Physical signs and atherosclerotic cardiovascular disease in familial hypercholesterolemia: the HELLAS-FH Registry.

AIMS: Three physical signs, namely tendon xanthomas, corneal arcus and xanthelasma, have been associated with heterozygous familial hypercholesterolemia (heFH). The prevalence and clinical significance of these signs are not well established among contemporary heFH individuals. This study explored the frequency as well as the association of these physical signs with prevalent atherosclerotic cardiovascular disease (ASCVD) in heFH individuals. METHODS: Data from the Hellenic Familial Hypercholesterolemia Registry were applied for this analysis. The diagnosis of heFH was based on the Dutch Lipid Clinic Network Score. Multivariate logistic regression analysis was conducted to examine the association of heFH-related physical signs with prevalent ASCVD. RESULTS: Adult patients ( n  = 2156, mean age 50 ±â€Š15 years, 47.7% women) were included in this analysis. Among them, 14.5% had at least one heFH-related physical sign present. The prevalence of corneal arcus before the age of 45 years was 6.6%, tendon xanthomas 5.3%, and xanthelasmas 5.8%. Among physical signs, only the presence of corneal arcus before the age of 45 years was independently associated with the presence of premature coronary artery disease (CAD). No association of any physical sign with total CAD, stroke or peripheral artery disease was found. Patients with physical signs were more likely to receive higher intensity statin therapy and dual lipid-lowering therapy, but only a minority reached optimal lipid targets. CONCLUSION: The prevalence of physical signs is relatively low in contemporary heFH patients. The presence of corneal arcus before the age of 45 years is independently associated with premature CAD.

Prevalence and associated factors of corneal arcus in the geriatric population; Tehran geriatric eye study.

PURPOSE: To determine the age and sex-standardized prevalence of corneal arcus and its associated factors in a geriatric population. METHODS: This population-based cross-sectional study was conducted in 2019 in Tehran; the capital of Iran, using a multi-stage stratified random cluster sampling method. All participants underwent a detailed interview, blood pressure measurement, laboratory blood tests, and a complete ocular examination. RESULTS: Three thousand three hundred ten of 3791 invitees participated in the study (response rate: 87.31%). The mean age of the participants was 69.35 ± 7.62 years (60-97 years) and 1912 (57.76%) were female. Overall, the age and sex-standardized prevalence (95% CI) of corneal arcus was 44.28% (41.21-47.39). Based on the multiple logistic regression, the odds of corneal arcus were higher in men than in women (OR: 1.51; 95% CI: 1.14-2.00); in the age group ≥ 80 years compared to the age group 60-64 years (OR: 2.44; 95% CI: 1.68-3.53), and in retired people compared to employed individuals (OR: 2.05; 95% CI: 1.31-3.21). CONCLUSION: The present study showed a high prevalence of corneal arcus in the geriatric population. Although various studies have reported a significant relationship between corneal arcus with blood lipid and glucose levels as well as blood pressure, these relationships were not found in the present study.

Prevalence of corneal arcus and associated factors in a German population-Results from the Gutenberg Health Study.

PURPOSE: We aimed to determine the prevalence of corneal arcus and to identify associated factors in the general population of Germany. METHODS: The Gutenberg Health Study (GHS) is a population-based cohort study in Germany, which includes an ophthalmological assessment. Refraction, distance-corrected visual acuity, non-contact tonometry and anterior segment imaging were performed for the five-year follow-up examination. Anterior segment photographs were graded for the presence of corneal arcus. Prevalence estimates were computed, and multivariable logistic regression analysis was applied to determine associated factors for corneal arcus including sex, age, spherical equivalent, central corneal thickness, intraocular pressure (IOP), socio-economic status, smoking, BMI, systolic and diastolic arterial blood pressure, HbA1c, HDL-C, LDL-C, triglyceride, and lipid modifying agents. RESULTS: A total of 9,850 right and 9,745 left eyes of 9,858 subjects (59.2±10.8 years), 49.0% females were included in this cross-sectional analysis. 21.1% of men (95%-CI: 20.0%- 22.3%) had a corneal arcus in at least one eye, and 16.9% (95%-CI: 15.9%- 18.0%) of women. In multivariable analyses, the presence of corneal arcus was associated with male gender (OR = 0.54 for female, p<0.0001), higher age (OR = 2.54 per decade, p<0.0001), smoking (OR = 1.59, p<0.0001), hyperopia (OR = 1.05 per diopter, p<0.0001), thinner cornea (OR = 0.994 per µm, p<0.0001), higher IOP (OR = 1.02, p = 0.039), higher HDL-C-level (OR = 2.13, p<0.0001), higher LDL-C-level (OR = 1.21, p<0.0001), and intake of lipid modifying agents (OR = 1.26, p = 0.0001). Arcus was not associated with socio-economic status, BMI, arterial blood pressure, and HbA1c. CONCLUSIONS: Corneal arcus is a frequent alteration of the cornea in Germany and is associated with ocular parameters and systemic parameters of dyslipidemia.

Supravalvular Aortic Stenosis and the Risk of Premature Death Among Patients With Homozygous Familial Hypercholesterolemia.

Patients with homozygous familial hypercholesterolemia (HoFH) have a high risk for premature death. Supravalvular aortic stenosis (SVAS) is a common and the feature lesion of the aortic root in HoFH. The relation between SVAS and the risk of premature death in patients with HoFH has not been fully investigated. The present study analysis included 97 HoFH patients with mean age of 14.7 (years) from the Genetic and Imaging of Familial Hypercholesterolemia in Han Nationality Study. During the median (±SD) follow-up 4.0 (±4.0) years, 40 (41.2%) participants had SVAS and 17 (17.5%) participants experienced death. The proportion of premature death in the non-SVAS and SVAS group was 7.0% and 32.5%, respectively. Compared with the non-SVAS group, SVAS group cumulative survival was lower in the HoFH (log-rank test, p <0.001). This result was further confirmed in the multivariable Cox regression models. After adjusting for age, sex, low density lipoprotein cholesterol (LDL_C)-year-score, lipid-lowering drugs, cardiovascular disease, and carotid artery plaque, SVAS was an independent risk factor of premature death in HoFH on the multivariate analysis (hazard ratio 4.45; 95% confidence interval, 1.10 to 18.12; p = 0.037). In conclusion, a significantly increased risk of premature death was observed in HoFH patients with SVAS. Our study emphasized the importance of careful and aggressive management in these patients when appropriate.

Alcohol consumption, smoking and development of visible age-related signs: a prospective cohort study.

BACKGROUND: Visible age-related signs indicate biological age, as individuals that appear old for their age are more likely to be at poor health, compared with people that appear their actual age. The aim of this study was to investigate whether alcohol and smoking are associated with four visible age-related signs (arcus corneae, xanthelasmata, earlobe crease and male pattern baldness). METHODS: We used information from 11 613 individuals in the Copenhagen City Heart Study (1976-2003). Alcohol intake, smoking habits and other lifestyle factors were assessed prospectively and visible age-related signs were inspected during subsequent examinations. RESULTS: The risk of developing arcus corneae, earlobe crease and xanthelasmata increased stepwise with increased smoking as measured by pack-years. For alcohol consumption, a high intake was associated with the risk of developing arcus corneae and earlobe crease, but not xanthelasmata. CONCLUSIONS: High alcohol consumption and smoking predict development of visible age-related signs. This is the first prospective study to show that heavy alcohol use and smoking are associated with generally looking older than one's actual age.

A population-based study of corneal arcus and its risk factors in Iran.

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.

Corneal arcus and its associations with ocular and general parameters: the Central India Eye and Medical Study.

PURPOSE: To investigate the prevalence of corneal arcus and its associations. METHODS: The Central India Eye and Medical Study was a population-based study performed in rural Central India on 4711 subjects (age, 30+ years). Corneal arcus was assessed in corneal photographs. RESULTS: The study included 952 randomly selected participants. Mean body mass index (BMI) was 19.8 ± 3.6 kg/m(2), with 786 (41.3%) subjects being underweight (BMI < 18.5 kg/m(2)). Corneal arcus of any degree was detected in 102 (10.7% ± 1.0%; 95% CI, 8.8-12.7) subjects. Corneal arcus was significantly associated with increasing age (P < 0.001). It was not significantly (all P > 0.10) associated with serum concentrations of high-density lipoproteins, cholesterol, creatinine, glucose, and glycosylated hemoglobin; with prevalence of arterial hypertension and diabetes mellitus; with body height, weight, and BMI; or with level of education, daily activities, nutrition, alcohol consumption, smoking, and blood pressure. In an intereye comparison, corneal arcus was significantly more marked in the eye with lower intraocular pressure (P = 0.006), thinner central cornea (P = 0.005), and more hyperopic refractive error (P = 0.003). CONCLUSIONS: In this adult rural Central Indian population with low mean BMI, the prevalence of corneal arcus was 10.7% ± 1.0%. The only systemic parameter associated with corneal arcus was increasing age (P < 0.001). Corneal arcus was not associated with dyslipidemia, diabetes mellitus, arterial hypertension, alcohol consumption, or smoking. In this population with low BMI, corneal arcus was not a clinical biomarker for major metabolic disorders. The intereye associations between corneal arcus and low intraocular pressure, thin central cornea, and hyperopia may be of importance in the ophthalmic examination.

Xanthelasmata, arcus corneae, and ischaemic vascular disease and death in general population: prospective cohort study.

OBJECTIVE: To test the hypothesis that xanthelasmata and arcus corneae, individually and combined, predict risk of ischaemic vascular disease and death in the general population. DESIGN: Prospective population based cohort study. SETTING: The Copenhagen City Heart Study. PARTICIPANTS: 12,745 people aged 20-93 years free of ischaemic vascular disease at baseline and followed from 1976-8 until May 2009 with 100% complete follow-up. MAIN OUTCOME MEASURES: Hazard ratios for myocardial infarction, ischaemic heart disease, ischaemic stroke, ischaemic cerebrovascular disease, and death; odds ratios for severe atherosclerosis. RESULTS: 563 (4.4%) of participants had xanthelasmata and 3159 (24.8%) had arcus corneae at baseline. During 33 years' follow-up (mean 22 years), 1872 developed myocardial infarction, 3699 developed ischaemic heart disease, 1498 developed ischaemic stroke, 1815 developed ischaemic cerebrovascular disease, and 8507 died. Multifactorially adjusted hazard/odds ratios for people with versus those without xanthelasmata were 1.48 (95% confidence interval 1.23 to 1.79) for myocardial infarction, 1.39 (1.20 to 1.60) for ischaemic heart disease, 0.94 (0.73 to 1.21) for ischaemic stroke, 0.91 (0.72 to 1.15) for ischaemic cerebrovascular disease, 1.69 (1.03 to 2.79) for severe atherosclerosis, and 1.14 (1.04 to 1.26) for death. The corresponding hazard/odds ratios for people with versus those without arcus corneae were non-significant. In people with versus those without both xanthelasmata and arcus corneae, hazard/odds ratios were 1.47 (1.09 to 1.99) for myocardial infarction, 1.56 (1.25 to 1.94) for ischaemic heart disease, 0.87 (0.57 to 1.31) for ischaemic stroke, 0.86 (0.58 to 1.26) for ischaemic cerebrovascular disease, 2.75 (0.75 to 10.1) for severe atherosclerosis, and 1.09 (0.93 to 1.28) for death. In all age groups in both women and men, absolute 10 year risk of myocardial infarction, ischaemic heart disease, and death increased in the presence of xanthelasmata. The highest absolute 10 year risks of ischaemic heart disease of 53% and 41% were found in men aged 70-79 years with and without xanthelasmata. Corresponding values in women were 35% and 27%. CONCLUSION: Xanthelasmata predict risk of myocardial infarction, ischaemic heart disease, severe atherosclerosis, and death in the general population, independently of well known cardiovascular risk factors, including plasma cholesterol and triglyceride concentrations. In contrast, arcus corneae is not an important independent predictor of risk.

Effect of corneal arcus on central corneal thickness, intraocular pressure, and primary open-angle glaucoma: the Singapore Malay Eye Study.

OBJECTIVES: To examine the association of corneal arcus with central corneal thickness (CCT), intraocular pressure (IOP), and the prevalence of primary open-angle glaucoma. METHODS: This was a population-based cross-sectional study of Malay participants aged 40 to 80 years living in Singapore. Participants underwent a standardized interview and systemic and ocular examinations, including CCT, IOP, and corneal curvature radius measurements. Corneal arcus, assessed using a slitlamp, was defined as gray-white or yellow opacity located near the periphery of the cornea but separated from the limbus by a clear zone. RESULTS: Corneal arcus was found in right eyes among 1747 (57.9%) of 3015 participants. After adjusting for age, sex, and systemic factors, IOP was higher (15.87 vs 14.86 mm Hg, P < .001) and CCT was thinner (540.6 vs 543.4 µm, P = .03) in eyes with vs without corneal arcus. In multiple linear regression models, eyes with corneal arcus had on average 1.14 mm Hg higher IOP than eyes without corneal arcus. In the presence of corneal arcus, the linear correlations of CCT × IOP and of corneal curvature radius × IOP were altered. The prevalence of ocular hypertension, but not primary open-angle glaucoma, was significantly higher among participants with corneal arcus than among participants without corneal arcus (P = .02). CONCLUSIONS: Corneal arcus was associated with higher IOP and lower CCT independent of age, sex, and systemic and ocular factors. Further research is required to investigate the clinical implications of these findings for IOP assessment in eyes with corneal arcus.

Moderate phenotypic expression of familial hypercholesterolemia in Tunisia.

BACKGROUND: Autosomal Dominant Hypercholesterolemia (ADH) is an autosomal dominant disease caused by mutations in the low density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Xanthomas and coronary heart diseases (CHD) at an early age are the major clinical manifestations of the disease. METHODS: 16 families with familial hypercholesterolemia from different regions in Tunisia participated in the study. Mutations within the LDLR gene were screened through DNA sequencing. Lipids values were measured by standard enzymatic methods. RESULTS: We present here thirty five homozygotes and fifty six heterozygotes. Homozygotes presented extensive xanthomatosis, variable clinical manifestations of CHD, and total cholesterol levels in males and females of 17.26+/-4.18 and 17.64+/-2.59 mmol/L respectively. HDL-cholesterol levels were 0.62+/-0.24 and 1.00+/-0.61 mmol/L for males and females, respectively. None of the heterozygotes had tendon xanthomas (except for one female aged 62), eight had corneal arcus, and nine developed CHD mean between 46 and 88 years old. Total cholesterol levels in males and females ranged from 4.60 to 8.90 and from 4.30 to 10.50 mmol/L, respectively. CONCLUSION: Tunisian FH heterozygotes are characterized by a moderate clinical and biological expression of the disease.

Corneal arcus and cardiovascular risk factors in middle-aged subjects in Taiwan.

BACKGROUND: To delineate the association between corneal arcus and potential cardiovascular risk factors in middle-aged population. METHODS: This cross-sectional study randomly enrolled 119 subjects with corneal arcus and 119 subjects without arcus, aged between 30 and 60 years, from community-based East Asian population. Corneal arcus identification was completed by a single ophthalmologist using slit-lamp biomicroscopy examination. Cardiovascular risk factor parameters were measured by standardized techniques. RESULTS: Subjects with higher levels of total-cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and total/HDL cholesterol ratio had increased risk of having corneal arcus, whereas subjects with higher systolic blood pressure (SBP) and diastolic blood pressure had decreased risk. Using stepwise logistic regression analysis, we found that male gender was a strong independent risk factor for arcus formation [odds ratio (OR): 2.87; 95% confidence interval (CI): 1.59-5.17; P < 0.001]. Higher non-HDL-C level also had significant but mildly increased risk (OR: 1.02; 95% CI: 1.01-1.02; P 0.008) of having arcus, whereas higher SBP had significant but mildly decreased risk (OR: 0.98; 95% CI: 0.96-0.99; P < 0.001). Besides, subjects who had circumferential arcus had significantly higher risk of having LDL-C >or=160 mg/dL than those who had only partial arcus (OR: 5.79 versus OR: 4.60; P < 0.001). CONCLUSIONS: In addition to serum LDL-C, male gender and serum non-HDL-C level are significantly correlated to corneal arcus. Conversely, SBP is negatively correlated to corneal arcus. Presence of corneal arcus in middle-aged men may be an indicator for dyslipidemia, and we speculate that the relationship between arcus and coronary heart disease may be dependent of dyslipidemia.

Relation of corneal arcus to cardiovascular disease (from the Framingham Heart Study data set).

Corneal arcus is a lipid-rich deposit at the corneoscleral limbus that shares some similarities with the lipid deposition of atherosclerosis. Epidemiologic studies examining the association between corneal arcus and coronary artery disease (CAD) have yielded mixed results. This study was conducted to determine if corneal arcus is an independent risk factor for cardiovascular disease (CVD) and CAD. A prospective analysis was performed using Cox proportional-hazards regression models in the Framingham Heart Study Original Cohort and Offspring Cohort database. This cohort included 23,376 patient-examinations, during 3,890 (17%) of which corneal arcus was identified. Corneal arcus was a predictor of CVD and CAD at 4 years (hazard ratios [HRs] 2.28 and 1.99, respectively) and 8 years (HRs 2.52 and 2.35, respectively) of follow-up (p <0.0001 for all). Corneal arcus was no longer predictive of either CVD or CAD, however, after adjustment for age and gender at 4 years (HRs 1.07 and 1.01, respectively) and 8 years (HRs 1.18 and 1.17, respectively) of follow-up (p >0.05 for all). In conclusion, corneal arcus predicted CVD and CAD in the community-based Framingham Heart Study cohort because of the strong association of corneal arcus with increasing age. To date, this is the largest and lengthiest population-based cohort study examining the direct association between corneal arcus and CVD and CAD.

Familial hypercholesterolaemia: the Cape Town experience.

Familial hypercholesterolaemia (FH), an autosomal dominantly inherited disorder characterised by elevated plasma low-density lipoprotein (LDL) cholesterol levels, tendon xanthomata and premature ischaemic heart disease, is amenable to treatment with modern medication. The clinical and biochemical details of 1 031 patients with FH were analysed. FH is the most common monogenic disorder of lipoprotein metabolism presenting to the Lipid Clinic at Groote Schuur Hospital, accounting for about 20% of consultations. The hospital classified 55% of the FH patients as white, 43% as coloured, 1.5% as Asian and 0.5% as black. In the FH cohort (whose mean age at presentation was 44 years), 80% had tendon xanthomata, 36% had arcus cornealis, and 14% had xanthelasma. Tendon xanthomata was present in almost 90% of patients by the age of 50 years. Arcus cornealis was present in about 45% by the age of 40 years, further increasing in frequency with age. Cardiovascular complications included ischaemic heart disease (43%), stroke (1.5%), transient ischaemic attacks (1.3%), and peripheral vascular disease (3.7%). The mean age of death was 55 (+/-13) years; 51 ( +/-10) years in men and 61 ( +/-12) years in women. In 46% of the cohort, a defective gene was identified by testing for locally prevalent mutations.

Serum lipid parameters and the prevalence of corneal arcus in a dyslipidaemic patient population.

AIM: To determine whether an association exists between plasma lipoprotein constituents and the prevalence of corneal arcus in dyslipidaemic patients. METHODS: Adult patients (n = 115) were included if their fasting total serum cholesterol concentrations exceeded the 95th percentile or their serum low-density lipoprotein (LDL) : high density lipoprotein (HDL) ratios exceeded 5. Slit-lamp assessment of the corneas was performed. RESULTS: The study group divided into a subgroup with arcus 37% (43) and a subgroup without arcus 63% (72). Total serum cholesterol and triglyceride levels were not associated with corneal arcus. A significant difference was found (p < 0.05) between the mean levels of LDL cholesterol (LDL-C) in the group without arcus (5.61 +/- 1.74 mmol/l) and the group with arcus (5.96 +/- 1.71 mmol/l). The mean serum HDL-cholesterol (HDL-C) in the group with corneal arcus was 1.04 +/- 0.30 mmol/l as opposed to 1.31 +/- 0.38 mmol/l in the group without arcus (p < 0.005 for difference). The mean LDL-C : HDL-C ratio in the group without arcus was 4.28 (SD: 1.99), and 5.73 (SD: 2.09) in the group with a corneal arcus (p < 0.05). CONCLUSIONS: Low HDL-C levels, high LDL-C levels and LDL-C : HDL-C ratios > 5 have been implicated as risk factors of numerous circulatory diseases. The observations in this study suggest that the presence of corneal arcus in the dyslipidaemic patient correlates strongly with these same risk indicators.

Corneal arcus associated with dyslipidemia.

A cross sectional study based on 243 subjects with an age range of 20-63 years, was conducted to assess the prevalence of corneal arcus and the association between corneal arcus and dyslipidemia which is a coronary heart disease risk factor. The presence of corneal arcus was determined by hand-held slitlamp, serum lipids and serum plasma glucose collected on the same day as corneal arcus detection. Total cholesterol (CHOL), triglyceride (TG) and high density lipoprotein (HDL) were measured by enzymatic procedure, and low density lipoprotein (LDL) was estimated by the Friedewald formula. The prevalence of corneal arcus was divided into 3 age groups, 20-29 years (0%), 30-49 years (male 41.5%, female 26.13%) and 50-69 years (male 86.2%, female 59.1%) In the 30-49 year, female group, those with corneal arcus had higher serum LDL and total cholesterol concentration than those without corneal arcus. The mean difference of LDL was 22.21 mg/dl (p=0.001) and total cholesterol was 30.95 mg/dl (p=0.000). In the 30-49 year, male group people with corneal arcus had a lower serum HDL concentration than those without corneal arcus and the mean difference of the HDL was 8.6 mg/dl (p=0.014). There was no difference for corneal arcus and serum lipid in the 50-69 years group in both sexes. No association between corneal arcus and fasting plasma glucose was found in all ages and both sexes. It is concluded that while corneal arcus is primarily an aged-related change, if present in people under 50 years it should be considered for dyslipidemia which is one of the risk factors for coronary heart disease.

Latent model for correlated binary data with diagnostic error.

We propose a methodology for modeling correlated binary data measured with diagnostic error. A shared random effect is used to induce correlations in repeated true latent binary outcomes and in observed responses and to link the probability of a true positive outcome with the probability of having a diagnosis error. We evaluate the performance of our proposed approach through simulations and compare it with an ad hoc approach. The methodology is illustrated with data from a study that assessed the probability of corneal arcus in patients with familial hypercholesterolemia.

[Corneal arcus and life expectancy]. / Arcus corneae és élettartam.

In 1964-66, the authors completed the comprehensive medical screening of 1412 persons. Apart from the indicators of health state they also recorded their social and cultural parameters. The diagnoses they registered included AC, which has been covered in literature in rather contradicting ways. They found no data concerning survival; as analysing such a correlation is only possible within the frame-work of a several-decade follow-up study. By the end of the follow-up stage (31:12:1994), after 30 years, 1375 persons had died. Their death certificates and--if there were any--necropsy records have been processed and thoroughly analysed. They examined the occurrence of AC, life duration and survival probability--all in correlation with age, gender, constitution, certain diseases (hypertonia, ostheoarthrosis) and diagnoses at death (ischaemic heart diseases, acute myocardiac infarction, cerebrovascular diseases). They point it out that the occurrence of AC is significantly higher among males, but it increases in strong correlation with age in both sexes. Those who had AC were found to be older at the time of death, but it doesn't mean that AC correlates with better life expectancy--it means that AC occurs at older age. The survival probability of men over 75 was better than that of women. On the whole, AC is unfavourable concerning life expectancy, but the later it occurs, the less it can be used as an indicator of life expectancy. It was found that greater average weight correlated with longer average life duration, while among females the more a person weighed, the less frequent AC became. It was true for each weight group that those with AC had worse life expectancy. Altogether those with no AC were found to suffer from hypertonia significantly more frequently. The life expectancy of those with both AC and hypertonia, however, was always worse than those with hypertonia only, regardless of age and the type of hypertonia. Generally women are in a more favourable position, but in the 'serious' and 'very serious' hypertonia groups there is practically no difference in the survival of the two sexes. The authors have also found that AC has a significant negative prognostical value concerning survival and correlation with ostheoarthrosis, ischaemic heart diseases and cerebrovascular diseases. The correlation of AC with acute myocardiac infarction could not be proved convincingly.

Corneal arcus, case finding and definition of individual clinical risk in heterozygous familial hypercholesterolaemia.

Premature corneal arcus may identify individuals with hyperlipidaemia and increased cardiovascular risk. We have attempted to quantitate relationships through determination of graded prevalence of corneal arcus with age for 81 males and 73 females suffering from heterozygous familial hypercholesterolaemia (HFH) at presentation, and for 280 male and 353 female unselected patients (age range 16-76 years) attending a country general practice. Some degree of arcus affected 50% of HFH patients by age 31-35 years, and 50% of practice patients by age 41-45 years. Complete full ring arcus affected 50% of the familial hypercholesterolaemia (FH) group by age 50 years, with only 5% similarly affected in the non-FH group. Arcus grade with age was advanced by some 5 years in males versus females. Premature arcus potentially alerting to HFH can be broadly defined for males and females combined, as heavy full ring by age 50 years, or any degree of arcus by age 30-35 years. Arcus grade was not related to the presence of coronary disease. Accelerated development of corneal arcus with age is an indicator of HFH, but premature arcus is not an additional marker of premature coronary disease for individual cases of HFH.

A novel single base deletion in the LDLR gene (211delG): Effect on serum lipid profiles and the influence of other genetic polymorphisms in the ACE, APOE and APOB genes.

A single base deletion (211delG) in the low density lipoprotein receptor (LDLR) gene was shown to cause familial hypercholesterolaemia (FH) in a large family from Northern Ireland. Twenty-four of 52 family members tested had this mutation, 13 of which were newly diagnosed. Mutation-positive individuals had significantly higher mean total-cholesterol (TC) and LDL-cholesterol (LDL-C) than those without 211delG. LDL-C was a more accurate indicator of disease status than TC. When TC levels alone were considered, in individuals over 16 years, a false negative rate (TC < 7.5 mmol/l) of 40% was found; however this fell to 13% based on inclusion of LDL-C levels. Individuals with coronary artery disease (CAD) had significantly higher TC levels than those without CAD and tended to have tendinous xanthomas (TX) and corneal arcus (CA). Generic polymorphisms in the angiotensin converting enzyme (ACE) and apolipoprotein (apo) B genes did not appear to be associated with lipid levels or with the clinical severity of the disease; however, the apo E epsilon4 allele did show a lipid-raising effect in individuals with the mutation.

Corneal arcus and cardiovascular risk factors in Asians in Singapore.

This study was a cross-sectional random survey of the whole of Singapore, based on 2143 subjects (aged 18-69 years, response rate 60.3%). The presence of corneal arcus was determined by a doctor using the naked eye in good light. Cardiovascular risk factors were measured by standardized techniques. The prevalence rates overall of corneal arcus were: 18-29 years (males 0.5%, females 0.3%), 30-49 years (males 18.1%, females 13.3%) and 50-69 years (males 70.7%, females 55.3%). In the 30-49 age group, people with arcus had higher serum low density lipoprotein (LDL) cholesterol concentrations than people without arcus, the mean differences being, males 0.31 mmol/l (P = 0.040) and females 0.62 mmol/l (P less than 0.001) with an increased likelihood of having values greater than 5.5.mmol/l of males 1.8 (95% confidence interval (95% CI): 1.0-3.4) and females 2.6 (95% CI: 1.4-4.8). There were no significant differences for LDL-cholesterol in the 50-69 age group. Arcus was weakly associated with fasting plasma glucose in the 30-49 age group. Arcus was not associated with serum high density lipoprotein (HDL) cholesterol, serum fasting triglyceride, blood pressure and cigarette smoking. It is concluded that while corneal arcus is primarily an age-related change, its formation is accelerated by high serum LDL-cholesterol so that in people under 50 years it is a marker for the condition.