Statins for children with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review. OBJECTIVES: To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia. SEARCH METHODS: Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline. Date of most recent search: 04 November 2019. SELECTION CRITERIA: Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion and extracted data. MAIN RESULTS: We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (high-quality evidence). There may be little or no difference in liver function (serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations) between treated and placebo groups at any time point (low-quality evidence). There may be little or no difference in myopathy (as measured in change in creatinine levels) (low-quality evidence) or clinical adverse events (moderate-quality evidence) with statins compared to placebo. One study on simvastatin showed that this may slightly improve flow-mediated dilatation of the brachial artery (low-quality evidence), and on pravastatin for two years may have induced a regression in carotid intima media thickness (low-quality evidence). No studies reported rhabdomyolysis (degeneration of skeletal muscle tissue) or death due to rhabdomyolysis, quality of life or compliance to study medication. AUTHORS' CONCLUSIONS: Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. Few or no safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.

Statins for children with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review. OBJECTIVES: To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia. SEARCH METHODS: Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of most recent search: 20 February 2017. SELECTION CRITERIA: Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion and extracted data. MAIN RESULTS: We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (moderate quality evidence). Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point (low quality evidence). The risks of myopathy (low quality evidence) and clinical adverse events (moderate quality evidence) were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery (low quality evidence), and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness (low quality evidence). AUTHORS' CONCLUSIONS: Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.

General Aviation Pilots Over 70 Years Old.

BACKGROUND: Currently it is not unusual for general aviation pilots in the United States to continue to fly beyond the age of 70, even into their 80s and 90s. Pilots have regular examinations according to protocols which do not specify special or additional requirements for pilots over 70 yr of age. Additionally, the third class medical reforms passed by the U.S. Senate on 15 July 2016 could potentially result in even less stringent medical certification requirements for general aviation pilots. METHODS: Accident rates, medical parameters, autopsy findings, and toxicological findings from the U.S. National Transportation Safety Board (NTSB) general aviation (GA) accident database were analyzed to assess potential risk factors with accident outcomes. RESULTS: During 2003-2012, there were 114 (113 men, 1 woman) general aviation fatal accidents involving pilots ages 70 to 92 yr. A combination of 3 or more drugs were found in 13 (13%) of deceased pilots. The most frequent drugs were first generation antihistamines and antidepressants represented the next highest proportion of possible performance-affecting medications. CONCLUSION: This study indicates that there are critical medical factors that may contribute to fatal accidents among elderly pilots. Polypharmacy use should be taken into consideration, especially during periodic health examinations and fatal aviation investigations involving elderly pilots.Vuorio A, Asmayawati S, Budowle B, Griffiths R, Strandberg T, Kuoppala J, Sajantila A. General aviation pilots over 70 years old. Aerosp Med Hum Perform. 2017; 88(2):142-145.

Statins for children with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia is one of the most common inherited metabolic diseases; the average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500. Diagnosis of familial hypercholesterolemia in children is based on highly elevated low-density lipoprotein (LDL) cholesterol level or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong hypolipidemic measures, started in childhood, are needed to reduce the risk of cardiovascular disease. In children with familial hypercholesterolemia, diet is as yet the cornerstone of treatment. Anion exchange resins, such as cholestyramine and colestipol, have also been found to be effective, but are poorly tolerated. Since the 1990s statin studies have been carried out among children with familial hypercholesterolemia (aged 7 to 17 years). Statins greatly reduced their serum LDL cholesterol levels. Even though statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. OBJECTIVES: To assess the effectiveness and safety of statins in children with familial hypercholesterolemia. SEARCH METHODS: Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of most recent search: 14 October 2013. SELECTION CRITERIA: Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion and extracted data. MAIN RESULTS: We found 21 potentially eligible studies, of which we included eight randomized placebo-controlled studies (1074 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean LDL cholesterol concentration at all time points. Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point. The risks of myopathy and clinical adverse events were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery, and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness. AUTHORS' CONCLUSIONS: Statin treatment is an efficient lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety is unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians or physicians into adulthood. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.

The Northern Finland Birth Cohort Eye Study: Design and baseline characteristics.

BACKGROUND: To describe the rationale and design of the Northern Finland Birth Cohort (NFBC) Eye Study. METHODS: The NFBC Eye Study is a randomised prospective cohort study. The original NFBC study population consists of 12058 subjects born in the region of Lapland and the Province of Oulu. A postal questionnaire covering extensively the medical and socioeconomical background was sent to the 10300 subjects of the NFBC alive and residing in Finland. For the NFBC eye study the subjects were randomised to the screening group (50%) and the control group (50%). The screening protocol includes the following tests: automated and manifest refraction, best corrected visual acuity, central corneal thickness, intraocular pressure, Humphrey 24-2 perimetry, stereoscopic optic nerve head (ONH) and retinal nerve fibre layer (RNFL) photography and imaging with Scanning Laser Ophthalmoscopy (HRT), Scanning Laser Polarimetry (GDx) and Optical Coherence Tomography (OCT).Two ophthalmologists evaluate the ONH and RNFL photographs and the visual fields independently. All suspected glaucoma cases are re-evaluated by two independent glaucoma experts. HRT, GDx and OCT findings are assessed separately. In the future, both groups (100%) will be examined. The effectiveness and the cost-effectiveness of glaucoma screening will be calculated. The response rate of the questionnaire was 67% (n = 6855) and 871 randomised subjects had undergone the eye screening protocol by the end of April 2013. DISCUSSION: The trial is designed to address the following questions: what is the best combination of diagnostic tests for detecting glaucoma in an unscreened population, what are the benefits and disadvantages of the screening to the individual and the society and is glaucoma screening both effective and cost-effective. The prevalence, incidence and risk factors of glaucoma and other eye diseases will be evaluated, as well as their impact on quality of life.

Statin treatment of children with familial hypercholesterolemia--trying to balance incomplete evidence of long-term safety and clinical accountability: are we approaching a consensus?

In the heterozygous form of familial hypercholesterolemia (FH), blood concentrations of low-density lipoprotein cholesterol (LDL-C) are elevated two to three times above the normal range since birth, and cause strongly elevated risk of premature coronary artery disease (CAD). There is no evidence that statin therapy is unsafe in FH children, and it has not been associated with clinically significant changes in measures of growth or maturation, liver enzymes, serum creatine kinase, or incidence of myopathy. However, the opinions among clinicians, and between countries, about the age at which statin therapy should be initiated in FH children vary. This review attempts to critically examine the available data, so that clinically the most appropriate age of initiating statin treatment in FH children as a preventive measure for future CAD could be established.

The Pyhäjärvi Cataract Study II. Criteria for cataract surgery.

PURPOSE: It is necessary to develop tools for patient selection to target cataract surgery to patients with the best expected outcomes. We used visual acuity, visual functioning 14 (VF-14) test, the 15-dimension health-related quality-of-life questionnaire (15D) and the New Zealand priority criteria to evaluate the criteria for cataract surgery in a post hoc setting. MATERIAL AND METHODS: Ninety-three consecutive patients living in a defined rural area in Finland had cataract surgery as a part of the Pyhäjärvi Cataract Study in 2003. Success of cataract surgery was defined as improvement of visual acuity by at least 2 lines and/or improvement of visual function measured by questionnaires. RESULTS: The patients with a visual acuity of 0.30 logMAR (0.5 Snellen decimal) or worse in the better eye and/or 0.52 logMAR (0.3 Snellen decimal) in the worse eye had successful surgery in 59-83% of cases depending on the definition of success. When subjective judgement was added, the success rates varied between 63% and 91%. CONCLUSION: Setting indication criteria, it seems sufficient to use two global questions in addition to visual acuity: one on the subjective view on disability, and one on a more neutral view on visual function, such as the 15D item on vision. The VF-14 did not perform any better than the single item counterparts.

Statins for children with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia is one of the most common inherited metabolic diseases; the average worldwide prevalence of heterozygous familial hypercholesterolemia is about 1 in 500. Diagnosis of familial hypercholesterolemia in children is based on two measurements of low-density lipoprotein cholesterol level above 4.0 mmol/L or a DNA-based analysis. Coronary stenosis has been detected in men with familial hypercholesterolemia as young as 17 years old and in women with familial hypercholesterolemia at 25 years old. Atherosclerosis and its clinical complications occur prematurely, especially in men, thus lifelong hypolipidemic measures, started in childhood, are needed to reduce the risk of cardiovascular diseases. In children with familial hypercholesterolemia children, so far diet has been the main mode of treatment. Anion exchange resins, such as cholestyramine and colestipol, have also been found to be effective but are generally considered unpalatable and therefore poorly tolerated. Since the 1990s statin trials have been carried out among children with familial hypercholesterolemia (aged 7 to 17 years), and statins reduced their serum low-density lipoprotein cholesterol levels by 23% to 40%. The safety of statins among children is not well known even though statins seem to be safe and well-tolerated in adults. OBJECTIVES: To assess the effectiveness and safety of statins in children with familial hypercholesterolemia. SEARCH STRATEGY: Relevant trials were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of most recent search: 11 March 2010. SELECTION CRITERIA: Randomized and controlled clinical trials including participants up to 18 years old comparing a statin to placebo or to diet alone. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion and extracted data. MAIN RESULTS: We found 19 potentially eligible studies of which we included eight randomized placebo-controlled trials (897 participants). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points. There was no difference between serum aspartate and alanine aminotransferase as well as creatine kinase concentrations at any time-point. The risks of myopathy and clinical adverse events were also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilation of the brachial artery. AUTHORS' CONCLUSIONS: Statin treatment is an efficient lipid-lowering therapy in children with familial hypercholesterolemia. It seems to be safe in the short term but long-term safety is unknown. Children treated with statins should be carefully followed up by their pediatricians. Large long-term randomized controlled trials are needed to establish the long-term safety of statins.

Statins and cancer: A systematic review and meta-analysis.

BACKGROUND: Systematic reviews on the association between statin therapy and cancer have focused on randomised trials without assessing the quality of evidence. We aimed to review the overall evidence taking study quality into consideration. METHODS: Publications of original studies on the effect of statin treatment on cancer in adult patients were searched on MEDLINE, EMBASE and CENTRAL databases upto October 2007. Our search yielded 37 eligible original studies out of 3607 references. Five studies were additionally found through manual search. Thus, 42 studies were included in the analyses: 17 randomised controlled trials, 10 cohort studies, and 15 case-control studies. FINDINGS: Statins had no effect on the overall incidence of cancer (median risk ratio (RR) 0.96, range 0.72 to 1.2), or on the incidence of lung (median RR 0.92, range 0.83 to 3.0), breast (median RR 1.04, range 0.74 to 19) or prostate cancer (median RR 0.96, range 0.33 to 1.7). They seemed to protect from stomach (median RR 0.59, range 0.40 to 0.88) and liver cancer (median RR 0.62, range 0.33 to 1.2), and from lymphoma (median RR 0.74, range 0.28 to 2.2). They increased the incidence of both melanoma (median RR 1.5, range 1.3 to 1.7) and non-melanoma skin cancer (median RR 1.6, range 1.2 to 2.2). The effect varied, yet inconsistently, by statin type. The median follow-up time was 4 years. The strength of evidence was mostly weak. INTERPRETATION: The evidence suggests that statins do not have short-term effects on cancer risk. The evidence on potentially protective or harmful effects is inconclusive. High quality cohort studies with long follow-up are needed to resolve the issue.

The Pyhäjärvi Cataract Study. I. Study design, baseline characteristics and the demand for cataract surgery.

PURPOSE: The Pyhäjärvi Cataract Study aims to study demand for cataract surgery in the population of a rural town in Finland. METHODS: A random, population-based sample of 881 persons aged > or = 60 years were interviewed by telephone to obtain a Visual Function-14 (VF-14) score. A total of 294 persons were invited for an ophthalmic examination based on three categories of VF-14 score. Of these, 230 (78%) responded, 10 of whom were excluded as a result of prior bilateral surgery. The New Zealand Priority Criteria (NZPC) and the 15-Dimension Quality of Life (15-D) instruments were administered. In addition, another group of 96 patients waiting for cataract surgery were examined and scored using the VF-14, NZPC and 15-D instruments. A modified Lens Opacities Classification System (LOCS) III classification was used for grading the cataract. RESULTS: Only one (0.5%) of the 220 examined subjects was referred for cataract surgery. Many patients with relatively good visual acuity (VA), including six people with a 100-point VF-14 score suggesting no visual symptoms, were waiting for surgery. Demographic factors were not associated with access to cataract surgery. The patients examined from the waiting list for cataract surgery had more cataractous changes in the lens(es), poorer VA, were older, and scored higher on the NZPC instrument than the population sample examined. CONCLUSIONS: Practically no hidden demand for cataract surgery was found in the study population as defined by the national criteria for cataract surgery in Finland. This reflects the fact that the current Finnish health care system appears to recognize and treat cataract patients very well, even in rural areas. Although VA tests may not be sufficient for evaluating need for cataract surgery, the role of questionnaires is not clear either.