Knowing the Prevalence of Familial Hypercholesterolemia Matters

Goldberg, Anne C.; Gidding, Samuel S.

doi:10.1161/circulationaha.116.021673

Cited by 32 publications

(11 citation statements)

References 20 publications

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“…Cholesterol homeostasis is vital for sustaining life since it is one of the pivotal constituents of cellular membrane and myelin sheath of neurons 47 . However, altered cholesterol homeostasis mostly due to its elevated levels in blood (hypercholesterolemia) has become a global health concern as it not only associated with cardiovascular diseases but also a prognostic risk factor for neurodegenerative disorders, particularly AD 30 , 46 – 49 . Recently, we have demonstrated that hypercholesterolemia in mice can cause Parkinson’s disease (PD)-like pathology and exaggerates the parkinsonian symptoms as well as pathologies in animal model of PD 30 , 31 , 34 .…”

Section: Discussionmentioning

confidence: 99%

Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice

Paul

Borah

2017

Sci Rep

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There exists an intricate relationship between hypercholesterolemia (elevated plasma cholesterol) and brain functions. The present study aims to understand the impact of hypercholesterolemia on pathological consequences in mouse brain. A chronic mouse model of hypercholesterolemia was induced by giving high-cholesterol diet for 12 weeks. The hypercholesterolemic mice developed cognitive impairment as evident from object recognition memory test. Cholesterol accumulation was observed in four discrete brain regions, such as cortex, striatum, hippocampus and substantia nigra along with significantly damaged blood-brain barrier by hypercholesterolemia. The crucial finding is the loss of acetylcholinesterase activity with mitochondrial dysfunction globally in the brain of hypercholesterolemic mice, which is related to the levels of cholesterol. Moreover, the levels of hydroxyl radical were elevated in the regions of brain where the activity of mitochondrial complexes was found to be reduced. Intriguingly, elevations of inflammatory stress markers in the cholesterol-rich brain regions were observed. As cognitive impairment, diminished brain acetylcholinesterase activity, mitochondrial dysfunctions, and inflammation are the prima facie pathologies of neurodegenerative diseases, the findings impose hypercholesterolemia as potential risk factor towards brain dysfunction.

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Section: Discussionmentioning

confidence: 99%

Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice

Paul

Borah

2017

Sci Rep

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“…1 , 2 FDA-labeled disease indications for PCSK-9 inhibitors include clinical atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia (FH), a genetic metabolic disorder affecting about 0.4% of adults. 3 , 4 In Europe, the medications are approved for a somewhat broader list of diagnoses, including FH, non-FH, and mixed dyslipidemia. 5 …”

Section: Introductionmentioning

confidence: 99%

Real-world use of PCSK-9 inhibitors by early adopters: cardiovascular risk factors, statin co-treatment, and short-term adherence in routine clinical practice

Fairman¹,

Davis²,

Sclar³

2017

TCRM

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BackgroundInconsistency of real-world medication use with labeled indications may affect cost and clinical value of pharmacotherapy. PCSK-9 inhibitors are labeled in the US for use with statins to reduce low-density lipoprotein cholesterol in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH).ObjectiveTo assess consistency with labeled indications and treatment persistency for early (first 5 post-launch months) adopters of PCSK-9 inhibitor pharmacotherapy.MethodsRetrospective analysis of commercially insured cohorts derived from the Truven Health MarketScan® database was performed. Subjects were aged 18–64 years, initiated PCSK-9 inhibitor or highest-intensity statin (rosuvastatin 40 mg/day or atorvastatin 80 mg/day) pharmacotherapy from August to December 2015, and were enrolled throughout 2015 and during separate baseline (pre-treatment) periods of 6 and 18 months. Baseline ASCVD, FH, and ASCVD events (myocardial infarction, transient ischemic attack, and cerebrovascular occlusion) were measured. Persistency was measured through December 2015 for subcohorts of patients initiating treatment from August to September 2015.ResultsBaseline disease rates were higher for patients treated with PCSK-9 inhibitors (n=390) compared with highest-intensity statins (n=26,306): ASCVD (68.5% vs 33.4%, respectively); FH (39.7% vs 15.5%); both P<0.001. In 18 months pre-treatment, 35.6% of PCSK-9 inhibitor-treated patients had ≥1 ASCVD event, and 87.9% had a labeled indication. Rates of 60-day nonpersistency for PCSK-9 inhibitors and highest-intensity statins were 33.3% and 39.8%, respectively (P=0.207). During PCSK-9 inhibitor pharmacotherapy, 33.8% of patients had evidence of statin supply and, of those initiating treatment from August to September, 40.9% filled ≥1 statin prescription. Of those with sustained pre-treatment statin use, 34.8% had no statin supply during PCSK-9 inhibitor pharmacotherapy.ConclusionAmong early-adopting PCSK-9 inhibitor-treated patients, the off-label diagnosis rate was 12%; a majority lacked statin co-treatment; and one third filled prescriptions for ≤60 days. Inconsistency with labeled uses may reflect prescriber/patient decisions, health-insurance coverage determinations, or statin intolerance not reported on claims.

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“…Prevalence data enable the design of screening programs for FH in the community 31) . We have completed studies in China and Australia, where the prevalence of heterozygous FH was found to be 1:211 -359 32) and 1:229 -353 33) , respectively, consistent with recent findings from the US 34) and Europe 35,36) .…”

Section: (2) Epidemiology: Prevalence Of Fh In Community and High-rismentioning

confidence: 99%

Translational Research for Improving the Care of Familial Hypercholesterolemia: The “Ten Countries Study” and Beyond

Watts

Ding²,

George

et al. 2016

J Atheroscler Thromb

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Familial hypercholesterolemia (FH) is the most common and serious form of inherited hyperlipidaemia. Dominantly inherited with high penetrance, untreated FH leads to premature death from coronary artery disease due to accelerated atherosclerosis from birth. Despite its importance, there is still a major shortfall in awareness, detection and treatment of FH worldwide. International models of care for FH have recently been published, but their effective implementation requires the garnering of more knowledge about the condition. The "Ten Countries Study" aims to investigate diagnostic, epidemiological and service aspects, as well as physician practices and patient experiences of FH in several countries in the Asia-Pacific Region and the Southern Hemisphere. Five observational studies are being undertaken that will systematically investigate the following aspects of FH: the phenotypic predictors of low-density lipoprotein receptor mutations, the point prevalence in available community populations, current knowledge and clinical practices among primary care physicians, availability and utilisation of services and facilities, and patient perceptions and personal experiences of the condition. The information gathered will inform better clinical practice and will enable the development of country-specific models of care for FH.

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Knowing the Prevalence of Familial Hypercholesterolemia Matters

Cited by 32 publications

References 20 publications

Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice

Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice

Real-world use of PCSK-9 inhibitors by early adopters: cardiovascular risk factors, statin co-treatment, and short-term adherence in routine clinical practice

Translational Research for Improving the Care of Familial Hypercholesterolemia: The “Ten Countries Study” and Beyond

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