Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project.

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.

Baseline metabolic disturbances and the twenty-five years risk of incident cancer in a Mediterranean population.

BACKGROUND AND AIMS: Obesity is predictive of metabolic syndrome (metS), type 2 diabetes, cardiovascular (CV) disease and cancer. The aim of the study is to assess the risk of incident cancer connected to obesity and metS in a Mediterranean population characterized by a high prevalence of obesity. METHODS AND RESULTS: As many as 1133 subjects were enrolled in two phases and followed for 25 years (859 subjects) or 11 years (274 subjects) and incident cancer was registered in the follow-up period. Anthropometric measures and biochemical parameters were filed at baseline and evaluated as predictors of incident cancer by measuring hazards ratios (HR) using multivariate Cox parametric hazards models. Best predictive threshold for metabolic parameters and metS criteria were recalculated by ROC analysis. Fasting Blood Glucose >5.19 mmol/L [HR = 1.58 (1.0-2.4)] and the TG/HDL ratio (log10) (Males > 0.225, Females > 0.272) [HR = 2.44 (1.3-4.4)] resulted independent predictors of survival free of cancer with a clear additive effect together with age classes [45-65 years, HR = 2.47 (1.3-4.4), 65-75 years HR = 3.80 (2.0-7.1)] and male gender [HR = 2.07 (2.3-3.1)]. CONCLUSIONS: Metabolic disturbances are predictive of cancer in a 25 years follow-up of a Mediterranean population following a traditional Mediterranean diet. The high prevalence of obesity and metS and the observed underlying condition of insulin resistance expose this population to an increased risk of cardiovascular disease and cancer despite the healthy nutritional habits.

Hypertension and diabetes mellitus are associated with cardiovascular events in the elderly without cardiovascular disease. Results of a 15-year follow-up in a Mediterranean population.

BACKGROUND AND AIMS: Epidemiological prospective data on cardiovascular (CV) events in elderly subjects from Mediterranean populations are lacking. We aimed to investigate 15-year incidence of CV events and to evaluate the association with CV risk factors in an elderly Mediterranean population. METHODS AND RESULTS: The population of a small Sicilian village were enrolled, visited and a blood sample was drawn at baseline. CV events were recorded in the 15 years of follow-up. From 1351 subjects (75% of the resident population); 315 were in the age range 65-85 years; 266 subjects free from CV disease were analysed. Seventy-seven CV events were recorded in 73 out of 266 subjects, with a 19.7% rate (in 10 years). Hypertension (HTN) (hazards ratio=2.1) and diabetes mellitus (DM) (hazards ratio=1.8) were independently associated with CV events. Subjects with both DM and HTN showed a lower survival free of CV events compared to those with DM or HTN. CONCLUSIONS: In a 15-year follow-up of an elderly Mediterranean population free from CV disease, diabetes mellitus and hypertension were related to CV events. The control of risk factors in the elderly needs to be reinforced to achieve better results in terms of CV prevention.

The C(-260)>T gene polymorphism in the promoter of the CD14 monocyte receptor gene is not associated with acute myocardial infarction.

CD surface molecules mediates cell activation and signaling. In particular, CD14 on blood monocytes mediate monocyte/macrophage activation by lipopolysaccharide. Lipopolysaccharide and its receptor, CD14, have been implicated in atherogenesis. It has been recently shown that a C(-260)T polymorphism in the promoter of the CD14 receptor may be a risk factor for coronary artery disease. Recently this association has been questioned because no increased risk was found with the T allele, even in the homozygous state. In the present study we investigated a possible association between the C(-260)T polymorphism in the CD14 promoter and acute myocardial infarction. Two hundred and thrteen patients with and acute myocardial infarction 213 healthy controls were included in the study. Genotype frequencies of the C(-260)T polymorphism in the CD14 promoter were determined by polimerase chain reaction and the amplified product was cleaved with HaeIII. The frequency of the T allele was not significantly different in patients compared with controls. In this study we were not able to detect differences of frequency of the allele T (-260) in the promoter of the CD14 receptor gene in survivors of myocardial infarction and controls.

Two Italian kindreds carrying the Arg136-->Ser mutation of the Apo E gene: development of premature and severe atherosclerosis in the presence of epsilon 2 as second allele.

BACKGROUND AND AIMS: Type III hyperlipoproteinemia, or dysbetalipoproteinemia, is commonly associated with apolipoprotein E2 homozygosity (Cys112, Cys158). Apo E2-Christchurch (Arg136-->Ser), a rare mutation of the Apo E gene, located in the receptor-binding domain of the protein, has been found to be associated in the vast majority of cases of dysbetalipoproteinemia. METHODS AND RESULTS: This is the first report of two Italian kindreds carrying the Arg136-->Ser mutation. One family is a four-generation kindred from Genoa (Liguria, Italy) with a high rate of mortality due to coronary artery disease: the proband was a 51-year-old woman with previous myocardial infarction and residual angina, severe carotid atherosclerosis, peripheral arterial vascular disease and arterial hypertension. The other family was identified in Palermo (Sicily, Italy): the proband was an overweight 62-year-old man with a mixed form of hyperlipidemia. The mutation, which was identified by means of Apo E genotyping followed by direct sequencing, co-segregated with the same haplotype in the two families. CONCLUSIONS: The family histories and clinical examinations of these subjects clearly show that the Apo E Arg136-->Ser variant fully expresses a type III phenotype in association with a second allele coding for Apo E2, and only partially in association with a second allele coding for Apo E4.

Low-density-lipoprotein peak particle size in a Mediterranean population.

BACKGROUND: The predominance of small, dense low-density lipoprotein (LDL) particles ('LDL phenotype B') has been associated with a three-fold increased risk of myocardial infarction, but the feasibility of the identification of small, dense LDL as independent predictors of coronary artery disease risk in population studies remains questioned. Design We evaluated the LDL peak particle size and its relation with other established risk factors for coronary heart disease in a group of 156 randomized subjects living on the Mediterranean island of Ustica (71 males and 85 women, range of age 20-69 years), representing approximately 30% of the total population. RESULTS: The prevalence of LDL phenotype B subjects was low (approximately 15% in both men and women) and there was a clear trend for both genders in reducing the LDL peak particle size with age. Moreover, LDL phenotype B subjects had higher BMI values, prevalence of diabetes and plasma triglyceride (TG) levels and lower plasma HDL-C concentrations in comparison with LDL phenotype A individuals; in a multivariate analysis, plasma TG levels were the only variable independently associated with LDL peak particle size. CONCLUSIONS: In this population, which appears to be somewhat protected by premature coronary artery disease, a low prevalence of the LDL pattern B was found in both men and women, and plasma TG could have a key role in regulating the LDL peak particle size. The follow up, still ongoing, will provide useful information on the predictive role of LDL peak particle size on cardiovascular risk, at least in a low-risk population.

Autosomal recessive hypercholesterolemia in a Sicilian kindred harboring the 432insA mutation of the ARH gene.

We describe a Sicilian family presenting a recessive form of hypercholesterolemia harboring a mutation of the autosomal recessive hypercholesterolemia (ARH) gene. In two of the three sibs, a 26-year-old male and a 22-year-old female, a severe hypercholesterolemia was diagnosed with very high levels of plasma cholesterol (15.9 and 12.2 mmol/l, respectively); tendon xanthomatas and xanthelasms were present and in the male proband was documented a diffuse coronary atherosclerotic disease with a rapid and fatal progression. Both the parents had normal or slightly increased levels of plasma cholesterol. All causes of secondary hypercholesterolemia were ruled out as well as an involvement of the LDL receptor or apoB genes. Beta-Sitosterol plasma levels were in the normal range. Cultured fibroblasts from skin biopsy from parents and the two probands displayed a normal ability to bind and degrade 125I-LDL. Direct sequencing of ARH gene demonstrated the presence of a 432insA mutation in homozygosis in the two probands; parents were heterozygotes for the same mutation. This mutation is the first report of a mutation of the ARH gene responsible for recessive forms of hypercholesterolemia in Sicily.

Factor VII activity is an independent predictor of cardiovascular mortality in elderly women of a Sicilian population: results of an 11-year follow-up.

The aim of the Epidemiological project "Ventimiglia di Sicilia" is to identify the cardiovascular risk factors in a Sicilian population with a low risk profile and healthy nutritional habits. The risk of cardiovascular mortality in older subjects (over 60 years of age) is presented for an 11 year follow-up. Females showed higher prevalence of diabetes mellitus, hypertension, obesity and higher levels of total, LDL and HDL cholesterol, factor VII activity and fibrinogen compared to males. Cardiovascular mortality was related to hypertension and obesity in males, to high factor VII activity, obesity and diabetes mellitus in females. In a Logistic Regression model the same variables were independently correlated to cardiovascular mortality with the exception of obesity. In conclusion, these findings suggest that in a population with a low risk profile, other factors, such as factor VII activity, may emerge as predictors of cardiovascular mortality.

Distribution of risk factors, plasma lipids, lipoproteins and dyslipidemias in a small Mediterranean island: the Ustica Project.

BACKGROUND AND AIM: The populations of the Mediterranean area have a low incidence of cardiovascular disease (CHD). The aims of this paper are: 1) to present demographic data of the population of Ustica, a small island in the southern part of the Tyrrhenian sea that has reduced communications with the mainland and a diet presumably rich in fish; and 2) to evaluate the distribution of risk factors, plasma lipids, lipoproteins and dyslipidemias in this population. METHODS AND RESULTS: We invited all of the free-living resident population aged more than 14 years (about 800 individuals) to participate in the study; 576 responded, for a participation rate of about 73%. The distribution of cardiovascular risk factors, plasma lipids, lipoproteins and dyslipidemias were evaluated in all of the subjects. More than 60% of the population was out of the normal weight range. Total and low-density lipoprotein cholesterol levels were respectively 207.4 +/- 46.7 and 141.7 +/- 42.4 mg/dL, and similar in males and females. Lipoprotein (a) (Lp[a]) levels presented the classical "skewed" distribution and, among the apolipoprotein(a) isoforms, there was a clear predominance of intermediate-sized kringle IV repeats. Overall, 43% of the subjects had a lipid disorder: the prevalence of hypercholesterolemia was 22.8% (3.2% with severe hypercholesterolemia terolemia > or = 300 mg/dL); low high-density lipoprotein cholesterol levels were found in 22.5%; the so-called lipid triad in 2.1%; and high Lp(a) levels in 6.2%. Large familial clusters were found for some lipid disorders. CONCLUSIONS: A large prevalence of body weight disturbances and high frequency of dyslipidemias are the main characteristics of this population. Ongoing data and future longitudinal studies will better clarify the relative influence of each parameter on CHD risk and total mortality.

Carotid atherosclerosis in hypercholesterolemic patients: relationship with cardiovascular events.

BACKGROUND AND AIM: Extracranial cerebrovascular atherosclerosis is a common feature of hypercholesterolemia and carotid lesions are good predictors of cardiovascular events in the general population. Factors associated with the carotid damage of hypercholesterolemic patients and their relationships with the occurrence of clinical events are investigated in this study. METHODS AND RESULTS: One hundred and seventeen cardiovascular event-free hypercholesterolemic subjects underwent a complete clinical examination to look for additional risk factors. A blood sample was collected for lipoprotein determination and an ultrasound high resolution B-mode imaging examination of the common carotid arteries was performed. Patients were treated according to the current guidelines during a 4-yr follow-up and all major cardiovascular events were recorded. The prevalence of subjects with increased intima-media thickness and plaque was 21.4% and 29.9% respectively, higher than in normolipidemic controls. Carotid lesions were significantly related to age, hypertension and LDL-cholesterol and HDL-cholesterol levels. The relative risk of developing a major clinical event was 3.92 (95% CI 1.54-9.95, p < 0.004) among categories of carotid status. At multivariate analysis, cardiovascular events were independently related to the diagnosis of familial hypercolesterolemia (FH), baseline carotid score and mean levels of LDL-cholesterol and HDL-cholesterol during the follow-up. CONCLUSIONS: Common risk factors cooperate with plasma lipoprotein levels in increasing the frequency of carotid lesions of hypercholesterolemic patients. Since such lesions are useful predictors of clinical events, B-mode ultrasound evaluation of the carotids should be routinely included in the management of these patients.

Leukocyte count, diabetes mellitus and age are strong predictors of stroke in a rural population in southern Italy: an 8-year follow-up.

Stroke incidence rates in the Mediterranean area are higher compared to northern European countries. In this study, we present the 8-year prospective data from a small rural Sicilian town. This population, consisting of 1351 subjects (622 males and 729 females), is homogeneous for ethnic background with traditional healthy dietary habits and shows low cholesterol mean levels. We found that the risk of stroke was significantly associated with the record of at least one previous neurological symptom (PNS), such as lack of strength, loss of vision or speech or possible drop attacks, and high hematocrit in males, and to high body mass index (BMI) and waist-hip ratio (WHR), diabetes, hypertension, high leukocyte count in females. We also documented age-related differences: stroke was associated in younger subjects (age<65 years) with diabetes, high BMI, high uric acid levels and in older patients (age>/=65 years) with high WHR, hypertension, diabetes, PNS, leukocyte count and hematocrit above the 95th percentile. Multivariate analysis demonstrated an independent association between stroke and age, diabetes, leukocyte count, hypertension and PNS. In conclusion, in this rural Sicilian population, the incidence rate of stroke is 1.72 cases per 1000/year in the subjects between 40 and 75 years of age. The risk factors associated with stroke are different in younger and older subjects. Leukocyte count, as an expression of an undergoing inflammatory process, may have a relevant role at least in the elderly.

Prevalence of overweight and obesity in a rural southern Italy population and relationships with total and cardiovascular mortality: the Ventimiglia di Sicilia project.

OBJECTIVE: We investigated the prevalence of overweight and obesity and their relationships with the main cardiovascular risk factors in the population of Ventimiglia di Sicilia, a rural village in Southern Italy characterized by low cholesterol levels and by a low incidence of early coronary heart disease mortality. We related all deaths to body weight and fat distribution during an 8 y follow-up. DESIGN: Cross-sectional and prospective observational study. SUBJECTS: A total of 835 free-living individuals, 363 males and 472 females, of age between 20 and 69 y. MEASUREMENTS: In all participants body weight, waist-to-hip ratio (WHR), cardiovascular risk factors and plasma lipids were measured. During the follow-up, total and cardiovascular deaths were registered. RESULTS: We found a high overall prevalence of subjects with overweight or obesity (respectively 45.0% and 27.7%), with great differences among classes of age. As expected, body weight and fat distribution were associated with diabetes, hypertension, dyslipidemia and with a worsening of lipid profile. During the follow-up we registered 37 total and 11 cardiovascular deaths. All-cause and cardiovascular mortality risks were, respectively, 1.64 (95% CI 0.65-4.15) and 2.71 (95% CI 0.29-25.26) in subjects with a body mass index (BMI) of 27-29.99 kg/m2 and 2.45 (95% CI 1.03-5.87) and 5.36 (95% CI 1.41-62.01) in subjects with a BMI of > or =30 kg/m2 in comparison with participants with a BMI of <27 kg/m2, and 3.48 (95% CI 1.46-8.30) and 4.55 (95% CI 1.12-18.40) in subjects with a WHR higher than the median in comparison with individuals with a WHR lower than the median. CONCLUSION: The Ventimiglia di Sicilia Study highlights the great importance of overweight and obesity as a public health issue in a rural population and indicates that it is necessary to consider the impact of body weight and fat distribution on both total and CHD mortality.

[Characteristics of a statine of the most recent generation]. / Caratteristiche di una statina di ultima generazione.

LDL cholesterol levels are directly related to increased risk of cardiovascular disease. Several classes of drugs are available for the reduction of high cholesterol levels, but the highest efficacy has been demonstrated by HMG-CoA reductase inhibitors (statins). Cerivastatin is a third generation, synthetic statin, characterized by the highest pharmacological and therapeutic potency among currently marketed statins, and whose lipid-lowering efficacy has been demonstrated in a number of large, multicenter trials. Along with improvements in triglycerides and HDL cholesterol, cerivastatin at the dosage of 0.4 mg/day achieved a mean 36% reduction in LDL cholesterol. Analysis of clinical trials indicates that the molecule has age and gender-related effects, with a greater cholesterol reduction in women than in men and in elderly than younger patients. Cerivastatin has a dual hepatic metabolism pathway, via the CYP3A4 and CYP2C8 isoenzymes of cytochrome P450; therefore no potentially significant drug interactions with other CYP3A4 inhibitors, for instance erythromycin and itraconazole, have been reported. Cerivastatin tolerability profile at dosages investigated is similar to that of placebo.

Determinants of enhanced thromboxane biosynthesis in renal transplantation.

BACKGROUND: Despite great improvement in patient and graft survival, the long-term morbidity and mortality in renal transplant recipients (RTRs) are still significant, with a high incidence of cardiovascular disease-related deaths. METHODS: We investigated thromboxane (TXA2) biosynthesis and endothelial and coagulative activation in 65 patients who received a renal transplant. RESULTS: The rate of TXA2 biosynthesis (urinary 11-dehydro-TXB2 excretion largely reflects platelet TXA2 production in vivo) was significantly (P < 0.0001) higher in RTRs than in healthy subjects. Plasma von Willebrand factor (vWF) and thrombin-antithrombin (TAT) complexes were significantly higher (P < 0.001) in RTRs compared with controls. Urinary 11-dehydro-TXB2 directly correlated with plasma vWF and cholesterol. We next examined the relative influence of cyclosporine A (CsA) on TXA2 biosynthesis and endothelial activation, comparing a group of RTRs not receiving CsA with an age- and sex-matched group of patients treated with CsA. Urinary excretion of 11-dehydro-TXB2 and plasma levels of vWF were significantly increased in RTRs who received CsA compared with those who did not. After an overall follow-up of 120 months, RTRs who experienced cardiovascular events had a higher frequency of abnormal plasma levels of vWF than patients who remained event free. CONCLUSION: Renal transplantation is associated with in vivo platelet activation highly related to endothelial activation. This is particularly evident in CsA-treated patients. Administration of drugs that are able to reduce or eliminate thromboxane-dependent platelet activation in vivo may be beneficial to reduce the risk of cardiovascular events in RTRs.

Eating behaviour, body mass index and lipids of children in a free-living rural Sicilian population.

BACKGROUND AND AIM: The preliminary findings of an epidemiological study conducted in 1989 in Ventimiglia di Sicilia (a rural village in the hilly hinterland 50 km from Palermo) described a population mainly made up of farmers, which had a very low incidence of early cardiovascular mortality, lower total cholesterol plasma concentration than the Italian average, and nutritional habits following the criteria of the Southern Italian Mediterranean diet. Since a high prevalence of body weight abnormalities was found in this population and an 11-year follow-up revealed that both body weight and fat distribution were significantly associated with total and cardiovascular mortality, we studied the eating behaviour, body weight and lipid levels of 249 school-children living in the village. The aim of the study was to verify whether the children showed similar body weight abnormalities and quantitative dietary excesses as the adults of the same families. METHODS AND RESULTS: The dietary habits of 97 children (about one third of the study population) had a higher total caloric, monounsaturated fatty acid and fibre intake, and a lower saturated fatty acid and cholesterol intake, than an all-Italy sample of school-children. The lipid profile of this group of very young subjects was fairly good, but 13% had LDL-cholesterol levels of more than 130 mg/dL and 11% had HDL-cholesterol levels of less than 35 mg/dL. About 28% were considered to be above the 95th percentile of body weight and this was associated with a higher daily total caloric intake. CONCLUSIONS: Because obesity is associated with a high total caloric intake and various other risk factors even in young children, it is possible that a successful prevention campaign including behavioural education in schools could reduce the incidence of cardiovascular disease at older ages.

ApoE polymorphism in a small Mediterranean island: relationships with plasma lipids, lipoproteins and LDL particle size.

Polymorphisms of apoE gene are able to modulate lipoprotein metabolism at different steps and to influence LDL-cholesterol (LDL-C) levels and also other lipoproteins features. Population studies documented large differences in the frequency of apoE alleles which could be even related to the prevalence of cardiovascular disease. In this study we evaluated the apoE genotypes and allele frequency in 576 subjects living in a small island in the Tyrrhenian Sea and the relative contribution of apoE polymorphism on plasma lipid and lipoprotein profile, including LDL particle size. We found a cumulative frequency of 0.073, 0.866 and 0.061 for epsilon2, epsilon3 and epsilon4 alleles respectively. Moreover epsilon3 subjects had only triglyceride levels significantly lower and LDL-C and lipoprotein (a) (Lp(a)) levels higher than epsilon2 carriers. LDL-particle size was significant smaller in epsilon2 subjects than both epsilon3 and epsilon4 carriers, but the difference disappeared when data were adjusted for triglycerides. In conclusion we have provided further evidence of a low prevalence of epsilon4 allele in a Mediterranean population which may represent a genetic protective factor of these populations. Environmental factors, such as diet, occurring in this area may have attenuated the influence of this gene on plasma lipoproteins.

Italian familial defective apolipoprotein B patients share a unique haplotype with other Caucasian patients.

Familial defective apolipoprotein (apo) B-100 together with familial hypercholesterolemia are the two common genetic conditions that cause hypercholesterolemia. Familial defective apolipoprotein B-100 is due to mutations around codon 3500 of the apo B gene. The most-characterized mutation is a G>A transition at nucleotide 10,708 that results in the substitution of arginine by glutamine at codon 3500 (Apo B Arg3500Gln). Two other mutations are caused by a C>T transition, one at nucleotide 10,800 (Apo B Arg3531Cys) and the other at nucleotide 10,707 (apo B Arg3500Trp). In the present study we describe three new Italian cases of familial defective apolipoprotein B-100 (Apo B Arg3500Gln), one from the Liguria region and two from Sicily, and the haplotype of the apo B gene co-segregating with the mutation. By screening two groups of probands, clinically diagnosed as having Familial Hypercholesterolemia (700 from mainland Italy and 305 from Sicily), the prevalence of familial defective apolipoprotein B-100 due to Arg3500Gln was found to be very low (0.28% and 0.65%, respectively). The Arg3531Cys mutation was not detected in any proband. In the three new families with Arg3500Gln mutation in the present study and in one previously described in Italy, the mutation was associated with a unique apo B haplotype, which is consistent with data previously reported for Caucasian patients [XbaI-, MspI+, EcoRI-, presence of the 5' signal peptide insertion (Ins) allele, and the 49-repeat allele of the 3'-VNTR].

Effectiveness of screening for known mutations in Sicilian patients with "probable" familial hypercholesterolemia.

BACKGROUND AND AIM: More than 750 mutations in the low-density lipoprotein (LDL) receptor gene are currently known to cause familial hypercholesterolemia (FH), but the array of mutations varies considerably in different populations. The definition of essentially all the LDL receptor gene mutations in a population is therefore a prerequisite for the implementation of nation-wide genetic testing for FH. METHODS AND RESULTS: In this study, a screening strategy based on PCR-enzymatic digestion and PCR-allele specific hybridisation procedures was used to evaluate the frequency distributions of 11 known mutations in a cohort of 214 unrelated subjects meeting the diagnostic criteria of "probable" FH. We identified 20 mutation carriers (9.3%). One mutation (FH Palermo-1) occurred with a relatively high frequency, accounting for 7% of the entire study cohort. We also report the first observation of the receptor-negative mutation V408M (Afrikaner-2) in Italy. CONCLUSIONS: Our screening approach is not effective and, at least in our area, it is not a suitable alternative to the more expensive and time-consuming sequencing approach. However, our data suggest that it is possible to identify the molecular defect in about 10% of Sicilian patients with a clinical diagnosis of "probable FH" using a rapid laboratory diagnostic mutation panel. Four mutations were responsible for all of the diagnosed cases, and it could be reasonable to use this 4-mutation panel as a preliminary step before adopting a more complex laboratory approach.

Effects of Mediterranean diet on lipid levels and cardiovascular risk in renal transplant recipients.

BACKGROUND: Renal transplant recipients have an increased incidence of cardiovascular disease. These patients present abnormalities of lipoprotein profile which are persistent and involve an increasing number of individuals, suggesting the opportunity of an early therapeutic intervention. METHODS: We evaluated the effects of a 10- to 12-week diet based on the American Heart Association step-one diet criteria, modified with an increased intake of monounsaturated fats and alimentary fibers, on lipid profile and lipid-related cardiovascular risk in 78 normolipidemic and hyperlipidemic renal transplant recipients. RESULTS: Diet led to a significant reduction in total cholesterol levels by 10%, triglycerides by 6.5%, low-density lipoprotein (LDL)-cholesterol by 10.4% and LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol ratio by 10%, whereas HDL-cholesterol levels remained unchanged. Dividing renal transplant recipients into risk classes according to the National Cholesterol Expert Program guidelines and LDL-cholesterol levels, we observed a progressively increasing reduction in total cholesterol and LDL-cholesterol levels among 'desirable LDL-cholesterol', 'borderline high-risk LDL-cholesterol' and 'high-risk LDL-cholesterol' patients, while HDL-cholesterol levels did not change in any group and the LDL-cholesterol/HDL-cholesterol ratio significantly decreased in 'borderline high-risk LDL-cholesterol' and in 'high-risk LDL-cholesterol' patients (respectively by 6.8%, p < 0.05, and by 21.1%, p < 0.0001). Reduction in triglyceride levels was statistically significant only in subjects with 'desirable LDL-cholesterol' (by 12.3%, p < 0.01). Patients in the 'desirable LDL-cholesterol' class increased from 28 (35.9% of total patients) before diet to 45 (57.7% of total patients, p < 0.01), while subjects in the 'high-risk LDL-cholesterol' class reduced from 24 (30.8% of total patients) to 8 (10.2% of total patients, p < 0.005). CONCLUSION: These data suggest the possibility of a nutritional hypolipidemic approach in renal transplant recipients, even if normolipidemic. Dietetic treatment determined an inversion in the typical trend of renal transplant recipients, reducing instead of increasing the number of subjects with hypercholesterolemia, permitting the selection of individual candidates for further pharmacological treatment by carefully evaluating risk/benefit costs.

Lipoprotein(a) levels in relation to albumin concentration in childhood nephrotic syndrome.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a lipoprotein consisting of a low-density lipoprotein (LDL) particle linked to a polymorphic glycoprotein, apoprotein(a) [apo(a)]. Prior studies have reported high Lp(a) levels in the nephrotic syndrome, but it is still controversial whether this is due to the degree of hypoalbuminemia or proteinuria. METHODS: To investigate a model of nephrotic syndrome in the absence of renal failure, we studied a group of 84 children in different clinical stages of the disease for a period of five years. We evaluated the direct relationships between lipoproteins, including Lp(a), and/or plasma albumin and proteinuria. RESULTS: Lp(a) levels were significantly higher in the subjects with the active disease compared with patients in remission, and were also significantly different when subjects were ranked by albumin quartiles. Multiple regression analysis revealed that Lp(a) levels were inversely correlated with apo(a) isoform size and plasma albumin levels but not with the proteinuria/creatinine clearance ratio. Among subjects in complete remission, Lp(a) levels were different in patients with albumin levels below or above the fifth percentile. After the improvement of the clinical stage of the disease, the Delta% variation of albumin levels was related to the Delta% of apoB and LDL cholesterol (LDL-C), but not with the Delta% variation of Lp(a), whereas the Delta% variation of LDL-C was, in turn, related to the Delta% of Lp(a) levels. CONCLUSIONS: These results suggest that in the childhood nephrotic syndrome, the increased Lp(a) levels are mainly related to hypoalbuminemia, probably through a mechanism involving apoB overproduction, which leads to an increased number of LDL particles to be converted into Lp(a).