Paola Buscaglia

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.

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

Abstract 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.

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 χ2 (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 χ2 (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. J Cardiovasc Risk 5: 37-42

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.

Lipoprotein(a), Apolipoprotein(a) Polymorphism, and Insulin Treatment in Type II Diabetic Patients

et al. that this problem does not concern pumps in general. We also agree that the new adaptor for the H-Tron V-100, which is equipped with two small holes and can be closed with a red plug, should eliminate these problems as long as the pump is used according to the manufacturers specific instructions. We also fully support the recommendation suggested by Prendergast et al. to use the plug for the adaptor holes only when watertightness is needed (in the bath or shower) instead of removing it only when pressure problems are expected. When such instructions are followed, the H-Tron V-100 is at least an equal alternative to other pumps in the market.