Abstract

Background

Familial hypercholesterolaemia is a common inherited condition that is associated with premature cardiovascular disease. The increased cardiovascular morbidity and mortality, resulting from high levels of cholesterol since birth, can be prevented by starting lipid‐lowering therapy. However, the majority of patients in the UK and worldwide remain undiagnosed. Established diagnostic criteria in current clinical practice are the Simon‐Broome and Dutch Lipid Clinical network criteria and patients are classified as having probable, possible or definite familial hypercholesterolaemia.

Objectives

To assess the effectiveness of healthcare interventions strategies to systematically improve identification of familial hypercholesterolaemia in primary care and other community settings compared to usual care (incidental approaches to identify familial hypercholesterolaemia in primary care and other community settings).

Search methods

We searched the Cochrane Inborn Errors of Metabolism Trials Register. Date of last search: 13 September 2021.

We also searched databases (Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, PubMed, Embase, CINAHL, Web of Science, and SCOPUS) as well as handsearching relevant conference proceedings, reference lists of included articles, and the grey literature. Date of last searches: 05 March 2020. 

Selection criteria

As per the Effective Practice and Organisation of Care (EPOC) Group guidelines, we planned to include randomised controlled trials (RCTs), cluster‐RCTs and non‐randomised studies of interventions (NRSI). Eligible NRSI were non‐randomised controlled trials, prospective cohort studies, controlled before‐and‐after studies, and interrupted‐time‐series studies.

We planned to selected studies with healthcare interventions strategies that aimed to systematically identify people with possible or definite clinical familial hypercholesterolaemia, in primary care and other community settings. These strategies would be compared with usual care or no intervention.

We considered participants of any age from the general population who access primary care and other community settings.

Data collection and analysis

Two authors planned to independently select studies according to the inclusion criteria, to extract data and assess for risk of bias and the certainty of the evidence (according to the GRADE criteria). We contacted corresponding study authors in order to obtain further information for all the studies considered in the review.

Main results

No eligible RCTs or NRSIs were identified for inclusion, however, we excluded 28 studies.

Authors' conclusions

Currently, there are no RCTs or controlled NRSI evidence to determine the most appropriate healthcare strategy to systematically identify possible or definite clinical familial hypercholesterolaemia in primary care or other community settings. Uncontrolled before‐and‐after studies were identified, but were not eligible for inclusion. Further studies assessing healthcare strategies of systematic identification of familial hypercholesterolaemia need to be conducted with diagnosis confirmed by genetic testing or validated through clinical phenotype (or both).

Author(s)

Nadeem Qureshi, Maria Luisa R Da Silva, Hasidah Abdul-Hamid, Stephen F Weng, Joe Kai, Jo Leonardi-Bee

Abstract

Plain language summary

Healthcare strategies for identifying possible or definite clinical familial hypercholesterolaemia in primary care and other community settings

Background

One of the most common inherited conditions is familial hypercholesterolaemia, people with this condition have raised cholesterol from birth. This condition can result in the arteries being narrowed by excess cholesterol sticking to their walls and can lead to heart disease at an early age. However, treatment with cholesterol‐lowering tablets markedly reduces this risk.

As well as raised cholesterol in the blood, family history of heart disease and the presence of fatty lumps under the skin could indicate familial hypercholesterolaemia.

It is important that community‐based health professionals, such as general practitioners and community pharmacists, can identify those at risk of possible or probable familial hypercholesterolaemia and refer them to a specialist. Specialists can confirm a diagnosis of familial hypercholesterolaemia through examination and a genetic test.

This review explores the impact of these healthcare strategies in primary care and other community settings to systematically identify people with possible and definite clinical familial hypercholesterolaemia.

Search date

13 September 2021.

Study characteristics

We did not find any studies that we could include in this review.

Key results

There were no studies eligible for inclusion in the review.

Quality of evidence

There were no studies included in the review.

Conclusions

Currently, there is a lack of evidence regarding the most appropriate healthcare strategy to identify possible or definite clinical familial hypercholesterolaemia in primary care and other community settings. Better‐designed studies, with diagnosis of definite familial hypercholesterolaemia confirmed by genetic tests, are needed to clearly answer this question.

Author(s)

Nadeem Qureshi, Maria Luisa R Da Silva, Hasidah Abdul-Hamid, Stephen F Weng, Joe Kai, Jo Leonardi-Bee

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

The review provided no evidence from randomised controlled trials or controlled non‐randomised studies to inform the most effective healthcare strategy for identifying familial hypercholesterolaemia (FH) in primary care and other community settings. However, there is a potential role for searching primary care electronic health records.

Implications for research 

A pragmatic trial design should be adopted to answer this research question using different diagnostic assessment criteria in primary care electronic health records. Genetic confirmation of FH should be included, as well as a detailed description of processes and outcome measures, particularly referral to specialists and both surrogate and disease outcome measures of cardiovascular disease. To identify later results for clinical outcome measures, at least one year study follow‐up would be required. Considering the current evidence of the benefits of identifying FH, a study design using a true control group with no active identification maybe ethically unacceptable.

Internationally, considering the primary outcome measure proposed in this systematic review, the most commonly used diagnostic assessment criteria for FH is the Dutch Lipid Clinic Network (DLCN) (Defesche 2004; Reiner 2011; Watts 2011). In the UK, Simon‐Broome criteria is the most frequently used, as recommended by the original 2008 NICE guidelines on FH and the updated version in 2017 (NICE 2008; NICE 2017). Other assessment criteria have also been used worldwide, such as MedPed (Williams 1993), the Japanese criteria (Harada‐Shiba 2012) and the Canadian criteria (Ruel 2018). It would be challenging to combine studies using different diagnostic assessment criteria. Although several of the criteria include genetic testing, such as DLCN and Simon‐Broome criteria, currently genetic testing is not routinely performed in primary care (Green 2016; Qureshi 2016). Hence the primary outcome measure directly collated from primary care will be based on clinical phenotype. When genetically‐confirmed FH is collated, this is currently based on the diagnosis of those people referred from primary to specialist care.

Get full text at The Cochrane Library