Myocardial infarction in an adolescent: anomalous origin of the left main coronary artery from the right coronary sinus in association with combined prothrombotic defects.

We present the case of a 15-year-old boy with clinical features of an acute myocardial infarction. Angiography revealed a complete obstruction of the left main coronary artery. A coronary-aorto-bypass graft was undertaken immediately. Cardiac computed tomography demonstrated an anomalous origin of the left main coronary artery from the right coronary sinus of the aorta. A thrombophilic state with a heterozygote genotype for prothrombin G20210 mutation, a C677T methylenetetrahydrofolate reductase gene mutation, and a protein C type 1 deficiency was detected. No other embolic source could be identified. The patient recovered with persistent left ventricular dysfunction. He is now taking the anticoagulant warfarin. Combined prothrombotic defects in combination with additional risk factors such as coronary anomalies can lead to myocardial infarction even in children and adolescents.

Association of complement factor H Y402H gene polymorphism with different subtypes of exudative age-related macular degeneration.

OBJECTIVE: Exudative age-related macular degeneration (AMD) is a common cause for a severe central visual loss. The complement system has been implicated in the pathogenesis of drusen. Recently, a complement factor H (CFH) polymorphism, which is characterized by a tyrosine (Y)-to-histidine (H) exchange at position 402 of the CFH gene, has been suggested as a major risk factor for AMD in a North American population. The aim of the present study was to investigate a hypothesized association between the CFH Y402H polymorphism and the presence of exudative AMD in a Central European population of Caucasoid descent as well as to determine the genotype distribution among different types of exudative AMD. DESIGN: Retrospective case-control study. PARTICIPANTS: The study cohort consisted of 179 patients with exudative AMD and 163 controls. METHODS: Determination of genotypes was carried out by allele-specific digestion of polymerase chain reaction products. MAIN OUTCOME MEASURES: Genotypes of CFH Y402H polymorphism. RESULTS: The prevalence of the CFH 402HH genotype was significantly higher in patients with exudative AMD than among controls (35.2% vs. 8.6%; P<0.001). Homozygosity for the CFH Y402H polymorphism was associated with an odds ratio of 5.78 (95% confidence interval, 3.09-10.83) for exudative AMD. Subgroup analysis revealed that the CFH 402HH genotype was significantly more prevalent in eyes with predominantly classic with no occult choroidal neovascularization (CNV) than in those with either retinal angiomatous proliferation, occult with no classic CNV, or predominantly classic with occult CNV. CONCLUSION: Our data suggest that the CFH Y402H polymorphism is a major risk factor for exudative AMD in a Central European population.

Endoluminal therapy in patients with peripheral arterial disease: prospective assessment of quality of life in 190 patients.

OBJECTIVE: The objective of our study was to assess the impact of endoluminal treatment on health-related quality of life in patients with peripheral arterial disease. SUBJECTS AND METHODS: Changes in quality of life were prospectively evaluated in 190 patients before and 1, 3, 6, and 12 months after treatment. Physical, emotional, and general health components were determined using the short-form (36 items) health survey (SF-36). Claudicant patients were compared with patients who had critical limb ischemia. The influence of the lesion location (iliac, femoropopliteal, or crural) restenosis, and additional interventions on quality of life were evaluated. RESULTS: Six- and 12-month follow-up data were available for 136 and 103 patients, respectively. Significant improvements in quality of life were observed in most of the patients after the intervention. Many of the SF-36 scores decreased from the 6- to the 12-month follow-up but remained significantly higher than the score before the intervention. Reduction of bodily pain was the most evident effect of treatment. Claudicant patients seemed to benefit more from treatment than patients with critical limb ischemia. In terms of SF-36 scores, percutaneous transluminal angioplasty of the crural arteries was equally as effective as endoluminal revascularization of the iliac and femoropopliteal arteries and multilevel interventions were as effective as single-level interventions. The occurrence of a restenosis was significantly related to lower SF-36 scores, and restenosis not followed by a second intervention was associated with lower SF-36 scores. CONCLUSION: Although there were several differences between the groups, significant improvements in quality of life up to 12 months after endoluminal therapy were observed in most patients.

Angiotensin-converting enzyme insertion/deletion polymorphism and retinal artery occlusion.

PURPOSE: An insertion/deletion (I/D) polymorphism of the gene for angiotensin-converting enzyme (ACE) is associated with higher ACE plasma levels and activity. This enzyme is known to play an important role in blood pressure regulation and the ACE I/D gene polymorphism has been suggested as a risk factor for atherosclerotic vascular diseases. The purpose of the present study was to investigate a hypothesized association between the ACE I/D polymorphism and retinal artery occlusion (RAO). METHODS: A total of 159 patients with RAO and 304 control subjects were enrolled in the present retrospective case-control study. ACE I/D genotypes were determined by polymerase chain reaction. RESULTS: Allelic frequencies and genotype distribution of the ACE I/D polymorphism did not significantly differ between patients and control subjects (ACE DD 25.8% versus 28.0%; p = 0.36). A logistic regression analysis predicted the presence of RAO by arterial hypertension and current smoking status, but not by ACE I/D genotypes. CONCLUSION: Our data suggest that the ACE I/D polymorphism is not a major risk factor for RAO.

Methylenetetrahydrofolatereductase (MTHFR) 677C>T polymorphism and open angle glaucoma.

PURPOSE: Increased plasma homocysteine levels have been found in patients with primary open angle glaucoma (POAG) and glaucoma secondary to pseudoexfoliation syndrome (PEXG). A common polymorphism of the methylenetetrahydrofolatereductase (MTHFR 677C>T) leads to moderately elevated plasma homocysteine levels particularly under conditions of impaired folate status. It was the aim of this study to investigate a hypothesized association between this polymorphism and the presence of either POAG or PEXG. METHODS: The present retrospective case-control study included a total of 553 participants comprising 204 patients with POAG, 138 patients with PEXG, and 211 control subjects. Genotyping for the MTHFR 677C>T polymorphism was performed by polymerase chain reaction (PCR). RESULTS: No significant difference in the genotype distribution of the MTHFR 677C>T polymorphism was found between control subjects and patients with POAG or PEXG. The prevalence of the MTHFR 677TT genotype was 6.9% in patients with POAG, 11.6% in patients with PEXG, and 9.5% in control subjects. CONCLUSIONS: The present data suggest that the MTHFR 677C>T polymorphism itself is not a major genetic risk factor for POAG and PEXG in a central European population.

Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy.

Mild hyperhomocysteinemia is established as an independent risk factor for atherothrombotic disease, including ocular pathologies such as retinal vascular occlusion and non-arteritic ischemic optic neuropathy (NAION). Low intake or low status of B-vitamins explains elevated total homocysteine (tHcy) concentrations only in part. The underlying cause for disturbed homocysteine metabolism requires further insight. We investigated whether the combined determinations of plasma tHcy, methylmalonic acid (MMA) and cystathionine provide more information on the causes of impaired homocysteine metabolism as compared with vitamin B12, vitamin B6 and folate in patients with ocular ischemic vascular disease. A total of 51 hyperhomocysteinemic (>12 micromol/L) patients with retinal vascular occlusion (n=42) and NAION (n=9) were included. Mild renal dysfunction was an important determinant of tHcy, indicated by the positive correlation between creatinine and tHcy (r=0.47, p=0.001). The assessment of MMA in addition to tHcy identified at least 12 out of 51 patients (23%) who were most likely to have a functional vitamin B12 deficiency. An additional 14 patients (27%) with elevated MMA and cystathionine levels also had slightly elevated concentrations of creatinine, pointing to the need for discrimination between renal dysfunction and vitamin B12 deficiency in this group. In contrast, measurement of cystathionine is very sensitive for renal dysfunction and this marker was strongly related to serum creatinine (r=0.56, p<0.001) and to tHcy (r=0.50, p<0.001). Measurement of the vitamins folate, vitamin B12 and vitamin B6 in plasma did not provide sufficient information on intracellular disturbances in homocysteine metabolism. In conclusion, the metabolites homocysteine, cystathionine and MMA are sensitive indicators and valuable for discrimination of the underlying cause of mild to moderate hyperhomocysteinemia, with implications for therapeutic targeting.

Role of thrombophilic gene polymorphisms in branch retinal vein occlusion.

OBJECTIVE: Branch retinal vein occlusion (BRVO) is a common cause of severe visual loss. Numerous risk factors, including arterial hypertension, diabetes mellitus, and arteriosclerosis, have been identified. Gene polymorphisms affecting hemostasis may also play a role in the pathogenesis of BRVO. The present study was therefore done to determine the prevalence of genetic polymorphisms in factors implicated in hypercoagulability among patients with BRVO. DESIGN: Retrospective case-control study. PARTICIPANTS: The study cohort consisted of 294 patients with BRVO and 294 control subjects, matched for age and gender. METHODS: Determination of genotypes was done by allele-specific digestion of polymerase chain reaction products, or by 5' exonuclease assay (TaqMan). MAIN OUTCOME PARAMETERS: Genotypes of factor V R506Q (factor V Leiden), prothrombin 20210G>A, fibrinogen beta -455G> A, factor XII (FXII) 46C>T, and ITGA2 807C>T (platelet glycoprotein Ia [GPIa] 807C>T) and ITGB3 L59P (platelet GPIIIa PlA1/PlA2) polymorphisms. RESULTS: Genotype distributions of the investigated gene polymorphisms did not differ significantly between patients and control subjects. In contrast, significantly increased prevalences of arterial hypertension and hypercholesterolemia were found among patients with BRVO. In a logistic regression analysis, the presence of arterial hypertension was associated with an odds ratio (OR) of 2.32 (95% confidence interval [CI], 1.62-3.32), whereas hypercholesterolemia yielded an OR of 2.54 (95% CI, 1.74-3.70) for BRVO. CONCLUSION: Our data indicate that the prevalences of the investigated gene polymorphisms do not differ significantly in patients with BRVO and control subjects. This suggests that these polymorphisms are not major risk factors for BRVO.

Hyperhomocyst(e)inemia, but not methylenetetrahydrofolate reductase C677T mutation, as a risk factor in branch retinal vein occlusion.

OBJECTIVE: To determine whether hyperhomocyst(e)inemia and methylenetetrahydrofolate reductase (MTHFR) C677T mutation are associated with branch retinal vein occlusion (BRVO). DESIGN: Retrospective, case-control study. PARTICIPANTS: The study cohort consisted of 84 consecutive patients with branch retinal vein occlusion and 84 controls, matched for age and gender. MAIN OUTCOME MEASURES: Fasting plasma homocyst(e)ine, folate, and vitamin B(12) levels, MTHFR C677T genotypes. RESULTS: Mean plasma homocyst(e)ine levels were significantly higher in patients than in controls (11.4 +/- 4.3 micromol/l vs. 9.9 +/- 2.8 micromol/l; P = 0.002). An increase of plasma homocyst(e)ine level by 1 micromol/l was associated with an odds ratio of 1.19 (95% confidence interval 1.06-1.34; P = 0.004). Mean plasma folate levels were significantly lower in patients than in the control group (4.5 +/- 2.1 ng/ml vs. 5.6 +/- 2.1 ng/ml; P = 0.007). The prevalence of the homozygous genotype of the MTHFR C677T mutation did not differ significantly between patients and controls. CONCLUSIONS: Our results suggest that hyperhomocyst(e)inemia, but not homozygosity for the MTHFR C677T mutation, is associated with BRVO. Increased plasma homocyst(e)ine levels in our study are not the result of an increased prevalence of the homozygous genotype of MTHFR C677T mutation.

Hyperhomocyst(e)inemia and MTHFR C677T genotypes in patients with central retinal vein occlusion.

BACKGROUND: Elevated plasma homocyst(e)ine is a major risk factor for venous thrombosis and cardiovascular disease. Homozygosity for the MTHFR C677T mutation and low plasma folate levels increase plasma homocyst(e)ine concentrations. The aim of this retrospective case-control study was to investigate a possible association between hyperhomocyst(e)inemia and central retinal vein occlusion. METHODS: Our study included 78 consecutive patients with central retinal vein occlusion and 78 control subjects, matched for age and sex. High-performance liquid chromatography (HPLC) with fluorescence detection was used to determine fasting plasma homocyst(e)ine concentrations. Plasma folate and vitamin B12 levels were determined by immunological assays. Genotyping for the MTHFR C677T mutation was performed by polymerase chain reaction (PCR). RESULTS: Hyperhomocyst(e)inemia was defined by the 95th percentile of plasma homocyst(e)ine concentrations in the control group (=14.83 micromol/l). Thus 16 patients with central retinal vein occlusion were diagnosed as hyperhomocyst(e)inemic, compared with three control subjects ( P=0.001). The odds ratio of hyperhomocyst(e)inemia for central retinal vein occlusion was 5.29 (95% CI 1.33-21.13). Mean plasma folate levels were significantly lower in patients than in controls (3.94+/-1.94 ng/ml vs. 5.69+/-2.09 ng/ml; P<0.001). Distribution of MTHFR C677T genotypes did not significantly differ between the two groups. CONCLUSIONS: Our study suggests that hyperhomocyst(e)inemia, but not the MTHFR C677T mutation, is associated with central retinal vein occlusion.

Chlamydia pneumoniae seropositivity and the risk of nonarteritic ischemic optic neuropathy.

OBJECTIVE: To determine whether IgG antibodies to Chlamydia pneumoniae are associated with nonarteritic ischemic optic neuropathy (NAION). DESIGN: Retrospective case-control study. PARTICIPANTS: The study cohort consisted of 71 consecutive patients with NAION and 71 controls matched for age and gender. MAIN OUTCOME MEASURES: Serum immunoglobulin G (IgG) antibody titers to Chlamydia pneumoniae. RESULTS: Patients with NAION had significantly higher IgG antibody titers to C. pneumoniae compared with control subjects (IgG titer > or =1:128: 29 patients versus 15 controls, P = 0.017). The odds ratio for patients with an IgG titer > or =1:128 was 2.56 (95% confidence interval [CI], 1.2-5.5). Adjustment for arterial hypertension, diabetes mellitus, and myocardial infarction resulted in an odds ratio of 3.48 (95% CI, 1.3-9.6). CONCLUSIONS: Our results suggest that elevated titers of IgG antibodies to C. pneumoniae are associated with NAION.