testing, implementing structured cascade screening programs, and improving availability of effective lipid-lowering therapies are essential steps to reduce the clinical and public health burden of FH in Latin America.

INTRODUCTION

Heterozygous familial hypercholesterolemia (FH) is the most common monogenic disorder predisposing individuals to premature atherosclerotic cardiovascular disease (ASCVD).¹,² It arises from pathogenic variants in genes involved in low-density lipoprotein (LDL) clearance, predominantly the LDL receptor gene (LDLR), which accounts for more than 70% of cases, and, to a lesser extent, the apolipoprotein B-100 (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes.¹ The inheritance pattern of FH is autosomal dominant, such that approximately half of the offspring of an affected individual will inherit the pathogenic variant and develop the condition.

Early and accurate diagnosis of FH is essential to altering the natural course and prognosis of the disorder. As a consequence of lifelong exposure to markedly elevated LDL cholesterol (LDL-C) levels from birth, untreated individuals with FH have a substantially increased risk of premature ASCVD.³ Real-world data consistently show that timely diagnosis combined with intensive lipid-lowering therapy significantly reduces cardiovascular events and improves long-term outcomes.⁴,⁵,⁶

With an estimated global prevalence of 1 in 250 individuals in the general population,⁷ it is expected that in Latin America, which has an approximate population of 660 million, there are about 2.4 million individuals living with FH. Among patients presenting with myocardial infarction, the prevalence of genetically confirmed FH reaches 9% in those younger than 65 years and up to 14% in patients under 45 years of age.⁸

Few studies have assessed the prevalence of FH in Latin America.⁹,¹⁰,¹¹ Using the Dutch Lipid Clinic Network (DLCN) criteria, the prevalence in Brazil has been estimated at 1 in 263 individuals, with some variability attributed to the country’s multiethnic population, while in Argentina the estimated prevalence is 1 in 291.⁹,¹⁰ In Chile, data from the 2010 National Health Survey suggested a prevalence of 1 in 243 individuals; however, this estimate relied solely on very high LDL-C levels (>230 mg/dL) as a proxy for FH and lacked formal clinical or genetic confirmation.¹¹,¹²

Despite the fact that FH is not a rare disorder, most affected individuals remain undiagnosed and, consequently, untreated or inadequately treated.¹ Over the past 3 decades, however, the prognosis of FH has improved substantially owing to increased awareness and knowledge, broader adoption of genetic testing, development and implementation of cascade screening (CS) programs, and the availability of potent lipid-lowering agents beyond statins and ezetimibe, including PCSK9 inhibitors, the small interfering RNA (siRNA) therapy inclisiran, and bempedoic acid.¹,¹³,¹⁴,¹⁵,¹⁶,¹⁷,¹⁸,¹⁹,²⁰ In parallel, national and international clinical practice guidelines and consensus statements have consolidated evidence from genetic studies, therapeutic innovations, clinical trials, and real-world registry data, thereby improving awareness and promoting earlier detection and more intensive management.¹,¹⁵,¹⁶,²¹,²²,²³,²⁴,²⁵

Despite these global advances, their translation into routine clinical practice across Latin America has been limited and uneven. Unequal access to healthcare systems, insufficient knowledge and awareness among healthcare professionals and policymakers, and the limited availability of genetic testing and advanced lipid-lowering therapies continue to hinder early diagnosis and appropriate treatment. In addition, the absence of coordinated screening initiatives and national FH registries in most countries further contributes to the persistent gap between evidence-based recommendations and real-world practice throughout the region.

The objective of this review is to provide a comprehensive and up-to-date overview of the status of FH in Latin America. We summarize prevalence data, screening strategies, diagnostic approaches, genetic findings, and access to therapies across the region, and we highlight the major barriers that continue to limit optimal care. Furthermore, we outline the role of national scientific societies, other professional institutions, and organizations in the development of clinical guidelines, as well as the role of registries and regional collaborative networks. Together, these mechanisms represent essential tools to improve awareness, promote early detection, and support the implementation of evidence-based FH management across Latin America.

BARRIERS AND CHALLENGES IN LATIN AMERICA

The diagnosis and management of FH in Latin America are hindered by a series of structural, economic, and educational barriers that directly affect patient outcomes. Collectively, these challenges contribute to the extremely low detection rates observed across most countries in the region.¹

A major barrier is the marked heterogeneity of healthcare systems across Latin America. Fragmented public and private sectors, geographic inequities, and the limited availability of specialized lipid clinics restrict access to appropriate diagnostic tools, advanced lipid-lowering therapies, and sustained long-term follow-up.²⁶ These disparities disproportionately affect populations living outside major urban centers.

Access to genetic testing remains one of the most critical gaps in FH care. Although genetic confirmation improves diagnostic accuracy, facilitates CS, and provides valuable prognostic information,²⁷ genetic testing is often unavailable, unaffordable, or insufficiently reimbursed in most countries. Limited laboratory capacity, administrative barriers, and concerns related to privacy or potential discrimination further restrict its use.

Insufficient awareness among healthcare professionals, as well as among patients and families affected by FH, represents another key barrier. Studies from various regions consistently demonstrate low familiarity with FH diagnostic criteria, prevalence, and associated ASCVD risk, particularly among primary care physicians, who play a pivotal role in recognizing severe hypercholesterolemia.²⁸,²⁹ From the patient perspective, substantial knowledge gaps are also evident. Individuals with severe hypercholesterolemia often underestimate their cardiovascular risk, and most remain unaware of the hereditary nature of the condition.³⁰ This lack of awareness delays clinical suspicion, may reduce engagement in family-based screening and the initiation of CS, and contributes to lower adherence to long-term treatment.

Therapeutic access across the region is highly variable. Although statins and ezetimibe are widely available, access to more potent agents, such as PCSK9 inhibitors, inclisiran, and bempedoic acid, remains restricted in many countries and is often limited to private healthcare systems (see below). For individuals with homozygous FH (HoFH), access to lomitapide, evinacumab, or LDL apheresis is even more constrained and typically depends on compassionate-use or named-patient programs, thereby creating substantial inequities in care.

Finally, the absence of coordinated national FH programs or population-based registries limits the ability to systematically identify affected individuals, implement CS, and monitor long-term outcomes. These gaps hinder public health planning and slow the development of regional policies aimed at improving FH care.

SCREENING STRATEGIES

Less than 1% of FH cases have been diagnosed in most Latin American countries, with higher detection rates observed primarily in countries that have implemented some form of screening program.¹ Early identification and treatment are fundamental to reducing lifelong exposure to elevated LDL-C levels and preventing premature ASCVD. Three major strategies are globally recognized for FH detection: universal screening (US), opportunistic screening (OS), and CS. Each approach has distinct advantages and limitations, and their feasibility varies substantially across the region.¹,¹⁵,¹⁶,²¹,²²,²³,²⁴,²⁵

US, particularly in childhood, is conceptually attractive because FH is present from birth, and screening at a young age allows early initiation of statin therapy, thereby reducing cumulative LDL-C burden over the life course. Experience with US is largely limited to Slovenia and to regional initiatives in Japan; however, these programs have demonstrated excellent diagnostic yield, feasibility in pediatric settings, and the ability to integrate child–parent screening.³¹,³²,³³,³⁴ Multiple studies worldwide have demonstrated the economic benefits of US when implemented at different ages.³⁵,³⁶ Recently, a probabilistic cost-effectiveness model evaluating pediatric US at age 6 years, corresponding to school entry in Argentina, showed that this strategy could be considered cost-effective.³⁵ This remains the only such study conducted in Latin America. Nevertheless, no country in the region has implemented a formal US program. Barriers include insufficient infrastructure for pediatric screening, limited access to genetic testing, challenges in ensuring follow-up of children and parents, ethical and consent-related considerations, and the overall cost of large-scale screening within resource-constrained healthcare systems.

OS targets individuals with severe hypercholesterolemia, premature ASCVD, or a family history of early cardiovascular events. This strategy is commonly implemented in emergency departments, primary care settings, cardiology units, or through laboratory-based alerts.³⁷,³⁸,³⁹,⁴⁰,⁴¹ OS may be particularly relevant in countries without organized screening programs and can serve as an entry point for developing broader detection strategies, including CS. Several tools have been used globally to enhance OS, such as laboratory alerts for markedly elevated cholesterol levels, interpretative comments on laboratory reports, and electronic case-finding algorithms, some of which have demonstrated cost-effectiveness.⁴² Experience with OS in Latin America remains limited, although initiatives are emerging. In Chile, a pilot study analyzing more than 19,000 unique lipid profiles from a tertiary care center identified nearly 98 suspected FH cases based on LDL-C levels alone.⁴³ In Argentina, the Da Vinci study evaluated a large community-based database of 51,253 adults and found that nearly 4% had total cholesterol levels >300 mg/dL and/or LDL-C ≥190 mg/dL. Among the subgroup that underwent genetic testing (n=69), 33% carried pathogenic variants in the LDLR and APOB genes, while an additional 20% harbored variants in non-traditional genes (ABCG5/8, CYP27A1, LIPA, LIPC, LIPG) or had a high polygenic risk score. These findings highlight a broader genetic heterogeneity than previously recognized in Argentina.¹⁰

CS, which involves testing relatives of an index case using lipid profiles and, when available, genetic testing, is considered the most cost-effective and efficient strategy worldwide for identifying new FH cases.⁴⁴,⁴⁵,⁴⁶ Countries with national CS programs, such as The Netherlands, Norway, Spain, and the United Kingdom, have demonstrated high detection yields and sustained reductions in ASCVD risk.⁴⁷,⁴⁸,⁴⁹,⁵⁰ In the absence of genetic testing, CS can be conducted using country-specific LDL-C thresholds.¹,²¹,⁴⁷ However, reliance solely on lipid levels may fail to identify up to 20% of mutation carriers among relatives, particularly those with LDL-C levels below the 90th percentile.⁵¹

In Latin America, implementation of CS remains limited but is gradually advancing. Since 2010, Brazil has implemented Hipercol Brasil, a genetic CS program in the city of São Paulo, funded by the Brazilian Ministry of Health through the PROADI-SUS initiative.⁵² The program is coordinated by academic centers such as the Heart Institute (InCOR) of the University of São Paulo and collaborates with the public healthcare system by offering free genetic testing for 9 FH-related genes to individuals meeting clinical diagnostic criteria, as well as to their relatives when a pathogenic variant is identified in the proband. The program has demonstrated strong effectiveness, with an average of nearly 2 affected relatives identified per index case during early phases and more than 4 relatives per index case in communities with documented founder effects.⁵²,⁵³

Uruguay is the only country in the region in which FH has been formally incorporated into a national public health program, “GENYCO,” led by the Ministry of Health (https://cardiosalud.org/genetica-cardiovascular/genyco/). This program provides free genetic testing, CS, and guaranteed access to lifelong treatment through both public and private healthcare providers.⁵⁴

Despite these notable successes, most Latin American countries still lack coordinated CS initiatives, representing one of the largest missed opportunities for early FH detection and prevention of premature ASCVD across the region.

CLINICAL DIAGNOSIS AND GENETIC TESTING

Clinical suspicion of FH relies primarily on LDL-C levels, personal and family history of premature ASCVD, and in some cases characteristic physical findings. In children, FH should be suspected when LDL-C is ≥190 mg/dL (4.9 mmol/L) or ≥160 mg/dL (4.1 mmol/L) in the presence of a family history of premature ASCVD or hypercholesterolemia in 1 parent. An LDL-C level ≥135 mg/dL (3.5 mmol/L) in a child with a genetically confirmed affected parent also suggests the diagnosis.⁵⁵ In adults, FH should be suspected in individuals with LDL-C levels ≥190 mg/dL (4.9 mmol/L), in those presenting with ASCVD before age 60 years, or in the presence of physical signs such as tendon xanthomas or premature corneal arcus.¹,²¹,⁴⁷ Several clinical criteria have been developed worldwide for the diagnosis of FH. Among these, the DLCN score is the most widely used. This tool assigns a weighted score based on LDL-C levels, family history of hypercholesterolemia or premature ASCVD, the presence of characteristic clinical signs, and genetic confirmation.⁵⁶ While the DLCN score is applicable only to adults, it requires detailed family information, which is frequently unavailable in many clinical settings across Latin America. Moreover, this score has not been formally validated in the region.

Despite FH being a well-characterized monogenic disorder, access to genetic testing remains limited in most Latin American countries. Testing is frequently unavailable, costly, or not covered by insurance systems. Additional barriers, including limited laboratory capacity and concerns related to privacy, stigmatization, or potential discrimination, further hinder implementation.²⁶,²⁷,⁵⁷

To reduce diagnostic gaps, several collaborative initiatives have emerged across the region. The Ibero-American FH Network, comprising centers in Argentina, Brazil, Chile, Colombia, Mexico, Uruguay, Spain, and Portugal, was established in 2013. This collaboration has facilitated access to molecular testing and generated important genetic data for the region, complementing independent national research efforts.⁵⁸,⁵⁹,⁶⁰,⁶¹,⁶²,⁶³,⁶⁴ Based on published studies and collaborative network data, the most frequent pathogenic variants causing FH in the region are summarized in Fig. 1.⁵⁸,⁵⁹,⁶⁰,⁶¹,⁶²,⁶³,⁶⁴ These findings highlight the presence of shared pathogenic variants in the APOB and LDLR genes across multiple countries, as well as unique, country-specific variants.

Fig. 1. Pathogenic variants in LDLR, APOB, and PCSK9 genes described in selected Latin American countries.⁵⁸,⁵⁹,⁶⁰,⁶¹,⁶²,⁶³,⁶⁴ .

LDLR, low-density lipoprotein receptor gene; APOB, apolipoprotein B-100; PCSK9, proprotein convertase subtilisin/kexin type 9.

To date, only 2 countries in Latin America have implemented systematic genetic testing programs integrated into public health strategies: Brazil (Hipercol Brasil) and Uruguay (GENYCO). In the remainder of the region, genetic testing remains largely confined to research settings or specialized centers, such as those in Argentina, Chile, Colombia, and Mexico.

Strengthening molecular diagnostic capacity across Latin America will be essential to expanding CS, improving early detection, and reducing the clinical impact of undiagnosed FH throughout the region.

LDL-C GOAL ATTAINMENT IN LATIN AMERICA

The primary treatment objectives in FH are to reduce LDL-C levels and to lower the risk of ASCVD. The 2019 European guidelines and the recent 2025 focused update recommend at least a 50% reduction in LDL-C levels, with specific LDL-C targets based on cardiovascular risk.¹⁴ In very high-risk adults (FH with ASCVD or with at least 1 major cardiovascular risk factor, such as diabetes mellitus, hypertension, smoking, or elevated lipoprotein(a)), the recommended target is <55 mg/dL. In high-risk adults (FH without major cardiovascular risk factors), the target is <70 mg/dL. Achieving these targets is particularly challenging in Latin America, as most patients do not attain adequate LDL-C reduction with statin monotherapy and therefore require high-intensity statins in combination with ezetimibe and, in many cases, PCSK9 inhibitors. Although these therapies have demonstrated substantial improvements in LDL-C control, their availability in the region is limited and they are not consistently covered by social security systems or insurance providers. The Familial Hypercholesterolemia Studies Collaboration (FHSC) registry reported that although more than 70% of individuals from the Americas were receiving lipid-lowering therapy, median LDL-C levels remained around 5.8 mmol/L (225 mg/dL), well above recommended targets.⁶⁵ This finding is partly attributable to the predominant use of statins as monotherapy. Recent data from Mexico and Brazil corroborate these observations. In Mexico, statin use is very high (88%); however, only half of patients receive high-intensity statins, 35% receive ezetimibe, and 7.5% are treated with PCSK9 inhibitors. LDL-C goal attainment is consequently very low, with 6% of patients achieving LDL-C <70 mg/dL and only 4% achieving <55 mg/dL.⁶⁶ In Brazil, nearly 90% of individuals with FH receive high-intensity lipid-lowering therapy; however, PCSK9 inhibitor use remains extremely low (2%), and only 3% of patients achieve LDL-C <70 mg/dL.⁶⁷ Recent real-world evidence from Argentina further illustrates the magnitude of the treatment gap in severe hypercholesterolemia across the region. After 5 years of follow-up, only one-third of patients remained on statin therapy, none achieved LDL-C targets, and multiple barriers related to follow-up, access, and physician oversight were reported.⁶⁸

LIPID-LOWERING TREATMENTS IN LATIN AMERICA

While timely identification and intensive lipid-lowering therapy substantially reduce premature cardiovascular events and improve long-term outcomes, major disparities persist across countries with respect to therapy availability, reimbursement systems, and physician awareness. These differences ultimately result in suboptimal care and the undertreatment of affected individuals. Several countries in Latin America have published national or society-endorsed recommendations for FH in recent years (Table 1); however, implementation remains challenging, particularly with regard to diagnosis, screening strategies, and access to lipid-lowering therapies.²³,²⁴,⁶⁹ To date, no country in the region has established a nationwide ministerial FH program. Statins and ezetimibe are widely available and are generally included within both public and private formularies across most Latin American countries. Both remain the cornerstone of FH management. In contrast, access to newer and highly potent lipid-lowering agents remains restricted. Monoclonal antibodies against PCSK9 (alirocumab and evolocumab), the siRNA inclisiran, and bempedoic acid are not universally available and are largely confined to tertiary reference centers or private healthcare systems in some countries. Their inclusion in national reimbursement lists is limited, and prescription frequently depends on special authorization mechanisms, including judicial processes (“amparos”). For patients with HoFH, access to highly specialized therapies such as lomitapide and evinacumab is even more limited. These treatments are usually available only through named-patient programs, importation pathways, or industry-supported compassionate-use initiatives. LDL apheresis remains an alternative in a very small number of selected centers in Brazil and Argentina; however, it is not available or reimbursed at a national level through public insurance systems.

Table 1. Availability of national clinical guidelines published within the last 5 years for the diagnosis and management of FH.

Country	National FH guideline	Year	Institution	Reference
Argentina*		2024	Argentine Lipid Society	23
Brazil		2021	Brazilian Society of Cardiology	24
Chile†
Colombia		2024	Colombian Society of Cardiology	69
Ecuador
Mexico
Perú
Dominican Republic
Uruguay‡		2024	National Ministry of Health	-
Venezuela

FH, familial hypercholesterolemia.

^*Argentina, guideline available specifically for the homozygous form (homozygous FH).

^†Chile, technical guidelines for dyslipidemia are from 2018 (no update available).

^‡Uruguay, obtained from https://www.gub.uy/ministerio-salud-publica/.

The availability and coverage of key lipid-lowering therapies, including those indicated for HoFH and LDL apheresis, are summarized in Table 2.

Table 2. Availability of non-statin lipid-lowering therapies in selected Latin American countries for the management of familial hypercholesterolemia.

Variables	Argentina	Brazil	Chile	Colombia	Dominican Republic	Ecuador	Mexico	Perú	Uruguay	Venezuela
Ezetimibe
PCSK9i
Bempedoic acid
Inclisiran
Evinacumab
Lomitapide
Low-density lipoprotein apheresis	*	*

PCSK9i, proprotein convertase subtilisin/kexin type inhibitor.

^*Low-density lipoprotein apheresis is available in few selected centers in Argentina and Brazil; however, it is not routinely available and reimbursed at the national level.

ROLE OF CLINICAL REGISTRIES IN FH

Over the past decade, the development of clinical registries has substantially improved our understanding of FH. Real-world data collected from routine clinical practice across diverse settings have provided insights into the molecular basis of the disorder, the heterogeneity of its clinical expression, and the contribution of additional cardiovascular risk factors, such as lipoprotein(a). Registries have also highlighted gaps in lipid-lowering treatment, the degree of implementation of clinical guidelines, and the extent of LDL-C goal attainment.⁷⁰ One example of a registry with a demonstrable positive impact on FH care is SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Follow-up Study). Established in 2004, it has prospectively followed more than 5,000 individuals, including genetically confirmed FH patients and their unaffected relatives. Analyses derived from this registry have generated robust evidence that contributed to the development of cascade genetic screening in several regions of Spain and facilitated reimbursement for all available lipid-lowering therapies.¹⁸,⁷¹,⁷² At a global level, the FHSC has established a standardized and harmonized registry including more than 42,000 adults from 56 countries, of whom approximately 3,200 are from the Americas. The first cross-sectional analysis demonstrated that FH is diagnosed late in the Americas, at a mean age of approximately 46 years, and that LDL-C control remains far from guideline-recommended targets. This gap is partly attributable to reliance on statin monotherapy and the limited use of combination lipid-lowering therapy.⁶⁵ In Latin America, national registries have been initiated in Mexico, Colombia, and Brazil, as well as smaller, more localized registries in countries such as Argentina and Chile.¹⁰,⁵³,⁶⁶,⁷³ These initiatives will support research, improve understanding of the regional realities of FH, identify specific care needs, and ultimately contribute to the development of more effective care models and better-informed policy decisions.

CONCLUSIONS

With more than 2 million people living with FH in Latin America, the region continues to face significant challenges that hinder optimal detection, diagnosis, and long-term care. Despite the high prevalence of FH and its severe cardiovascular consequences, interconnected structural, educational, and systemic barriers perpetuate the underdiagnosis and undertreatment of the condition. Recognizing and addressing these barriers at both national and regional levels is essential to reducing the burden of FH across Latin America. This underscores the urgent need for implementation of clinical practice guidelines that include systematic identification, structured CS, and equitable access to effective lipid-lowering therapies.

1. Highlights

• • Insufficient awareness and knowledge among healthcare providers: Low familiarity with FH, particularly among general practitioners, regarding diagnostic criteria, screening strategies, and the magnitude of cardiovascular risk delays diagnosis and CS. Less than 50% of general practitioners are familiar with the disorder, and the majority underestimate the associated cardiovascular risk.

• • Lack of coordinated national programs and screening approaches: With the exception of Uruguay’s GENYCO initiative and Brazil’s Hipercol Brasil program, most countries lack national, coordinated FH detection and CS strategies.

• • Scarcity of genetic testing: Although genetic testing provides definitive diagnostic confirmation, supports risk stratification, and enables effective CS, its availability remains limited in many Latin American countries. Genetic confirmation is typically restricted to academic or research laboratories and is rarely reimbursed by health insurers.

• • Fragmented healthcare systems and socioeconomic disparities: Poor integration between public and private healthcare sectors leads to unequal access and inadequate referral pathways for specialized care. Geographic barriers and socioeconomic inequalities further restrict access to specialists, laboratory resources, and long-term follow-up.

• • Limited access to new medications and reimbursement: The high cost and restricted coverage of newer agents, including PCSK9 inhibitors, siRNA-based therapies, bempedoic acid, lomitapide, and evinacumab (the latter 2 for HoFH), prevent their widespread clinical use.

• • Patient awareness: Substantial gaps in patients’ understanding of their cardiovascular risk and the implications of FH contribute to suboptimal adherence, inadequate disease management, and delayed or reduced long-term engagement with healthcare services.