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.

Acute myocardial infarction in a 28 year man with familial hypercholesterolemia.

Familial hypercholesterolemia is a single gene disorder. It has autosomal dominant pattern of inheritance. We report a 28-year-old man who presented with acute myocardial infarction. He had xanthomas and an elevated serum low density lipoprotein cholesterol (LDL-C). His only sibling, 32-year-old brother have similar cutaneous lesions and lipid profile. His mother and maternal uncle died at a young age due to myocardial infarction. This report is to emphasize the need to clinically recognize xanthomas and its familial inheritance with elevated LDL-C, premature atherosclerosis. Early diagnosis and early initiation of treatment will save the affected individual and the other family members.

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.

Corneal arcus: an indicator of severe coronary artery disease in a young adult man.

A 32-year-old man was transferred to our emergency service with the diagnosis of sudden cardiopulmonary arrest. During eye examination, a typical corneal arcus was observed. The patient underwent the primary percutaneous coronary intervention. Coronary angiography showed a total occlusion of proximal left anterior descending artery. Primary coronary balloon angioplasty was successfully performed. Independently of total cholesterol, serum high-density lipoprotein cholesterol and smoking, corneal arcus has been suggested as a predictor of coronary heart disease among hyperlipidemic men. Physical examination can yield valuable diagnostic clues in a patient suspected of ischaemic heart disease. In summary, the appearance of corneal arcus in young adult men might be an indicator of severe coronary artery disease and should be screened by means of physical examination especially in the setting of cardiopulmonary arrest (Fig. 1, Ref. 4).

Correlating corneal arcus with atherosclerosis in familial hypercholesterolemia.

BACKGROUND: A relationship between corneal arcus and atherosclerosis has long been suspected but is controversial. The homozygous familial hypercholesterolemia patients in this study present a unique opportunity to assess this issue. They have both advanced atherosclerosis and corneal arcus. METHODS: This is a cross-sectional study of 17 patients homozygous for familial hypercholesterolemia presenting to the Clinical Center of the National Institutes of Health. Plasma lipoproteins, circumferential extent of arcus, thoracic aorta and coronary calcific atherosclerosis score, and Achilles tendon width were measured at the National Institutes of Health. RESULTS: Patients with corneal arcus had higher scores for calcific atherosclerosis (mean 2865 compared to 412), cholesterol-year score (mean 11830 mg-yr/dl compared to 5707 mg-yr/dl), and Achilles tendon width (mean 2.54 cm compared to 1.41 cm) than those without. Corneal arcus and Achilles tendon width were strongly correlated and predictive of each other. Although corneal arcus was correlated with calcific atherosclerosis (r = 0.67; p = 0.004), it was not as highly correlated as was the Achilles tendon width (r = 0.855; p < 0.001). CONCLUSION: Corneal arcus reflects widespread tissue lipid deposition and is correlated with both calcific atherosclerosis and xanthomatosis in these patients. Patients with more severe arcus tend to have more severe calcific atherosclerosis. Corneal arcus is not as good an indicator of calcific atherosclerosis as Achilles tendon thickness, but its presence suggests increased atherosclerosis in these hypercholesterolemic patients.

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.

Epithelial iron line in juvenile corneal arcus lipoides.

Iron lines of the corneal epithelium are well-described phenomena in both normal and pathologic conditions. We found a bilateral corneal epithelial iron line at the inner edge of a juvenile corneal arcus lipoides in an otherwise normal eye of a 38-year-old white man. Possible mechanisms that may have led to the development of this new iron line are discussed.

Gerontoxon precoce / Early gerontoxon

Doze casos de gerontoxon precoce säo estudados. É discutida a relaçäo entre os níveis de colesterolemia e lipiolemia no surgimento desta patologia

The association of corneal arcus with coronary heart disease and cardiovascular disease mortality in the Lipid Research Clinics Mortality Follow-up Study.

The relationship between corneal arcus (arcus senilis) and mortality from coronary heart disease (CHD) and cardiovascular disease (CVD) is examined in a prospective study of White men (n = 3,930) and women non-hormone users (n = 2,139), ages 30-69, followed for an average of 8.4 years as part of the Lipid Research Clinics Mortality Follow-up Study. After excluding those with clinically manifest CHD at baseline, corneal arcus was strongly associated with CHD and CVD mortality only in hyperlipidemic men ages 30-49 years, for whom the relative risk for CHD and CVD death was 3.7 and 4.0, respectively, after adjusting for age, total cholesterol, HDL cholesterol, and smoking status using a Cox proportional hazards model. Among 30-49 year old males, corneal arcus appears to be a prognostic factor for CHD, independent of its association with hyperlipidemia in this age-group, of about the same magnitude as other common risk factors, underscoring the usefulness of corneal arcus as a prognostic factor to the practicing clinician.

Association between corneal arcus and some of the risk factors for coronary artery disease.

The relationships between coronary artery disease risk factors and corneal arcus were examined in 150 adults aged 55 years and above of both sexes and from different ethnic origins. The width of the corneal arcus was measured accurately by a digitiser, and the risk factors for coronary artery disease were examined according to the standard procedure used by the Lipid Research Clinics. The results show that the corneal arcus is more frequent in males; the frequency and size of corneal arcus are positively associated with age; there is a positive correlation between the size of corneal arcus and the levels of cholesterol and low-density lipoprotein in males; and that there is negative correlation between corneal arcus and diastolic blood pressure in both sexes. No associations were found between corneal arcus and other coronary artery disease risk factors such as triglyceride, high-density lipoprotein, very low-density lipoprotein, weight, Quetelet's ratio, glucose, and smoking.

Ocular signs and symptoms of altered blood lipids.

Several eye signs may present secondary to altered blood lipid levels. It is important to recognize these signs and their implications relative to both primary and secondary hyperlipoproteinemias. The significance of corneal arcus is age related, while isolated xanthelasma implies altered blood lipid levels in 30-50% of the cases. Eruptive xanthomas imply triglyceride levels in excess of 1500 mg% while lipemia retinalis presents when triglyceride levels exceed 2500 mg%. Retinal emboli present as a sign of an eroding atheroma and as such an indicator of the possibility of an impending stroke. Altered blood lipid levels represent a threat to life and must be recognized as early as possible to institute therapy. Therapy may be directed to either the primary or secondary causes of hyperlipoproteinemias.

Physical examination in ischaemic heart disease.

Physical examination can yield valuable diagnostic clues in a patient suspected of ischaemic heart disease. Examination during chest pain is especially informative. The haemodynamic abnormalities which accompany angina pectoris may precipitate elevation of blood pressure, pulsus alternans, pulsus bigeminus, abnormal precordial pulsations, a fourth heart sound or a systolic bruit; all of these may subsequently disappear with cessation of the anginal attack. Careful technique of examination, especially in detecting a fourth heart sound, is essential.