Familial hypercholesterolemia (FH) remains underdiagnosed despite widespread cholesterol screening. Exome sequencing and electronic health record (EHR) data of 50,726 individuals were used to assess the prevalence and clinical impact of FH-associated genomic variants in the Geisinger Health System. The estimated FH prevalence was 1:256 in unselected participants and 1:118 in participants ascertained via the cardiac catheterization laboratory. FH variant carriers had significantly increased risk of coronary artery disease. Only 24% of carriers met EHR-based presequencing criteria for probable or definite FH diagnosis. Active statin use was identified in 58% of carriers; 46% of statin-treated carriers had a low-density lipoprotein cholesterol level below 100 mg/dl. Thus, we find that genomic screening can prompt the diagnosis of FH patients, most of whom are receiving inadequate lipid-lowering therapy.

Purpose Three genetic conditions—hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia—have tier 1 evidence for interventions that reduce morbidity and mortality, prompting proposals to screen unselected populations for these conditions. We examined the impact of genomic screening on risk management and early detection in an unselected population. Methods Observational study of electronic health records (EHR) among individuals in whom a pathogenic/likely pathogenic variant in a tier 1 gene was discovered through Geisinger’s MyCode project. EHR of all eligible participants was evaluated for a prior genetic diagnosis and, among participants without such a diagnosis, relevant personal/family history, postdisclosure clinical diagnoses, and postdisclosure risk management. Results Eighty-seven percent of participants (305/351) did not have a prior genetic diagnosis of their tier 1 result. Of these, 65% had EHR evidence of relevant personal and/or family history of disease. Of 255 individuals eligible to have risk management, 70% ( n = 179) had a recommended risk management procedure after results disclosure. Thirteen percent of participants (41/305) received a relevant clinical diagnosis after results disclosure. Conclusion Genomic screening programs can identify previously unrecognized individuals at increased risk of cancer and heart disease and facilitate risk management and early cancer detection.

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Background Numerous implementation strategies to improve utilization of statins in patients with hypercholesterolemia have been utilized, with varying degrees of success. The aim of this systematic review is to determine the state of evidence of implementation strategies on the uptake of statins. Methods and results This systematic review identified and categorized implementation strategies, according to the Expert Recommendations for Implementing Change (ERIC) compilation, used in studies to improve statin use. We searched Ovid MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov from inception to October 2018. All included studies were reported in English and had at least one strategy to promote statin uptake that could be categorized using the ERIC compilation. Data extraction was completed independently, in duplicate, and disagreements were resolved by consensus. We extracted LDL-C (concentration and target achievement), statin prescribing, and statin adherence (percentage and target achievement). A total of 258 strategies were used across 86 trials. The median number of strategies used was 3 (SD 2.2, range 1–13). Implementation strategy descriptions often did not include key defining characteristics: temporality was reported in 59%, dose in 52%, affected outcome in 9%, and justification in 6%. Thirty-one trials reported at least 1 of the 3 outcomes of interest: significantly reduced LDL-C (standardized mean difference [SMD] − 0.17, 95% CI − 0.27 to − 0.07, p = 0.0006; odds ratio [OR] 1.33, 95% CI 1.13 to 1.58, p = 0.0008), increased rates of statin prescribing (OR 2.21, 95% CI 1.60 to 3.06, p < 0.0001), and improved statin adherence (SMD 0.13, 95% CI 0.06 to 0.19; p = 0.0002; OR 1.30, 95% CI 1.04 to 1.63, p = 0.023). The number of implementation strategies used per study positively influenced the efficacy outcomes. Conclusion Although studies demonstrated improved statin prescribing, statin adherence, and reduced LDL-C, no single strategy or group of strategies consistently improved outcomes. Trial registration PROSPERO CRD42018114952.

Background Familial hypercholesterolemia (FH) is an inherited lipid disorder that confers high risk for premature cardiovascular disease but remains undertreated. Causes are multifactorial and multilevel, ranging from underprescribing (at the clinician-level) to medication nonadherence (at the patient-level). We evaluated patient and clinician stakeholder barriers and facilitators for treatment of FH to explore possible solutions to the problem. Methods and results Semi-structured interviews and focus groups guided by the Practical, Robust, Implementation and Sustainability Model (PRISM), were conducted with 33 patients and 17 clinician stakeholders across three healthcare systems. A total of14 patients and 9 clinician stakeholders participated in on-site focus groups and the remainder were individual interviews. Transcripts were coded using an iterative process to create a static codebook. We characterized patient and clinician stakeholder barriers into three categories: medical care-, medication-, and life-related. Feasibility of brainstormed solutions varied and was not always representative of the needs of all stakeholders. Patients suggested a need for childhood screening for FH and doctors being persistent about the importance of treating FH, creation of a patient peer group, data transparency, advocacy, and policy changes that would enable patients to receive better treatment. Clinician stakeholders suggested the need for clinical champions. Both groups of stakeholders discussed the need for education about FH. Conclusions Proposed solutions to improve treatment of FH proffered by participants in this study included resources for both patients and clinician stakeholders that clarify cardiovascular disease risks from FH, develop programs to screen for and identify FH at younger ages, and foster open conversations between patients and clinicians about treatment.

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Background Familial hypercholesterolemia ( FH ), is a historically underdiagnosed, undertreated, high‐risk condition that is associated with a high burden of cardiovascular morbidity and mortality. In this study, we use a population‐based approach using electronic health record ( EHR )‐based algorithms to identify FH . We report the major adverse cardiovascular events, mortality, and cost of medical care associated with this diagnosis. Methods and Results In our 1.18 million EHR‐ eligible cohort, International Classification of Diseases, Ninth Revision ( ICD ‐9 ) code‐defined hyperlipidemia was categorized into FH and non‐ FH groups using an EHR algorithm designed using the modified Dutch Lipid Clinic Network criteria. Major adverse cardiovascular events, mortality, and cost of medical care were analyzed. A priori associated variables/confounders were used for multivariate analyses using binary logistic regression and linear regression with propensity score–based weighted methods as appropriate. EHR FH was identified in 32 613 individuals, which was 2.7% of the 1.18 million EHR cohort and 13.7% of 237 903 patients with hyperlipidemia. FH had higher rates of myocardial infarction (14.77% versus 8.33%; P <0.0001), heart failure (11.82% versus 10.50%; P <0.0001), and, after adjusting for traditional risk factors, significantly correlated to a composite major adverse cardiovascular events variable (odds ratio, 4.02; 95% CI, 3.88–4.16; P <0.0001), mortality (odds ratio, 1.20; CI, 1.15–1.26; P <0.0001), and higher total revenue per‐year (incidence rate ratio, 1.30; 95% CI, 1.28–1.33; P <0.0001). Conclusions EHR ‐based algorithms discovered a disproportionately high prevalence of FH in our medical cohort, which was associated with worse outcomes and higher costs of medical care. This data‐driven approach allows for a more precise method to identify traditionally high‐risk groups within large populations allowing for targeted prevention and therapeutic strategies.

The Geisinger MTDM program has evolved over 20 years from a single pharmacist-run anticoagulation clinic into a large program focused on managing the health of an ever-growing population. Initial challenges in integrating pharmacists into the Geisinger patient care framework as clinical experts were overcome by demonstrating the MTDM program's positive impact on patient outcomes.