Can LDL cholesterol be too low? Possible risks of extremely low levels.

Following the continuous accumulation of evidence supporting the beneficial role of reducing low-density lipoprotein cholesterol (LDL-C) levels in the treatment and prevention of atherosclerotic cardiovascular disease and its complications, therapeutic possibilities now exist to lower LDL-C to very low levels, similar to or even lower than those seen in newborns and nonhuman species. In addition to the important task of evaluating potential side effects of such treatments, the question arises whether extremely low LDL-C levels per se may provoke adverse effects in humans. In this review, we summarize information from studies of human cellular and organ physiology, phenotypic characterization of rare genetic diseases of lipid metabolism, and experience from clinical trials. Specifically, we emphasize the importance of the robustness of the regulatory systems that maintain balanced fluxes and levels of cholesterol at both cellular and organismal levels. Even at extremely low LDL-C levels, critical capacities of steroid hormone and bile acid production are preserved, and the presence of a cholesterol blood-brain barrier protects cells in the central nervous system. Apparent relationships sometimes reported between less pronounced low LDL-C levels and disease states such as cancer, depression, infectious disease and others can generally be explained as secondary phenomena. Drug-related side effects including an increased propensity for development of type 2 diabetes occur during statin treatment, whilst further evaluation of more potent LDL-lowering treatments such as PCSK9 inhibitors is needed. Experience from the recently reported and ongoing large event-driven trials are of great interest, and further evaluation including careful analysis of cognitive functions will be important.

Functional foods and cardiometabolic diseases* International Task Force for Prevention of Cardiometabolic Diseases.

Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its very beginning, and additional research is necessary to substantiate the potential health benefit of foods for which the diet-health relationships are not yet scientifically validated. It appears essential, however, that before health claims are made for particular foods, in vivo randomized, double-blind, placebo controlled trials of clinical end-points are necessary to establish clinical efficacy. Since there is need for research work aimed at devising personalized diet based on genetic make-up, it seems more than reasonable the latter be modeled, at present, on the Mediterranean diet, given the large body of evidence of its healthful effects. The Mediterranean diet is a nutritional model whose origins go back to the traditional dietadopted in European countries bordering the Mediterranean sea, namely central and southern Italy, Greece and Spain; these populations have a lower incidence of cardiovascular diseases than the North American ones, whose diet is characterized by high intake of animal fat. The meeting in Naples and this document both aim to focus on the changes in time in these two different models of dietary habits and their fall out on public health.

Which is the eligible patient to be treated with pioglitazone? The expert view.

Pioglitazone has an important role in the treatment of patients with Type 2 diabetes. The drug can help patients to achieve sustained glycemic control and may delay the requirement for insulin. Pioglitazone may provide benefits beyond its effects on glycemia, with data suggesting it may confer anti-atherosclerotic and cardioprotective properties. Attention should be given to possible side effects relating to class effects of TZD, and selection of appropriate patients to be prescribed pioglitazone will enable optimum benefits to be derived from pioglitazone treatment.

[What are the causes and the reason why of diseases prevalence and incidence in occupational sample of women]. / Prevalenza ed incidenza di malattie nelle donne che lavorano: quali e perché.

UNLABELLED: Aim of this study has been the evaluation of health status change among women and men engaged in different occupational activities. METHODS: In a sample of 1,145 women and 3,110, collected in a time span of 10 years, were calculated prevalence and incidence of diseases related to occupational and non occupational variables: physical work load and job timing, civil status and family engagement. Differences between sexes were calculated by X-square and mean difference test. RESULTS: In women subset, cardiovascular and vertebral degenerative disease, skin, wrist and elbow (carpal canal and epicondylitis) pathologies were much more represented than in men's ones. Psychiatric and psychosomatic symptoms and diseases were much more represented in the women sample and furthermore at younger age. In women, heavier work load has been the most responsible factor of degenerative diseases, while shift work of psychiatric and psychosomatic diseases. In the same gender, the stable living together and family charge increased the incidence of chronic degenerative diseases, suggesting an empowering effect coming from the occupation. In conclusion, from data analysis it is possible to speculate that working women's health profile is sensible to various determinants with synergic effect; consequently the clinical emergence of diseases is shown up earlier.

Drinking habits and health in Northern Italian and American men.

BACKGROUND AND AIM: The aim of this study was to investigate alcohol drinking habits in two male cohorts, one Italian and one American, and to investigate whether cardiovascular disease risk factors are related to different drinking patterns. Furthermore, socio-demographic characteristics were taken into account. METHODS: The Italian sample was drawn from the National Alpines Association. A dietary questionnaire was sent to the members of this association as an additional supplement to their monthly magazine. Eleven thousand one hundred and thirty-four men, 18-94 years, from Northern Italy were included in this analysis. The American sample is part of the Western New York Health Study (WNYHS) including 1927 male participants. RESULTS: In both populations, those who drank more than 4 drinks/day were the least educated and showed the highest percentage of current smokers; the highest prevalence of hypertension occurred in heavier drinkers and those who mostly drank without food. By contrast, lifetime abstainers exhibited the lowest percentage of hypertension and the highest level of serum cholesterol; in both populations the highest prevalence of diabetes was present in lighter drinkers. CONCLUSIONS: The current study shows that drinking habits are quite different in the two countries and are basically linked with socio-demographic and behavioral variables and support the notion that excess volume of alcohol consumed, and drinking without food, are associated with a higher risk of hypertension and hyperlipidaemia, particularly for Italians.

Effects of working posture and exposure to traffic pollutants on sperm quality.

An increasing difficulty of couples in achieving pregnancy related to male infertility has been reported. Several factors have been implicated as possible causes of this decrease, including the exposure to the endocrine disruptors and the environmental toxicants, the changes in lifestyle and the exposure to heat. The aim of this study was to evaluate the role of working posture when associated to nitrogen oxides exposure. Three hundred and seven male workers, employed in a motorway company, were enrolled into the study, underwent a complete physical examination and laboratory evaluations, endocrine screening and sperm analysis. Taking into account the exposure to fuel combustion gases and the working posture, sitting or free, the study population was divided in 4 groups. In the subjects occupationally exposed to NO2, a significant lower sperm total motility was observed than in not exposed workers. In the workers with obliged sitting working posture, lower sperm motility was also observed than in the workers with free working posture. Differences in sperm quality were strong when chemical and postural risk factors were associated. The findings of this study confirmed detrimental effects of nitrogen dioxide as a marker of traffic pollutants, showing alterations of sperm quality even if the environmental concentration of gas is very low according to the limits established by the Italian legislation. They suggest, also, the possible interaction between chemical exposure and obliged sitting position.

High-circulating leptin levels are associated with greater risk of hypertension in men independently of body mass and insulin resistance: results of an eight-year follow-up study.

BACKGROUND: We previously reported a significant association between plasma leptin (LPT) concentration and blood pressure (BP), which was partly independent of serum insulin levels and insulin resistance. The aims of this study were to detect whether serum LPT levels predict the development of hypertension (HPT) in the 8-yr follow-up investigation of a sample of an adult male population (the Olivetti Heart Study), and to evaluate the role of body mass index (BMI) and insulin resistance in this putative association. PATIENTS AND METHODS: The study population was made up of 489 untreated normotensive subjects examined in 1994-1995 (age: 50.1 +/- 6.7 yr; BMI: 26.3 +/- 2.8 kg/m(2); BP: 120 +/- 10/78 +/- 6 mm Hg; and homeostatic model assessment index: 2.1 +/- 1.6). RESULTS: The HPT incidence over 8 yr was 35%. The participants with incident HPT had similar age but higher BMI (P < 0.001), serum LPT (P < 0.001), and BP (P < 0.01) at baseline. One sd positive difference in baseline serum LPT log was associated at univariate analysis with a 49% higher rate of HPT [95% confidence interval (CI) 22-83; P < 0.001]). In three different models of multivariable logistical regression analysis, LPT was respectively associated with a 41% greater risk to develop HPT (95% CI 15-74; P < 0.001) upon adjustment for age and baseline BP, with a 48% (95% CI 20-81) greater risk when adding the homeostatic assessment model index to the model, and with 33% greater risk (95% CI 6-67; P < 0.02) upon adjustment for BMI. CONCLUSIONS: In this sample of originally normotensive men, circulating LPT level was a significant predictor of the risk to develop HPT over 8 yr, independently of BMI and insulin resistance.

Increased prevalence of celiac disease without gastrointestinal symptoms in adults MICA 5.1 homozygous subjects from the Campania area.

OBJECTIVES: Polymorphisms in the major histocompatibility complex class I chain-related gene A may influence its binding to the Natural Killer Cell Receptor G2D (NKG2D). We looked for polymorphisms in major histocompatibility complex class I chain-related gene A exon 5 and in Human Leukocyte Antigen (HLA)-DQ/DR in adult coeliac disease patients to determine whether they affected coeliac disease phenotypes. METHODS: Adult coeliac disease patients with (n=98) and without (n=93) gastrointestinal symptoms (gastrointestinal symptoms+/gastrointestinal symptoms-) and 108 control subjects from Campania (Italy) were characterized by Polymerase Chain Reaction (PCR) sequence specific oligonucleotide followed by PCR sequence specific primer assays for HLA DQ/DR, and by PCR followed by capillary electrophoresis for major histocompatibility complex class I chain-related gene A exon 5 polymorphisms. Immunoglobulin A (IgA) anti-transglutaminase antibodies were also evaluated by immunosorbent assay. RESULTS: Five different major histocompatibility complex class I chain-related gene A alleles were detected in both coeliac disease patients and control subjects. The major histocompatibility complex class I chain-related gene A 5.1 allele occurred more frequently in patients than in controls (p<0.05), and the major histocompatibility complex class I chain-related gene A 5.1/5.1 homozygous genotype increased the risk of gastrointestinal symptoms- coeliac disease (OR=2.79, 95% CI 1.15-6.79). Gastrointestinal symptoms- coeliac disease patients bearing major histocompatibility complex class I chain-related gene A 5.1/5.1 alleles showed lower anti-transglutaminase levels (18U/L) than the gastrointestinal symptoms+ coeliac disease patients (35U/L). HLA-DQ2/DQ8 genotypes did not differ between gastrointestinal symptoms+ and gastrointestinal symptoms- coeliac disease, although DQ8 tended to be more frequent in gastrointestinal symptoms- coeliac disease (11.7%) than in gastrointestinal symptoms+ coeliac disease (6%). CONCLUSIONS: Our study shows that a double dose of the major histocompatibility complex class I chain-related gene A 5.1 allele could predispose to the onset of gastrointestinal symptoms- coeliac disease. We can hypothesize that a lower level of immunological involvement in gastrointestinal symptoms- coeliac disease patients is associated with absence of gastrointestinal symptoms. This test could represent a second step in the genetic typing of high-risk subjects such as first-degree relatives of coeliac disease patients positive for the DQ2/DQ8 molecule.

[Importance of physical activity for prevention of chronic diseases]. / L'importanza dell'attività fisica nella prevenzione delle malattie cronico degenerative.

A lot of epidemiological studies have shown that physical activity can prevent the development of chronic diseases such as obesity, diabetes, osteoporosis, cardiovascular diseases and cancer Physical activity can be classified by rate of energy expenditure: light intensity 1-3 METs, moderate 3-6 MET's, vigorous 6-9 MET's, very vigorous >9 MET's. Although it is evident that an active lifestyle has many health benefits and sedentary habits are associated with an increased risk of chronic diseases, the debate still continues as to how much, what type, how often, at what intensity physical activity should be performed to have a positive effect on the health. Reduction of cardiovascular risk is observed already with a moderate intensity physical activity (3-6METs); whilst to improve physical fitness training must be more vigorous (6-9 METs). In conclusion good goals are achieved when moderate levels of physical activity are performed on a regular basis (at least 3- 5 days a week for 30 minutes). But to reach also countable results on body weight control the frequency should be 5-7 days a week for 60 minutes.

[Smoking habit among workers in Campania region]. / L'abitudine al fumo nei lavoratori Campani.

Smoking is still now the main avoidable cause of disease, disability and mortality in industrialized countries. This habit is still very common in workplaces, where anti-smoke efforts seem to be less incisive than among general populations. The study analyzed the diffusion of smoke habit in 8111 male workers in Campania region, employed in different work activities (white collars, blue collars, drivers, cleaning civil servants, porters), so as to evaluate work related features, affecting its assumption and maintenance. Among all workers, smokers prevalence (42.7%) was higher than national male population. Percentages of smokers were highest among drivers (60.7%) and civil servants (52.5%), slightly lower among industry workers (47.3%) and lower among white collars (36.4%). The highest prevalence were found in 41-50 years age group (46.8%), but only among white collars aging was associated with higher smokers prevalence. Lower education degrees and two working variables, shifts and handwork, have been related with significantly smoking habit assumption. Results emphasized that health promotional programs are necessary to reduce smoke habit among workers, particularly among professionally and culturally unqualified subgroups.

[Not allergic dermatitis as occupational diseases: a suggestion for an evaluation method]. / La definizione della professionalità delle dermatiti non allergiche: proposta di un metodo di valutazione.

Aim of the study was to propose a method to define the relationship of not allergic contact dermatitis with chemical risk factors in workplace. This method evaluates the skin response to simultaneous chemical and mechanical stimulation, made with a soft bristle brush. The method has been used on 9 cases of not allergic skin diseases, observed from 2000 to 2006 in Occupational Medicine Division of "Federico II" University of Naples. The greatest part of pathologies had the polymorphous pattern of skin inflammation, characterized by subintrant erythema, suspected of occupational origin. In 6 cases a stronger reaction to both chemical and mechanical stimulation was highlighted, confirming a possible occupational etiology. In 1 case the occupational origin was excluded, while in 2 cases the skin response was uncertain. The method does not define all cases of occupational skin pathologies, but it seems to be very useful to diagnostic and insurance needs.

[Burnout: rising interest phenomenon in stressful workplace]. / Burnout: fenomeno di crescente interesse in ambienti di lavoro stressante.

Many stressful situations, particularly strong and long time lasting, can induce the burnout syndrome. The definition "burnout" refers to emotional and exhausting conditions related to working environment. Since 70'ties, many studies, have focused on this topic, have assessed that this condition is much more frequent in some particular professional categories: teachers, physicians, nurses, social workers, policemen, judges (the so-called helping professions). The main syndrome characteristics are: physical and emotional fatigue, depersonalization, frustration for unsuccessful professional realization and reduced personal accomplishment in competence and productivity with decreasing critical sense towards working field. The Maslach Burnout Inventory (MBI) has been the most popular instrument for measuring burnout in medical research. The coherence of many studies results on helping professions in different countries, leads to the conclusion that basically burnout is a psycho-social phenomenon of international relevance. These studies have also identified personal, relational and environmental risk factors susceptible to prevention.

Altered renal sodium handling and hypertension in men carrying the glucagon receptor gene (Gly40Ser) variant.

A higher prevalence of hypertension has been associated with the G-->A/GT (Gly40Ser) polymorphism of the glucagon receptor gene (GCGR) in two population studies. As the mutated receptor is less responsive to glucagon, it has been speculated that the increased susceptibility to hypertension is due to deprivation of the recognized natriuretic effect of the hormone. To test this hypothesis we determined the frequency of the polymorphic variant and evaluated the segmental renal sodium handling by the clearances of uric acid and of exogenous lithium in the Olivetti Heart Study participants (n=971). The polymorphic variant was present only in heterozygous form in 37 individuals (3.8%). After controlling for age and body mass index, the carriers of the variant were twice more likely to be hypertensive and almost three times more likely to be on antihypertensive treatment at the time of examination. Compared to participants carrying the wild type, those carrying the Gly40Ser allele had higher serum uric acid and lower fractional excretion of uric acid and exogenous lithium, independently of age, body mass, and current pharmacological treatment. We conclude that the Gly40Ser polymorphism of the GCGR gene is associated with higher risk of hypertension and with enhanced proximal tubular sodium reabsorption, a factor possibly contributing to hypertension in this group.

Red blood cell sodium-lithium countertransport and risk of future hypertension: the Olivetti Prospective Heart Study.

An elevated red blood cell (RBC) sodium-lithium countertransport (Na-Li CT) is associated with high blood pressure (BP) in cross-sectional investigations; however, its value as a predictor of future hypertension, and thus of cardiovascular risk, has not been defined. The present study evaluated the association between Na-Li CT and risk of future hypertension in a sample of 106 untreated normotensive middle-aged men participating in the Olivetti Prospective Heart Study in southern Italy. BP, anthropometric and metabolic variables, and RBC Na-Li CT were measured at baseline in 1987 and at a follow-up visit in 1994 through 1995. Na-Li CT was stable over time (r=0.85) and was significantly associated to systolic BP in both visits. Of the 106 initially normotensive participants, 14 were found to be hypertensive at the 8-year follow-up examination. Eleven of these 14 hypertensives were in the highest tertile of systolic BP at baseline, and 9 of 11 also had an elevated baseline Na-Li CT. In multiple logistic regression analysis, baseline BP, Na-Li CT, and age were all significant predictors of the risk of future hypertension. Individuals with baseline systolic BP in the highest tertile had a 60% risk of developing hypertension if their Na-Li CT was also high, whereas their risk was only 5% if Na-Li CT was in the two lowest tertiles (P=0.003). RBC Na-Li CT was a valuable predictor of subsequent hypertension in middle-aged men with a high-normal BP level for their age.

Body fat distribution and cardiovascular risk in middle-aged people in southern Italy.

Skinfold thickness, % body fat content, body mass index, systolic and diastolic blood pressure, plasma glucose, serum cholesterol and triglycerides have been measured in 132 middle-aged men (mean age 39.8 +/- 9.9, range 20-59 yr) and in 114 middle-aged women (mean age 39.1 +/- 9.3, range 20-59 yr). Anthropometric data were related to blood pressure and biochemical parameters by using a straight-line regression analysis. Body mass index, % body fat content, subscapular and suprailiac skinfold thickness, consideral as indicative of splanchnic fat distribution, were positively correlated to blood pressure, plasma glucose, cholesterol and triglycerides. Triceps skinfold thickness, an index of peripheral fat distribution, showed weaker or no correlation with these parameters. These preliminary observations in the Neapolitan area support the hypothesis that, in addition to body mass index and % body fat content, preferential splanchnic fat distribution is associated with cardiovascular risk factors.

Intestinal fatty acid binding protein polymorphism at codon 54 is not associated with postprandial responses to fat and glucose tolerance tests in healthy young Europeans. Results from EARS II participants.

UNLABELLED: Polymorphism Ala54Thr of the intestinal fatty acid-binding protein 2 (FABP2) has been reported to have an effect on the protein's affinity for long chain fatty acids and to be associated with serum lipid and insulin levels in fasting and especially postprandial states. We wanted to test whether this genetic variation is associated with fasting and postprandial glucose, insulin or lipid levels in 666 male university students participating in the second European Atherosclerosis Study (EARS II). We also studied whether the subgroup of 330 students with paternal history of myocardial infarction (MI) before the age of 55 have different genotype distribution than 336 matched controls. RESULTS: No difference in genotype distribution was observed between offspring with and without paternal history of MI or between populations from 11 European countries. The frequency of the threonine encoding allele was 0.276 in cases and 0.266 in controls. There were no differences in fasting or postprandial serum lipid, glucose or insulin levels between subjects having different genotypes. CONCLUSIONS: In this study FABP2 Ala54Thr polymorphism was not associated with lipid or glucose metabolism. In addition to environmental and genetic factors, selection of study population also may explain the difference between this and earlier studies.

Serum selenium and coronary heart disease risk factors in southern Italian men.

The association between serum selenium concentration and a number of coronary heart disease risk factors is studied in 364 males from southern Italy participating in the Olivetti Heart Study. Selenium correlates positively and significantly with serum cholesterol (r = 0.120; P = 0.022), and this positive association persists after adjustment for age and body mass index. Selenium levels in heavy smokers are lower than both light smokers and current non-smokers, but these differences do not reach statistical significance. Selenium is not significantly associated with any of the other CHD risk factors (e.g., triglycerides, HDL cholesterol, blood pressure, age, and body mass index). It is hypothesized that the association between selenium and serum cholesterol reported in this and previous studies could be due to dietary interrelationships between selenium intake and foods that affect serum cholesterol concentrations.

Blood lipids in Italy. Regional differences.

Serum cholesterol and triglyceride levels have been evaluated in samples from fasting males aged 20--59 in Northern (Brisighella), Central (Rome) and Southern (Pozzuoli) Italy. Regularly performed quality controls between laboratories assured comparability of data. A statisitically significant difference of mean serum cholesterol and triglyceride levels was observed for most age-groups in the 3 different areas, lower values being found in the southern population as compared to the central and northern ones. These results support previous findings and the thesis that large differences in blood lipid levels may still exist even within the same country and that they at least in part may be culturally determined in connection with different dietary habits.

A prospective study of hypertension and the incidence of kidney stones in men.

OBJECTIVE: To examine whether hypertension predicts the incidence of kidney stone disease. DESIGN: Prospective cohort study (the Olivetti Prospective Heart Study). SETTING: The Olivetti factory in Southern Italy. SUBJECTS: Five hundred and three male workers, aged 21 - 68 years, with no evidence of kidney stone disease at baseline. Follow-up 8 years. MAIN OUTCOME MEASURES: Anthropometry, blood pressure, biochemistry and history of kidney stone disease were evaluated at the baseline examination in 1987. Occurrence of kidney stone disease was evaluated again in 1994-1995. Hypertension was defined as systolic blood pressure > or = 160 or diastolic blood pressure, > or = 95 mmHg or both, or being on drug therapy for hypertension. Occurrence of kidney stone disease was defined as radiological or echographic evidence of calculi or documented passage of one or more stones. RESULTS: At baseline, 114/503 men (22.7%) had hypertension and 32 were on drug treatment. After 8 years, 52 (10.3%) incident cases of kidney stone disease were detected. The majority (n = 45) had a documented passage of one or more stones. The incidence of kidney stone disease was higher in hypertensive than in normotensive men (19/114 (16.7%) versus 33/389 (8.5%); P = 0.011). Hypertensive men had a greater risk of developing kidney stones than normotensive ones (RR 1.96; 95% confidence interval 1.16-3.32). The risk was unaffected by the exclusion of treated hypertensives (2.01; 1.13-3.59) and after adjustment for age (1.89; 1.12-3.18), body weight (1.78; 1.05-3.00) or height (2.00; 1.19-3.38). CONCLUSIONS: Hypertension in middle-aged men is a significant predictor of kidney stone disease rather than a consequence of renal damage caused by the kidney stones.

Relationship of the Trp64Arg polymorphism of the beta3-adrenoceptor gene to central adiposity and high blood pressure: interaction with age. Cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study.

METHODS: The association of the Trp64Arg polymorphism of the beta3-adrenoceptor (beta3-AR) gene with high blood pressure, central adiposity and other features of the metabolic syndrome was investigated in a large unselected sample of a white male working population in Southern Italy (n = 979). RESULTS: In the whole population, subjects heterozygous for the Trp64Arg mutation (11.2%) were not different from the homozygous Trp64Trp for any of the variables investigated. However, upon stratification for age, among men in the upper tertile of age (> 53 years), the Trp64Arg genotype was associated with higher waist: hip ratio (0.992 +/- 0.021 versus 0.982 +/- 0.037, P< 0.05), serum uric acid (6.34 +/- 1.50 versus 5.75 +/- 1.30 micromol/l, P < 0.05) and systolic blood pressure (144.3 +/- 19.4 versus 136.9 +/- 18.9 mmHg, P< 0.05) compared with the wild-type homozygotes. Accordingly, in the same age group, the carriers of Trp64Arg genotype were more often in the upper tertile of abdominal adiposity (69.7 versus 43.7%, P< 0.02) and serum uric acid (56.3 versus 34.8%, P < 0.02) and were more often hypertensive (68.6 versus 57.6%, P< 0.058) than the Trp64Trp homozygotes. No such differences were observed in younger age groups. No association was found with fasting serum insulin and the homeostasis model assessment (HOMA) index of insulin resistance. Furthermore, in a subgroup of 457 men for whom retrospective 20-year follow-up data were available, the variant genotype was associated with a higher probability of developing overweight (44.7 versus 27.0%, P < 0.05) and a trend to higher blood pressure (52.6 versus 38.4%, P = 0.09) over 20 years. CONCLUSION: We conclude that the Trp64Arg variant of the beta3-AR receptor predicts a greater tendency to develop abdominal adiposity and high blood pressure with advancing age.