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Atherosclerosis Aug 2017There is controversy on the accuracy of different diagnostic criteria for familial hypercholesterolemia (FH). The aim of this study is to assess the performance of... (Comparative Study)
Comparative Study
BACKGROUND AND AIMS
There is controversy on the accuracy of different diagnostic criteria for familial hypercholesterolemia (FH). The aim of this study is to assess the performance of different clinical criteria used to identify individuals for FH genetic cascade screening in Brazil.
METHODS
All index cases (IC) registered in the Hipercol Brasil program between 2011 and 2016 were analyzed. Inclusion criteria were age ≥18 years and elevated LDL-cholesterol (LDL-C) levels, with a conclusive result in the genetic test, whether positive or negative. Initially, we tested the multivariable association between clinical and laboratory markers and the presence of an FH causing mutation. Then, we analyzed sensitivity, specificity, positive and negative predictive values for the LDL-C quartile distribution, LDL-C as a continuous variable, as well as the performance measures for the Dutch Lipid Clinic Network (DLCN) score to identify a mutation.
RESULTS
Overall, 753 ICs were included and an FH causing mutation was found in 34% (n = 257) of the subjects. After multivariable analysis, LDL-C as a continuous variable, tendon xanthomas and corneal arcus were independently associated with the presence of FH mutations. LDL-C values ≥ 230 mg/dL (5.9 mmol/L) had the best tradeoff between sensitivity and specificity to diagnose a mutation. The DLCN score presented a better performance than LDL-C to identify a mutation, area under the ROC curve were 0.744 (95% CI: 0.704-0.784) and 0.730 (95% CI: 0.687-0.774), respectively, p=0.014.
CONCLUSIONS
In our population, LDL ≥230 mg/dL is a feasible criterion to indicate ICs to genetic testing.
Topics: Adult; Aged; Arcus Senilis; Area Under Curve; Biomarkers; Brazil; Chi-Square Distribution; Cholesterol, LDL; Clinical Decision-Making; DNA Mutational Analysis; Feasibility Studies; Female; Genetic Predisposition to Disease; Genetic Testing; Humans; Hyperlipoproteinemia Type II; Logistic Models; Male; Middle Aged; Multivariate Analysis; Mutation; Patient Selection; Phenotype; Predictive Value of Tests; ROC Curve; Reproducibility of Results; Risk Factors; Up-Regulation; Xanthomatosis
PubMed: 28689098
DOI: 10.1016/j.atherosclerosis.2017.06.917 -
Journal of Cardiovascular Pharmacology Mar 2017The Hypertension Community has 3 conflicting dilemmas: a goal systolic pressure of 120 mm Hg or less (the SPRINT Trials), 40% of our 60,000,000 hypertensives still... (Review)
Review
UNLABELLED
The Hypertension Community has 3 conflicting dilemmas: a goal systolic pressure of 120 mm Hg or less (the SPRINT Trials), 40% of our 60,000,000 hypertensives still sustain blood pressures above 140/90 mm Hg, and our most potent antihypertensive drug minoxidil sits on the sidelines, imprisoned in the Food and Drug Administration's Black Box designation. My solutions to these dilemmas are: (1) review of the facts of our most potent antihypertensive drug minoxidil which is essentially free of toxicity, (2) treatment focus on the fundamental cause of high blood pressure, that is excess dietary sodium and, (3) prevention of, and/or reversal of, the fundamental mechanism of worsening hypertension, arteriolar hypertrophy.
SUMMARY
The Hypertension Community has 3 conflicting dilemmas: a goal systolic pressure of 120 mm Hg or less (the SPRINT Trials), 40% of our 60,000,000 hypertensives still sustain blood pressures above 140/90 mm Hg, and our most potent antihypertensive drug minoxidil sits on the sidelines, imprisoned in the Food and Drug Administration's Black Box designation. My solutions to these dilemmas are: (1) review of the facts of our most potent antihypertensive drug minoxidil which is essentially free of toxicity, (2) treatment focus on the fundamental cause of high blood pressure (HBP) and excess dietary sodium and, (3) prevention of, and/or reversal of, the fundamental mechanism of worsening hypertension, arteriolar hypertrophy. My focus at UT Southwestern in Dallas was on extremely severely hypertensive patients with a quantifiable, measurable complication of HBP, progression of nephrosclerotic damage to kidneys. This model had the greatest likelihood of exposing fundamental disregulatory mechanisms in hypertensive patients (which it did) and the potential for study of the most relevant antihypertensive drug interactions to achieve optimal blood pressure control (which it did). By maintaining diastolic pressures at 80 mm Hg or less in the first National Institutes of Health-supported, long-term randomized clinical trial to save the kidneys, the bases for a fundamental blood pressure support mechanism (arteriolar hypertrophy) was illuminated but not fully described until now. This fundamental hypertensinogenic mechanism results from HBP but with time and severity, becomes its own raison d'être. I am now aged 84 years. As a result of a stroke 20 years ago, which caused permanent double vision, and because of poor blood pressure control with triple therapy, I started using minoxidil 5 mg/d along with atenolol and occasional furosemide. Now, along with some dietary salt restriction, my resting blood pressure is 110/65-125/75 and, despite >30 years history of HBP, I have no retinal arteriolar hypertrophy nor arcus senilis (Dr. Schwartz-U. of Miami) which is almost universally present at this age. Yes, prevention of, or reversal of, arteriolar hypertrophy should be a central focus of HBP treatment. I simply wish to share a bit of accumulated wisdom that might be of use to others.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Humans; Hypertension; Kidney; Minoxidil; Sodium Chloride, Dietary
PubMed: 28267687
DOI: 10.1097/FJC.0000000000000458 -
Cornea Jul 2016To compare the corneal biomechanical properties and intraocular pressure (IOP) levels in patients with and without arcus senilis (AS). (Comparative Study)
Comparative Study
PURPOSE
To compare the corneal biomechanical properties and intraocular pressure (IOP) levels in patients with and without arcus senilis (AS).
METHODS
Ocular response analyzer measurements were performed on the right eyes of 37 patients with AS (group 1) and 37 control eyes (group 2). Corneal hysteresis, corneal resistance factor, Goldmann-correlated IOP, and corneal compensated IOP were recorded with Ocular response analyzer. Spherical equivalent value of the refractive errors, axial length, central corneal thickness, and IOP measured with Goldmann applanation tonometer were noted for each study eyes. Statistical analyses were performed with Student t, Kruskal-Wallis, and Pearson correlation tests.
RESULTS
Mean age was 67.6 ± 9.8 years in group 1 and 65.3 ± 8.1 years in group 2 (P = 0.308). Mean corneal hysteresis and corneal resistance factor readings were 9.8 ± 0.9 versus 10.6 ± 0.8 (P < 0.001) and 10.05 ± 1.07 versus 10.9 ± 0.9 (P < 0.001) in groups 1 and 2, respectively. Mean corneal compensated IOP and Goldmann-correlated IOP values were found as 16.1 ± 3.3 mm Hg versus 15.8 ± 2.6 mm Hg (P = 0.719) and 15.1 ± 3.3 mm Hg versus 15.0 ± 2.6 mm Hg (P = 0.912) in groups 1 and 2, respectively. There was no statistical difference in IOP measured with Goldmann applanation tonometer, central corneal thickness, spherical equivalent value of the refractive error, axial length measurements, and mean keratometry readings between the 2 groups (P = 0.983, P = 0.289, P = 0.938, P = 0.886, P = 0.07, respectively).
CONCLUSIONS
The mean corneal hysteresis and corneal resistance factor values of eyes with AS were lower when compared with the controls. This study demonstrated that AS may change the corneal biomechanical properties.
Topics: Aged; Aged, 80 and over; Arcus Senilis; Axial Length, Eye; Biomechanical Phenomena; Cornea; Elasticity; Female; Humans; Intraocular Pressure; Male; Middle Aged; Prospective Studies; Tonometry, Ocular; Visual Acuity
PubMed: 27124777
DOI: 10.1097/ICO.0000000000000856 -
Arteriosclerosis, Thrombosis, and... Jan 2016Patients with familial hypercholesterolemia (FH) are at high risk for premature atherosclerotic cardiovascular disease (ASCVD), especially because of long-term exposure...
OBJECTIVE
Patients with familial hypercholesterolemia (FH) are at high risk for premature atherosclerotic cardiovascular disease (ASCVD), especially because of long-term exposure to high low-density lipoprotein cholesterol levels. It has been reported that low-density lipoprotein-lowering therapy delays the onset of ASCVD. However, it still remains difficult to prevent it. Therefore, novel biomarkers and therapeutic targets are necessary to evaluate and prevent atherosclerosis in FH. The aim of this study was to investigate associations of cholesterol efflux capacity with the presence of ASCVD and clinical features in patients with heterozygous FH.
APPROACH AND RESULTS
We measured cholesterol efflux capacity in 227 patients with heterozygous FH under pharmaceutical treatment. Seventy-six (33.5%) of them were known to have ASCVD. In a logistic-regression analysis adjusted for risk factors, increased efflux capacity was associated with decreased risk of ASCVD even after the addition of high-density lipoprotein cholesterol level as a covariate (odds ratio per 1-SD increase, 0.95; 95% confidence interval, 0.90-0.99; P<0.05). Decreased cholesterol efflux capacity was associated with the presence of corneal arcus after adjusting for age and sex. In addition, inverse relationships between cholesterol efflux capacity and Achilles tendon thickness, as well as carotid intima-media thickness, were observed after adjustment for age, sex, and traditional cardiovascular risk factors.
CONCLUSIONS
Cholesterol efflux capacity was independently and inversely associated with the presence of ASCVD in heterozygous FH. In view of residual risks after treatment with statins, cholesterol efflux capacity might be a novel biomarker and a therapeutic target for preventing atherosclerosis in patients with FH.
Topics: Achilles Tendon; Adult; Aged; Arcus Senilis; Asymptomatic Diseases; Atherosclerosis; Biomarkers; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cholesterol, HDL; Cross-Sectional Studies; Female; Genetic Predisposition to Disease; Heterozygote; Humans; Hyperlipoproteinemia Type II; Linear Models; Logistic Models; Male; Middle Aged; Mutation; Odds Ratio; Phenotype; Proprotein Convertase 9; Proprotein Convertases; Radiography; Receptors, LDL; Serine Endopeptidases
PubMed: 26543100
DOI: 10.1161/ATVBAHA.115.306665 -
Journal of Pharmacy & Bioallied Sciences Apr 2015The corneal arcus consists of cholesterol, phospholipids and triglycerides. As serum triglyceride is one of the accurate of lipid metabolic state, greater importance was...
The corneal arcus consists of cholesterol, phospholipids and triglycerides. As serum triglyceride is one of the accurate of lipid metabolic state, greater importance was given, and it was found to be elevated in 72% of patients and a positive correlation with increasing age. This suggests a strong correlation between impairment of lipid metabolism and incidence of corneal arcus.
PubMed: 26015693
DOI: 10.4103/0975-7406.155765 -
Ophthalmic Epidemiology Oct 2014To determine the prevalence of corneal arcus, its risk factors, and its relationship to ocular and visual indices.
PURPOSE
To determine the prevalence of corneal arcus, its risk factors, and its relationship to ocular and visual indices.
METHODS
In this cross-sectional study, 300 clusters were randomly selected from Shahroud in the north of Iran, using multistage sampling. A total of 20 people were invited to participate from each cluster. After enrollment, all optometric, biometric and ophthalmic exams were conducted on site.
RESULTS
Of 6311 people invited, 5190 (82.2%) participated in the study. The prevalence of corneal arcus was 23.3% (95% confidence interval, CI, 22.1-24.6), and 98.4% were bilateral cases. The prevalence of corneal arcus was higher in men (odds ratio, OR, 2.02, 95% CI 1.8-2.3, p < 0.001) and increased with age (OR 1.1/year, p < 0.001). In a multivariable-adjusted regression model, age (OR 1.1/year, p = 0.006), male sex (OR 1.30, p = 0.001), diabetes (OR 0.7, p < 0.001), smoking (OR 1.5, p = 0.003), outdoor activity (OR 1.4, p = 0.006), systolic blood pressure (OR 1.01, p = 0.012), and diastolic blood pressure (OR 0.99, p = 0.016) were significantly correlated with corneal arcus. Including biometric components in another model, corneal thickness (OR 0.99, p < 0.001), anterior chamber depth (OR 0.68, p < 0.001) and corneal radius of curvature (OR 1.59, p < 0.001) were significantly correlated with corneal arcus.
CONCLUSION
This study adds valuable information to the epidemiology of corneal arcus in Iran and the Middle East. In people aged over 60 years, nearly 50% of the study population had corneal arcus. Older age, male sex, smoking, and systolic hypertension were risk factors for corneal arcus. Corneal arcus was also associated with thin and flat corneas and shallow anterior chamber depth.
Topics: Adult; Age Distribution; Aging; Arcus Senilis; Biometry; Cross-Sectional Studies; Female; Humans; Iran; Male; Middle Aged; Prevalence; Risk Factors; Sex Distribution; Sex Factors; Visual Acuity
PubMed: 25118951
DOI: 10.3109/09286586.2014.949782 -
European Heart Journal Aug 2014Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein...
Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society.
AIMS
Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH.
METHODS AND RESULTS
Early diagnosis of HoFH and prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH. We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensive ACVD evaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary.
CONCLUSION
This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH.
Topics: Anticholesteremic Agents; Arcus Senilis; Atherosclerosis; Blood Component Removal; Cardiovascular Diseases; Cholesterol, LDL; Diagnosis, Differential; Early Diagnosis; Gene Frequency; Genetic Heterogeneity; Homozygote; Humans; Hyperlipoproteinemia Type II; Liver Transplantation; Mutation; Pedigree; Phenotype; Practice Guidelines as Topic; Xanthomatosis
PubMed: 25053660
DOI: 10.1093/eurheartj/ehu274 -
Indian Journal of Dermatology,... 2014
Topics: Arcus Senilis; Child; Humans; Hyperlipoproteinemia Type II; Male; Xanthogranuloma, Juvenile
PubMed: 25035360
DOI: 10.4103/0378-6323.136904 -
Ophthalmic Genetics 2015H syndrome is an autosomal recessive histiocytosis with multisystemic involvement caused by mutations in the SLC29A3 gene. The term H syndrome was coined to denote the...
BACKGROUND
H syndrome is an autosomal recessive histiocytosis with multisystemic involvement caused by mutations in the SLC29A3 gene. The term H syndrome was coined to denote the major clinical findings which include hyperpigmentation, hypertrichosis, hearing loss, hepatosplenomegaly, hypogonadism, hyperglycemia/diabetes mellitus and hallux valgus/flexion contractures. Almost 100 individuals affected with this disorder have been reported, however, a thorough evaluation of the ophthalmologic features of H syndrome has not yet been performed.
MATERIALS AND METHODS
Ophthalmic examination of a 50-year-old male with H syndrome. Mutation analysis of SLC29A3 was also performed in this patient.
RESULTS
Ophthalmic findings included; shallow orbits with exorbitism, bilateral pterygium, limbal thickening, corneal arcus and cortical cataract. We also review ophthalmologic findings in previously reported H syndrome patients.
CONCLUSIONS
The presence of dilated lateral scleral vessels, corneal arcus and shallow orbits should raise the suspicion of H syndrome, especially when seen in young age.
Topics: Arcus Senilis; Cataract; Contracture; DNA Mutational Analysis; Exophthalmos; Hearing Loss, Sensorineural; Histiocytosis; Humans; Limbus Corneae; Male; Middle Aged; Nucleoside Transport Proteins; Pterygium; Sclera; Vascular Diseases
PubMed: 24547910
DOI: 10.3109/13816810.2014.886272 -
The Journal of Pediatrics Mar 2014
Topics: Arcus Senilis; Child, Preschool; Humans; Hyperlipoproteinemia Type II; Male
PubMed: 24314439
DOI: 10.1016/j.jpeds.2013.10.045