Large brachial artery diameter and diabetes in post-menopausal women.

BACKGROUND AND AIM: Vascular remodelling is one of the possible compensatory mechanisms in response to artery wall injury. It was demonstrated that post-menopausal women with carotid atherosclerosis had a larger brachial artery diameter (BAD) than women without carotid plaques. Therefore, it is possible to hypothesise that artery enlargement could be a marker of early atherosclerosis. To investigate the eventual association between carotid and brachial artery diameter and disease affecting the vascular wall, we performed a case-control study in post-menopausal women with or without type II diabetes mellitus. METHODS AND RESULTS: We enrolled 28 cases (with diabetes) and 56 controls (without diabetes) matched for age and carotid atherosclerosis presence and severity. On the t-test, women with diabetes showed significantly larger brachial and common carotid artery diameters and, as expected, higher plasma glucose level and homeostasis model assessment (HOMA) than women without diabetes. On the univariate analysis, only plasma glucose level results correlated to BAD in the whole sample. Multivariate analysis confirmed that diabetes was a good predictor of brachial and carotid artery diameter, while age, systolic blood pressure and triglycerides were correlated only to the carotid diameter. CONCLUSIONS: Our data confirm that vascular remodelling is a systemic process occurring in conditions related to atherosclerosis, such as type II diabetes. Indeed, artery diameter could be a marker of early response of vessel wall to injury.

Artery remodeling and abdominal adiposity in nonobese postmenopausal women.

BACKGROUND/OBJECTIVES: We aimed to assess, in nonobese postmenopausal women, whether markers of central adiposity, especially waist-to-hip ratio (WHR), would be associated with vascular remodeling. SUBJECT/METHODS: We enrolled 263 postmenopausal nonobese women without metabolic syndrome or diabetes. The strongest anthropometric measure related to brachial artery diameter (BAD) was WHR. Therefore, we divided the population in tertiles according to WHR values. Women in third tertiles were older, with higher body mass index, had worse lipid profile and a higher BAD than women in the first and second tertiles. RESULTS: An analysis of covariance confirmed that BAD was increased with increasing tertiles after correction for confounding variables. CONCLUSION: BAD, a surrogate measure of cardiovascular disease, was correlated to WHR in nonobese population; therefore, nonobese women with high WHR should be carefully considered because of a possible worse cardiovascular risk profile.

Lipoprotein(a), apolipoprotein(a) polymorphism and coronary atherosclerosis severity in type 2 diabetic patients.

BACKGROUND: Few and conflicting data are available in the literature on the association between Lp(a) levels and the severity of coronary artery disease (CAD) in diabetic patients. In addition, no studies took into account the role of apo(a) polymorphism. The purpose of the present study was to analyse the association of the degree of coronary atherosclerosis with Lp(a) levels and apo(a) polymorphism in a large group of type 2 diabetic patients. METHODS: The study population consisted of 227 consecutive type 2 diabetic patients undergoing a routine coronary angiography to evaluate chest pain or suspected CAD. The patients were subdivided into four subgroups according to the number of coronary arteries diseased: normal arteries (n=26), mono-vessel disease (n=67), bi-vessel disease (n=54) and multi-vessel disease (n=80). RESULTS: Lp(a) levels (normal arteries: 14.6+/-19.6 mg/dl; mono-vessel disease: 19.0+/-16.4 mg/dl; bi-vessel disease: 19.3+/-15.1 mg/dl; multi-vessel disease: 26.5+/-16.8 mg/dl; p<0.001) and the percentages of patients with at least one isoform of low molecular weight (normal arteries: 23.1%; mono-vessel disease: 38.8%; bi-vessel disease: 75.9%; multi-vessel disease: 81.2%; p<0.001) were significantly correlated with increasing number of coronary vessels diseased. Multiple logistic regression analysis showed that both Lp(a) levels (OR: 1.31; 95% CI: 1.02-4.11) and apo(a) polymorphism (OR: 3.43; 95% CI: 1.67-7.05) were independent predictors of CAD severity. CONCLUSIONS: Our data suggest that Lp(a) levels and apo(a) polymorphism may be reliable predictors of CAD severity in type 2 diabetic patients.

Erectile dysfunction and angiographic extent of coronary artery disease in type II diabetic patients.

Some studies observed an association between erectile dysfunction (ED) and coronary artery disease (CAD) extent in the general population, but others did not. There are no specific studies in diabetic populations. The aim of the present study was to evaluate whether ED is correlated with the extent of angiographic CAD in a large group of type II diabetic patients. We recruited 198 consecutive type II diabetic males undergoing an elective coronary angiography to evaluate chest pain or suspected CAD. Presence and degree of ED were assessed by the International Index Erectile Function - 5 (IIEF-5) questionnaire. ED was considered present, when IIEF-5 score was < or =21. Moreover, each domain of IIEF-5 was considered. Angiographic CAD extent was expressed both by the number of vessels diseased and by the Gensini scoring system. The percentage of subjects with ED was significantly higher (45.8 versus 15.8%; P=0.0120) in patients with (n=179) than in those without (n=19) significant angiographic CAD (stenosis of the lumen > or =50%). No significant association of CAD extent with presence of ED, total IIEF-5 score and each domain of IIEF-5 was observed. Our study shows that ED was significantly more prevalent in type II diabetic males with angiographic CAD than in those with normal arteries. However, no correlation was found between the extent of angiographic CAD and the presence or the severity of ED.

Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary artery disease in Type 2 diabetic patients and in non-diabetic subjects.

AIMS: We investigated whether in Type 2 diabetic patients lipoprotein(a) (Lp(a)) levels and apolipoprotein(a) (apo(a)) polymorphism are associated with angiographically documented coronary artery disease (CAD). We also examined whether there are differences in the distributions of Lp(a) levels and apo(a) phenotypes between CAD patients with and without diabetes. METHODS: A hundred and seven diabetic patients with CAD, 274 diabetic patients without CAD, 201 non-diabetic patients with CAD, and 358 controls were enrolled. RESULTS: Diabetic patients with CAD showed Lp(a) levels (21.2 +/- 17.7 vs. 15.1 +/- 17.8 mg/dl; P = 0.0018) and a percentage of subjects with at least one apo(a) isoform of low molecular weight (MW) (67.2% vs. 27.7%; P = 0.0000) significantly greater than diabetic patients without CAD. Multivariate analysis showed that in diabetic patients Lp(a) levels and apo(a) phenotypes were significantly associated with CAD; odds ratios (ORs) of high Lp(a) levels for CAD were 2.17 (1.28-3.66), while ORs of the presence of at least one apo(a) isoform of low MW were 5.35 (3.30-8.60). Lp(a) levels (30.2 +/- 23.7 vs. 21.2 +/- 17.7 mg/dl; P = 0.0005) and the percentage of subjects with at least one apo(a) isoform of low MW (87.0% vs. 67.2%; P = 0.0001) were significantly higher in CAD patients without than in those with diabetes. CONCLUSIONS: Our data suggest that Lp(a) levels and apo(a) phenotypes are independently associated with CAD in Type 2 diabetic patients; thus both these parameters may be helpful in selecting diabetic subjects at high genetic cardiovascular risk. However, Lp(a) levels and apo(a) polymorphism seem to be cardiovascular risk factors less important in diabetic than in non-diabetic subjects. Diabet. Med. 18, 589-594 (2001)

Severe hypercalcemia and systemic lupus erythematosus.

A rare case of severe hypercalcemia strongly associated with Systemic Lupus Erythematosus (SLE) is reported. On admission, a young woman showed severe hypercalcemia and photosensitivity. Criteria for diagnosis of SLE were not sufficient. All causes, common and uncommon, of hypercalcemia were excluded. Radiographs of the skeleton were normal. One year later diagnosis of SLE was evident. In addition, diffuse and severe osteopenia and chest deformities had occurred. The treatment of SLE normalized persistently calcemia. Mild elevation of calcium levels occurred during flares of SLE. It has been hypothesized that hypercalcemia in patients with SLE could be caused by the presence of stimulatory anti-PTH receptor antibodies. This case report suggests that in patients with severe hypercalcemia associated with SLE early diagnosis and treatment of SLE may prevent bone loss. In these patients the prevention of severe bone damage is very important. Indeed, severe osteopenia may favour skeletal deformities and fractures; in addition it may represent a serious obstacle in using adequate doses of glucocorticoids for treatment of SLE.

Genetics and cardiovascular risk: a role for apolipoprotein(a) polymorphism.

Apolipoprotein(a) [apo(a)] is the specific apolipoprotein of lipoprotein(a) [Lp(a)], a recognized cardiovascular risk factor. Apo(a) is characterized by a high genetic polymorphism with at least 34 isoforms in plasma. Recent studies have shown that in atherothrombosis apo(a) polymorphism could play a role independent of Lp(a) levels. In particular, apo(a) phenotypes seem to have their highest predictive value for coronary heart disease, when apo(a) isoforms are detected by high resolution phenotyping methods and when an adequate operative cut-off of apo(a) polymorphism is used. A strong association between apo(a) phenotypes and coronary heart disease has been also found in hypertensive, diabetic, and uremic patients. Moreover, apo(a) phenotypes seem to correlate well with the severity of coronary atherosclerosis and the age of clinical onset of coronary heart disease. These studies suggest that apo(a) polymorphism may have a great clinical usefulness in a primary prevention setting, since apo(a) phenotypes could be used together with Lp(a) levels as strong genetic predictors of atherothrombosis. The analysis of apo(a) polymorphism appears to be particularly useful in healthy subjects with a family history of atherothrombotic diseases, in patients with diseases at high cardiovascular risk (diabetes, hypertension, hypercholesterolemia) and in subjects with conditions modifying Lp(a) levels.

Association between apolipoprotein(a) phenotypes and coronary heart disease at a young age.

OBJECTIVES: The purpose of this study was to investigate lipoprotein(a) [Lp(a)] levels and apolipoprotein(a) [apo(a)] phenotypes in relation to age of onset of coronary heart disease (CHD). BACKGROUND: Although Lp(a) levels have been extensively analyzed in relation to age of CHD, apo(a) phenotypes have not. METHODS: Three hundred and thirty-five consecutive CHD patients were enrolled and grouped according to their age of CHD onset (<45 years; 45 to 54 years; > or = 55 years). RESULTS: In each patient group Lp(a) levels were higher than in an age-matched control group, but among the patient groups no differences in Lp(a) levels were observed. Apolipoprotein(a) phenotype distributions showed significant differences between patients and age-matched control subjects. Among the patient groups the difference in percentage of subjects with two apo(a) isoforms of low molecular weight (MW) was highly significant (p < 0.001). Multivariate analysis showed that apo(a) phenotypes were the best predictors of early CHD (p < 0.000001). The age-specific odds ratios (ORs) of the presence of at least one apo(a) isoform of low MW for CHD declined with age; in particular apo(a) phenotypes had their highest predictive value in younger persons (OR: 14.62). The OR for the presence of two isoforms of low MW/presence of only isoforms of high MW was 40.88 in the younger age group, 27.17 in age group of 45 to 54 years and 15.83 in the older age group. CONCLUSIONS: The present article reports the first evidence of a strong independent association of apo(a) phenotypes with the age of onset of CHD. Thus, if our data are confirmed by larger studies, apo(a) phenotypes might be used together with Lp(a) levels as powerful genetic markers in assessing the actual risk of developing CHD at a young age.

Apolipoprotein(a) phenotypes and their predictive value for coronary heart disease: identification of an operative cut-off of apolipoprotein(a) polymorphism.

BACKGROUND: Apolipoprotein(a) isoforms of low-molecular weight are associated with coronary heart disease. However, because of the high number of apolipoprotein(a) isoforms, it is difficult to assess the cardiovascular risk linked to the apolipoprotein(a) gene of a subject; indeed a cut-off of apolipoprotein(a) polymorphism has not been established. The aim of this investigation was to identify an 'operative' cut-off that discriminates apolipoprotein(a) isoforms associated with high genetic risk for coronary heart disease. METHODS: Two hundred and fifty-one patients with coronary heart disease and 284 controls were recruited. Apolipoprotein(a) isoforms were detected using a high-resolution phenotyping method. RESULTS: Twenty-seven apolipoprotein(a) isoforms with apparent molecular weight varying from 280 to 820 kDa were identified. Several cut-offs of apolipoprotein(a) polymorphism were used in order to compare the frequencies of apolipoprotein(a) isoforms of low and high molecular weight between patients and controls: the cut-off between 640 and 655 kDa had the highest chi 2 (130.40). Even when possible differences in apolipoprotein(a) phenotypes (subjects with at least one isoform of low molecular weight and subjects with only isoforms of high molecular weight) were assessed, the same cut-off showed the highest chi 2 (122.47). Multivariate analysis showed that apolipoprotein (a) isoforms had the greatest predictive value for coronary heart disease (F value = 107.0720), when the cut-off between 640 and 655 kDa was used. CONCLUSIONS: The cut-off between 640 and 655 kDa appears to be the most efficient in identifying subjects at high cardiovascular risk linked to apolipoprotein(a) gene, since this cut-off discriminates apolipoprotein(a) isoforms expressing a greater risk for coronary heart disease.

Apolipoprotein(a) phenotypes as genetic markers of coronary atherosclerosis severity.

We investigated Lp(a) levels and apo(a) polymorphism in relation to the severity of coronary artery disease, expressed both by the number of coronary arteries stenosed and three different coronary scoring systems. In a sample of 267 patients with coronary artery disease, a Mono-, Bi- or Multi-vessel coronary stenosis was documented by angiography. Twenty-five apo(a) isoforms were detected by a high resolution phenotyping method. Lp(a) levels did not show any differences among subgroups of patients. Both the percentage of apo(a) isoforms of low molecular weight (<655 kDa) (P=0.00015) and the percentage of subjects with at least one apo(a) isoform of low molecular weight (P=0.00027) were significantly correlated with increasing number of coronary vessels stenosed. In multivariate analysis, only apo(a) isoforms of low molecular weight were predictors of coronary atherosclerosis severity, when we used as the dependent variable both the '1-2-multi-vessels' categorization (P=0.000067) and the Gensini (P=0.008767), or Green Lane (P= 0.000001) or Dahlen (P=0.000102) coronary scoring system. Our data show that apo(a) isoforms of low molecular weight are associated with a greater severity of coronary atherosclerosis. If these data are confirmed by prospective studies, apo(a) phenotypes might be used as genetic markers of a greater severity of coronary atherosclerotic lesions.

Lipoprotein(a) levels and apolipoprotein(a) polymorphism in type 1 diabetes mellitus: relationships to microvascular and neurological complications.

To investigate plasma concentrations of lipoprotein(a) [Lp(a)] and apolipoprotein(a) [apo(a)] polymorphism in relation to the presence of microvascular and neurological complications in type 1 diabetes mellitus, 118 young diabetic patients and 127 age-matched controls were recruited. Lp(a) levels were higher in patients than in controls, but the apo(a) isoforms distribution did not differ between the two groups [higher prevalence of isoforms of high relative molecular mass (RMM) in both groups]. Microalbuminuric patients had Lp(a) levels significantly greater than normoalbuminuric patients, and normoalbuminuric patients showed higher Lp(a) levels than controls. Patients with retinopathy or neuropathy showed similar Lp(a) levels to those without retinopathy or neuropathy. No differences in apo(a) isoforms frequencies were observed between subgroups with and without complications (higher prevalence of isoforms of high RMM in every subgroup). However, among patients with retinopathy, those with proliferative retinopathy had higher Lp(a) levels and a different apo(a) isoforms distribution (higher prevalence of isoforms of low RMM) than those with non-proliferative and background retinopathy (higher prevalence of isoforms of high RMM). Our data suggest that young type 1 diabetic patients without microalbuminuria have Lp(a) levels higher than healthy subjects of the same age. Lp(a) levels are further increased in microalbuminuric patients. High Lp(a) levels and apo(a) isoforms of low RMM seem to be associated with the presence of proliferative retinopathy, but have no relation to neuropathy.

Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary heart disease in patients with essential hypertension.

BACKGROUND: Besides hypertension, several cardiovascular risk factors can play a role in the development of coronary heart disease (CHD) in hypertensive patients. Lipoprotein(a) [Lp(a)] is an important and independent cardiovascular risk factor, but its role in the development of CHD in hypertensives has not been studied. OBJECTIVE: To investigate whether or not Lp(a) levels and isoforms of apolipoprotein(a) [apo(a)] are predictors of CHD in patients with essential hypertension. METHODS: Lp(a) levels and apo(a) polymorphism were evaluated in 249 patients with essential hypertension, in 142 non-hypertensive patients with CHD and in 264 healthy controls. RESULTS: Hypertensives with CHD (n = 61) had Lp(a) levels [19 (range 0.5-73.5) versus 7 mg/dl (range 0-83.5), P < 0.001] and a percentage of apo(a) isoforms of low (< 655 kDa) relative molecular mass (RMM, 59.2 versus 25.9%, P < 0.001) higher than did those without CHD (n = 188). Moreover, there were more subjects with at least one apo(a) isoform of low RMM in the subgroup of patients with CHD than there were in that of those without CHD (80.3 versus 30.8%, P< 0.001). Lp(a) levels and apo(a) polymorphism did not differ significantly between hypertensive and non-hypertensive patients with CHD. Stepwise regression analysis indicated that high Lp(a) levels (P= 0.002073) and particularly the presence of at least one apo(a) isoform of low RMM (P < 0.000001) are strong predictors of CHD in hypertensive patients. CONCLUSIONS: Our data show that high Lp(a) levels and the presence of at least one apo(a) isoform of low RMM are strong and independent genetic risk factors for CHD in hypertensive patients. These findings suggest that Lp(a) and apo(a) isoforms should be assessed together with other cardiovascular risk factors to establish the overall CHD risk status of each hypertensive patient

Lipoprotein(a) plasma concentrations, apolipoprotein (a) polymorphism and family history of coronary heart disease in patients with essential hypertension.

AIM: The purpose of the study was to investigate lipoprotein (a) (Lp(a)) levels and apolipoprotein (a) (apo(a)) phenotypes, and their relationship with a family history of coronary heart disease (CHD) in patients with essential hypertension (EH). METHODS: One hundred and eight newly diagnosed patients with mild to moderate EH and 159 controls were studied. Lp(a) levels were determined with an ELISA method. Apo(a) isoforms were identified by a capillary immunoblotting technique. RESULTS: Lp(a) levels and frequency distribution of apo(a) isoforms did not show significant differences between patients and controls. Lp(a) levels in hypertensives with a family history of CHD were significantly higher than in those without a family history of CHD (P < 0.01). Hypertensives with a family history of CHD showed significantly different frequencies of apo(a) isoforms to those without a family history of CHD (P < 0.05). In EH patients with a family history of CHD, apo(a) isoforms of low molecular weight (MW) had a higher prevalence (62.6%), while in hypertensives without a family history of CHD, apo(a) isoforms of high MW were prevalent (81.6%); the difference between the two subgroups was significant (P < 0.001). Multivariate analysis showed that both Lp(a) levels and apo(a) isoforms of low MW are significant variables in distinguishing between the subgroups. CONCLUSIONS: Lp(a) levels and apo(a) phenotypes do not differ between hypertensives and controls. High Lp(a) levels and apo(a) isoforms of low MW are strongly associated with a family history of CHD in hypertensives. The quantification of Lp(a) levels and the characterization of apo(a) phenotypes may be used for assessment of familial predisposition to CHD in hypertensives.