[Can blood homocysteine explain the family history of vascular diseases?]. / Poderá a homocisteinemia explicar a história familiar da doença vascular?

INTRODUCTION AND AIMS: Family history of vascular disease is an important risk factor for vascular disease, independent of conventional risk factors. Homocysteinemia, a newly defined risk factor, is caused by genetics, such as cystathionine beta synthase deficiencies, and metabolic deficiencies. With the present work we intend to study the influence of family history of vascular disease in homocysteinemia. METHODS: We studied 204 normal persons (153 males), average age 38.7 +/- 10.9 years, in terms of family history of vascular disease (death due to myocardial infarction or a stroke), conventional risk factors, routine laboratory tests, fasting homocysteinemia and after oral methionine loading (0.1 g/Kg body weight). We compared laboratory results, conventional risk factors and homocysteinemia levels in persons with and without a family history of vascular disease. We performed covariance analysis to evaluate, in a multivariate model, factors that were related to basal or after methionine loading homocysteinemia. RESULTS: 35% of persons presented a family history of vascular disease (FHVD). Persons with FHVD presented higher age (45.6 +/- 8.9 versus 35.0 +/- 10.1, p < 0.001), and higher prevalence of hypertension (p = 0.002), dyslipidemia (p = 0.001), obesity (p = 0.03), and physical inactivity (p = 0.03). They presented a tendency, without statistical significance, to have a higher prevalence of diabetes and of hyperhomocysteinemia, and to present higher levels of basal and afterload homocysteinemia. Performing covariance analysis, basal homocysteinemia did not present any relation to FHVD. After methionine load homocysteinemia was strongly influenced by basal homocysteinemia (p = 0.0000), and significantly related to FHVD (p = 0.039). CONCLUSIONS: Homocysteinemia cannot explain most of the risk of family history of vascular disease, not explained by conventional risk factors. The only significant relationship between homocysteinemia and FHVD was observed with afterload homocysteinemia in the multivariate model. FHVD is clearly related to conventional risk factors.

[Prognosis significance of blood homocysteine after myocardial infarction]. / Significado prognóstico da homocisteinemia após enfarte do miocárdio.

INTRODUCTION AND AIMS: Homocysteinemia is an independent risk factor of coronary artery disease and of myocardial infarction. In the present study we intend to relate fasting homocystein levels to prognosis after a myocardial infarction. METHODS: From 1990 to 1992, we studied fasting homocysteinemia levels on a group of 112 patients aged under 56 years that had suffered a myocardial infarction between 3 and 12 months before. We obtained, the patients names, addresses, phone numbers and physicians' name. Seven years later (on average) we collected data regarding the patients evolution, consulting medical records, their physicians or by personal contact. We evaluated complications, namely mortality, vascular morbidity, such as unstable angina, re-infarction, stroke, and the need for invasive procedures (catheterism, PTCA, CABG). According to previous studies of the group, we used a cut-point of 10.10 mumol/L to define patients with normal or pathological levels of homocysteinemia. We excluded all patients that took vitamin B supplements, co-factors of HC metabolism, during this follow-up. RESULTS: We were able to obtain data on 110 patients. Patients with normal HC levels (n = 62) presented less global complications (26 versus 72%, p < 0.0001), non significant tendency to have lower mortality (1.6 versus 6%), had lower morbidity (14 versus 36%, p < 0.01) and lower invasive procedure need (18 versus 48%, p < 0.001). In the group with pathological homocystein levels (n = 48), those with higher homocystein levels presented a higher degree of complications. CONCLUSIONS: In this population with myocardial infarction under 56 years of age, a high homocysteinemia level is an important prognostic factor. This study suggests that we can improve the prognosis and decrease the complications after myocardial infarction by lowering elevated homocystein levels.

[Influence of smoking on homocysteinemia at baseline and after methionine load]. / Influência do tabagismo na homocisteinemia basal e após sobrecarga.

INTRODUCTION AND AIMS: Homocysteinemia (HC) and smoking are both important risk factors for vascular disease. In the present study, we intend to evaluate the influence of smoking habits on HC values as well as on vitamins B6, B12 and folic acid, co-factors of HC metabolism. METHODS: We measured fasting homocysteinemia (basal) and homocysteinemia 6 hours after an overload with 0.1 g methionine/kg body weight in 279 subjects. We also performed the dosage of plasma levels of B6 and B12 vitamins and of red cells folates. Smoking habits were inquired and the subjects were classified as non-smokers, current smokers or ex-smokers (if they had stopped smoking more than 1 month before the study). According to the smoking status, smokers were classified in three groups: less than 20 cigarettes a day, between 20 and 39 and 40 or more cigarettes a day. We studied basal and after methionine load homocysteinemia, B6, B12 and folic acid levels in each group. RESULTS: Smokers presented significantly higher levels of basal and after methionine load homocysteinemia then non-smokers (10.6 +/- 4.9 vs 9.4 +/- 2.6, and 26.8 +/- 10.0 vs 24.3 +/- 7.4 mumol/L, respectively, p < 0.05 for both and B6 levels (29.2 +/- 12.0 versus 32.6 +/- 12.0 mumol/L, p < 0.05). B12 and folic levels were similar in the two groups. These results were quite similar either in the normal subjects or in the subjects with a history of a cardiovascular event. The subjects who smoked 40 or more cigarettes per day, compared with those who smoked less then 20 cigarettes per day, presented higher levels of basal homocysteinemia (12.4 +/- 2.9 vs 10.0 +/- 5.5 mumol/L, p < 0.05) and lower levels of B6 (24.7 +/- 8.1 vs 31.7 +/- 12.6 mumol/L, p < 0.05). CONCLUSIONS: Smoking habits are related with the increase of basal and after methionine load homocysteinemia, probably because of a decrease in B6 vitamin levels. There is a proportional effect between the number of cigarettes smoked, B6 depletion and basal homocysteinemia increase. This study suggests that B6 vitamin supplements for smokers could decrease the vascular risk related with smoking habits.

[The effect of sex and menopause on basal blood levels of homocysteine and after methionine loading]. / Influência do sexo e da menopausa nos níveis de homocisteinemia basal e após sobrecarga com metionina.

INTRODUCTION AND OBJECTIVES: We have already proved that basal and after load homocysteinemia are risk factors for vascular disease and it is also known that premenopausal women are relatively protected against this disease. The objective of this paper was the assess whether there are any differences in the plasma levels of homocystein which might contribute to explain the differences in the incidence of vascular diseases found in both sexes. PATIENTS AND METHODS: Two hundred and four patients (153 males) without previous vascular disease were enrolled in the study. These patients were participating in a screening program for cardiovascular risk factors in a central hospital in Lisbon. We evaluated the basal homocysteinemia and homocysteinemia 6 hours after an oral load with methionine (0.1 g/kg body weight). Basal and after load homocysteinemia in men and women, as well as in women before and after menopause, was compared. Because homocysteinemia does not have a normal distribution, we used non-parametric statistical tests, namely the Mann-Whitney test. RESULTS: Men had higher values for basal homocysteinemia than women (mean and standard deviation)--9.64 +/- 3.15 versus 8.56 +/- 2.82 mumol/l, (p = 0.0018)--as well as for after load homocysteinemia--24.40 +/- 7.84 versus 23.71 +/- 10.16 mumol/L, non significant difference. Premenopausal women (n = 42) had lower basal homocysteinemia values than post menopausal women (n = 9)--8.41 +/- 3.02 versus 9.23 +/- 1.38 mumol/L, p < 0.05--and similarly after load homocysteinemia values--23.86 +/- 10.65 versus 23.01 +/- 7.47 mumol/L. CONCLUSIONS: Basal homocysteinemia is significantly higher in men than in women. After menopause, basal homocysteinemia levels increase significantly in women, approaching those in men. The levels of after load homocystein are not dependent on sex or pre- or postmenopausal condition. Homocysteinemia might explain, at least partly, the differences in the incidence of vascular disease in both sexes and the increased vascular risk in postmenopausal women.

[Homocysteinemia as a risk factor for cerebrovascular disorders. The role of age and homocysteine levels]. / A homocisteinemia como factor de risco de doença vascular cerebral. A importância da idade e dos nìveis de homocisteinemia.

PURPOSE: To evaluate importance of homocysteinemia as risk factor of thrombotic cerebrovascular disease, in terms of age and homocysteinemia levels. METHODS: A group of patients under 55 years old (n = 35, 21 males) that had suffered a stroke 3 months to 1 year before the study, defined by clinical criteria and the presence of cerebral infarction confirmed by tomography, without history or predisponents to embolic disease. The patients were matched with a group of controls without vascular pathology of a check-up program, in terms of age and sex. Patients and controls with history of alcoholism, signs or laboratory of renal or hepatic insufficiency or with history of recent ingestion of vitamins of the group B were excluded since these conditions could influence homocysteinemia levels. We measured to patients and controls the plasmatic basal homocysteinemia and homocysteinemia 6 hours after methionine overload of 0.1 g/Kg body weigh. We estimated case-control odds ratio of hyperhomocysteinemia globally and by age groups, and odd ratio of different levels of homocysteinemia. RESULTS AND CONCLUSIONS: Hyperhomocysteinemia case-control global odds ratio was 5.7, being higher in younger patients (8.8 below and 3.5 after the age of 45 years). Homocysteinemia as a risk factor of cerebrovascular disease presented as a continuous effect: low homocysteinemia was protective, and the higher the homocysteinemia, the higher the cerebrovascular risk proved to be. In these circumstances, heterozygozyty of cysthationine beta synthase deficiency, refered as the more important cause of hyperhomocysteinemia, cannot account for most of the cases of hyperhomocysteinemia.

Homocysteinaemia after methionine overload as a coronary artery disease risk factor: importance of age and homocysteine levels.

BACKGROUND: Homocysteinaemia is now accepted as an independent risk factor for coronary artery disease (CAD). Our goal was to study the influence of age plasma homocysteine level on the CAD risk attributable to homocysteinaemia. METHODS: We studied a group of 98 patients under 55 years of age who had suffered a myocardial infarction 3-12 months before the study. The patients were matched by sex and age with a group of 98 controls without vascular disease. We measured the plasma homocysteine levels 6h after a methionine overload of 0.1 g/kg body weight in patients and controls. Afterwards, the odds ratio for homocysteinaemia was determined by homocysteine level, and that for hyperhomocysteinaemia (homocysteine level > 34 mumol/l) by age group. RESULTS: After methionine loading, the homocysteine odds ratio varied from 0.47 (homocysteine level < 23 mumol/l) to 2.88 (homocysteine level > 34 mumol/l). In patients under the age of 46 the odds ratio for hyperhomocysteinaemia was 18.6. In patients between 46 and 55 years of age the odds ratio for hyperhomocysteinaemia was 1.2. CONCLUSIONS: Low homocysteine levels are protective against CAD, and the higher the homocysteine level the higher the coronary risk appears to be. This clearly means that heterozygosity for cystathionine beta synthase deficiency alone is not enough to explain the vascular risk associated with homocysteinaemia. Hyperhomocysteinemia was shown to be a significant risk factor only in patients under the age of 46 years old.

[Homocysteinemia as a risk factor in early cerebrovascular disease]. / A homocisteinemia como factor de risco de doença cerebrovascular precoce.

PURPOSE: To determine whether hyperhomocysteinemia represents a risk factor of early thrombotic cerebrovascular disease. METHOD: In a group of patients under 55 years of age (n = 33, 19 males) which had suffered a stroke from 3 months to 1 year before the study, defined by clinical criteria and presence of cerebral infarction confirmed by tomography, without history or predisposition to embolic disease. The patients were matched with a group of normal controls of checkup program, in terms of age, and sex. Patients and controls with a history of alcoholism, clinical or laboratory signs of renal or hepatic insufficiency or with a history of recent ingestion of Group B vitamins were excluded since these conditions would influence homocysteinemia levels. We measured the plasmatic basal homocysteinemia of patients and controls (HC) and 6 hours later a methionine overload of 0.1 g/Kg body weight (LOAD HC). RESULTS: Patients; Controls; Signific.; Age 46.0 +/- 7.7; 45.9 +/- 7.8; NS; Basal HC. 10.1 +/- 3.4; 8.5 +/- 1.7; p < 0.05; Load HC 28.0 +/- 7.6; 22.7 +/- 5.5; p < 0.01. CONCLUSION: In this study hyperhomocysteinemia appears as a risk factor for thrombotic cerebrovascular disease before the age of 55;-The measurement of homocysteinemia after the methionine loading test was more discriminative than the basal measurement;-A larger number of patients and controls will be necessary to establish the relative importance of homocysteinemia among other vascular risk factors in cerebrovascular disease.

[Homocysteinemia as a risk factor for early myocardial infarct--a case-control study]. / A homocisteinemia como factor de risco de enfarte do miocárdio precoce--estudo de casos e controlos.

PURPOSE: To investigate if hyper-homocysteinemia represents an independent risk factor of early coronary disease. METHODS: We studied a group of patients under 45 years old, that suffered a myocardial infarction from 3 months and 1 year before the study. The patients were matched with a group of normal controls of a check-up program, in terms of age, sex, smoking habits, presence of hypertension, obesity, (Quetelet Index), presence of diabetes, basal glycemia, total cholesterol, LDL and HDL cholesterol. Later we measured to patients (Pts) and controls (Cts) the plasmatic basal homocysteinemia (B HC) and 6 hours after a methionine overload of 0.1 g/kg body weight (L HC). RESULTS: [table: see text] CONCLUSIONS: In this study hyper-homocysteinemia appears as an independent risk factor of early coronary disease. The measurement of homocysteinemia after the methionine loading test was more discriminative than the basal measurement.