The role of HDL cholesterol in metabolic syndrome predicting cardiovascular events. The Gubbio population study.

BACKGROUND AND AIMS: Metabolic syndrome (MS) has recently been claimed to be an important new risk factor for the occurrence of coronary heart disease (CHD) and cardiovascular disease (CVD) events, although it is simply a combination of known risk factors used in a dichotomized fashion. The aims of this analysis were to explore the predictive role of MS for CHD and CVD events in a population study, in comparison with using the same factors in a continuous fashion, with special emphasis on HDL cholesterol. METHODS AND RESULTS: In the second examination of the Gubbio population study from central Italy, 2650 cardiovascular disease-free men and women, aged 35-74 years around 1990, were examined and followed-up for 12 years. The classic risk factors (sex, age, systolic blood pressure, serum cholesterol and smoking habits) were studied as predictors of CHD and CVD events, alone and with the contribution of other factors (HDL cholesterol, blood glucose, serum triglycerides and waist circumference) included in the so-called MS, based on several multivariate models. MS was also tested after adjustment for other risk factors. MS produced a predictive significant relative risk of 1.67 for CHD events and 1.82 for CVD events, but considering its single risk factors, the only ones contributing to prediction were HDL cholesterol and systolic blood pressure. Dedicated analyses showed that MS does not add anything to the power of prediction beyond the role of the single risk factors treated in a continuous fashion, while the best predictive power is obtained using classic risk factors (sex, age, smoking habits, total cholesterol, systolic blood pressure) with the addition of HDL cholesterol. CONCLUSIONS: The predictive power of MS is bound only to the presence of HDL cholesterol and blood pressure and does not add anything to using the same risk factor treated in a continuous fashion.

Modulation of BDNF and TrkB expression in rat hippocampus in response to acute neurotoxicity by diethyldithiocarbamate.

In this study, we examined the expression profile of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in adult rat hippocampus following acute administration of diethyldithiocarbamate (DDTC), a neurotoxic compound which was previously shown to induce microglia activation and cell death. Semiquantitative RT-PCR analysis detected significant variations of BDNF mRNA levels in whole hippocampus homogenates, with a peak at 24h after DDTC injection. Increased BDNF protein expression was demonstrated by immunohistochemistry in various hippocampal subfields. The most relevant increase was observed in the hilus of the dentate gyrus where BDNF levels at 120h were found to be almost four times those of basal levels. Full-length TrkB (TrkB.FL) encoding mRNA was also shown to undergo an earlier increase in the hippocampus of DDTC-treated rats. TrkB immunostaining with an antibody binding both full-length and truncated (TrkB.T) isoforms was found to increase at 120h in the hippocampal CA2 and CA3 regions. These results demonstrate that DDTC modulates the expression of BDNF and its receptor in the adult rat hippocampus and suggest a possible involvement of this neurotrophin in the protective response to DDTC-induced neuronal damage.

Expression of mRNA encoding neurotrophins and neurotrophin receptors in human granulocytes and bone marrow cells--enhanced neurotrophin-4 expression induced by LTB4.

The expression of neurotrophin and neurotrophin receptor mRNAs in human granulocytes and bone marrow cells was examined using ribonuclease protection assay and reverse transcription-polymerase chain reaction. The granulocytes expressed mRNA coding for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-4 (NT-4), but not neurotrophin-3 (NT-3). Moreover, the inflammatory mediator leukotriene B4 (LTB4) up-regulated the expression of NT-4 mRNA in granulocytes, but did not affect the expression of other neurotrophin mRNAs. Granulocytes generally lacked expression of mRNA coding for neurotrophin receptors. In contrast, human bone marrow cells consistently expressed mRNA for trkB (the BDNF and NT-4 receptor) and displayed variable expression of mRNA coding for trkA (the tyrosine kinase NGF receptor) and LNGFR (the low-affinity NGF receptor), whereas mRNA for trkC (the NT-3 receptor) was not expressed. Contrary to granulocytes, normal bone marrow cells generally expressed only low levels of mRNA encoding BDNF and NT-4. Expression of mRNA encoding NGF and NT-3 was not detected. However, significantly increased expression of BDNF mRNA was observed when bone marrow cells from patients with chronic myeloproliferative disorders (MPD) were analyzed. The results suggest that neurotrophins may act as granulocyte-derived effector molecules and that human bone marrow cells may be targets for these compounds, in particular BDNF and NT-4.

Microalbuminuria in nondiabetic adults: relation of blood pressure, body mass index, plasma cholesterol levels, and smoking: The Gubbio Population Study.

BACKGROUND: Evidence exists that cardiovascular risk factors influence progression toward end-stage renal failure. We tested the hypothesis that in nondiabetic middle-aged adults without macroalbuminuria, cardiovascular risk factors are related to urinary albumin excretion and prevalence of microalbuminuria, a sign of early nephropathy. METHODS: Cross-sectional analysis of data for 1567 participants in The Gubbio Population Study (677 men and 890 women), aged 45 to 64 years, without macroalbuminuria, without diabetes mellitus, and with fasting plasma glucose levels of less than 7.8 mmol/L (140 mg/ dL). Data collection included albumin and creatinine excretion in timed overnight urine collection; levels of fasting plasma cholesterol, glucose, triglycerides, creatinine, and uric acid; creatinine clearance; red blood cell sodium-lithium countertransport; blood pressure; weight; height; medical history; smoking status; and alcohol intake. Urinary albumin excretion and prevalence of microalbuminuria were the dependent variables. RESULTS: Blood pressure, plasma cholesterol levels, smoking, and body mass index significantly related to urinary albumin excretion and prevalence of microalbuminuria. In analyses with control for multiple variables, relative risk for microalbuminuria (urinary albumin excretion, 20-199 microg/min) in men and women was 2.51 and 1.62, respectively, with 18 mm Hg higher (1 SD) systolic blood pressure; 2.25 and 2.10, respectively, with 1.0-mmol/L (40 mg/dL) higher plasma cholesterol level; 1.99 and 1.91, respectively, for smokers vs nonsmokers; and 1.83 and 1.33, respectively, with 4 kg/m2 higher body mass index. Findings were similar for microalbuminuria defined as urinary albumin excretion of at least 25 microg/dL glomerular filtration rate. CONCLUSION: Major cardiovascular risk factors are independent correlates of microalbuminuria in nondiabetic middle-aged adults.

Sodium-lithium countertransport and blood pressure: the Gubbio Population Study.

The relation of red blood cell sodium-stimulated lithium countertransport to blood pressure (BP) and prevalence of hypertension was assessed in univariate and multivariate analyses for 2,748 men and women aged 25-74 years who participated in the baseline examination of the Gubbio Population Study in north central Italy. Since age-specific countertransport values were consistently higher for men than women, all analyses were done for men and women separately. In simple correlation analyses, countertransport was significantly related to systolic and diastolic BP in both sexes (r values 0.107-0.163). In age-adjusted analyses, countertransport was significantly related to BP level of both men and women not receiving antihypertensive treatment; mean levels were high for hypertensive persons receiving antihypertensive therapy compared with normotensive persons. Age-adjusted prevalence rates of hypertension were progressively higher for both sexes in successively higher quintiles of countertransport, almost twice as high for those in the highest quintile compared with those in the lowest quintile. Correspondingly, age-adjusted logistic regression analyses showed countertransport to be related significantly to prevalence of hypertension for both men and women (p less than 0.001). Since age, body mass index, plasma total cholesterol, uric acid, glucose, urinary sodium/potassium excretion, pulse, and (for men) daily alcohol intake also were significantly correlated with BP, and in some instances with countertransport, relation of countertransport to BP was also assessed in multivariate analyses with control for these variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium binding capacity of erythrocyte membrane in human hypertension.

The cell membrane calcium binding capacity of genetically hypertensive rats is reduced when measured in the presence of the submicromolar calcium concentrations proper of intracellular environment. The present work, performed as an ancillary study to an epidemiological survey on an entire population, aimed to investigate the existence of a similar abnormality in human hypertension. Calcium binding to the erythrocyte membrane was measured in clinically healthy normotensive (n = 12) and hypertensive individuals (n = 24). For this purpose, a filtration technique was used, based on the determination of 45Ca bound to the erythrocyte membrane in the presence of free calcium concentrations (40 nmol/l and 1 mumol/l), which are similar to those of the intracellular environment. The intra-assay technical error was determined on 35 duplicate samples and, when expressed as percent of the mean, was 24.1 at the 40 nmol/l concentration and 16.8 at the 1 mumol/l concentration. Membranes of untreated hypertensive patients, at both calcium concentrations, bound significantly less calcium than the control group. Treated and untreated hypertensive individuals had comparable values of membrane calcium binding capacity. Membranes of the treated hypertensive group bound less calcium than those of the normotensive group at both calcium concentrations, but the difference was statistically significant only in the presence of 40 nmol/l free calcium. A significant positive correlation was observed between the calcium binding capacity at 40 nmol/l concentration and that at 1 mumol/l in the treated and untreated hypertensive groups (r = 0.73 and 0.75, respectively; 0.51 for the normotensive group). These findings support the hypothesis that a cell membrane abnormality is detectable in some hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Hematocrit, blood pressure, and hypertension. The Gubbio Population Study.

Baseline data from the Gubbio Population Study in north central Italy were used to investigate the relation of hematocrit to blood pressure and hypertension among 2,809 men and women aged 25-74 years. Independent of gender, age, and other confounders, the hypertensive group had a higher hematocrit than the nonhypertensive group (p less than 0.001). In comparison with the untreated hypertensive group, the hypertensive group being treated with diuretics or with other drugs only had similar mean hematocrit levels despite significantly lower blood pressures. Hematocrit was positively correlated with systolic pressure (r = 0.085, p less than 0.01 and r = 0.264, p less than 0.001 for men and women, respectively) and diastolic pressure (r = 0.214, p less than 0.001 and r = 0.266, p less than 0.001). In both sexes, whether or not the treated hypertensive group was included, age-adjusted prevalence of hypertension and average blood pressure were higher for persons in higher quintiles of hematocrit (p less than 0.001). The association of hematocrit with blood pressure and hypertension was significant and independent of several confounders. The regression coefficient of blood pressure on hematocrit ranged between 0.410 and 0.620 mm Hg per unit of hematocrit for systolic pressure and between 0.371 and 0.581 for diastolic pressure, depending on gender and whether the treated hypertensive group was included in multiple regression analysis. Based on exponentiation of the multiple logistic coefficient, prevalence of hypertension was at least two times greater for persons whose hematocrit levels were higher by 10 units.

Prospective analysis of traits related to 6-year change in sodium-lithium countertransport. Gubbio Population Study Research Group.

Sodium-lithium countertransport (Na-Li CT) activity in red blood cells relates cross-sectionally and longitudinally to blood pressure and hypertension. Lifestyle and metabolic factors relate cross-sectionally to this sodium transporter. The aim of this study was to conduct a prospective analysis of 6-year Na-Li CT change and of traits related to Na-Li CT change. In 2183 participants in the Gubbio Population Study (972 men and 1211 women; baseline ages, 18 to 74 years), the following data collected at baseline and 6-year follow-up were analyzed: Na-Li CT; gender; age; body mass index (BMI); blood pressure; antihypertensive treatment; alcohol intake; smoking habits; urinary sodium-to-potassium ratio; and plasma cholesterol, glucose, uric acid, sodium, potassium, and triglycerides (measured only at follow-up). Six-year changes were defined as follow-up minus baseline values. Na-Li CT was higher at follow-up than at baseline in both genders (P<0.001). Baseline Na-Li CT; baseline and change values of BMI; and change values of alcohol intake, plasma potassium, and plasma glucose related to Na-Li CT change significantly and independently with control for other variables. Follow-up plasma triglyceride levels also related independently to Na-Li CT change. Coefficients were positive for BMI, alcohol intake, and plasma glucose and triglyceride levels and were negative for baseline Na-Li CT and plasma potassium levels. Baseline and change values of other variables did not relate significantly to Na-Li CT change. In conclusion, in prospective analyses, BMI, alcohol intake, plasma glucose, and lipids were directly related to Na-Li CT change; baseline Na-Li CT and plasma potassium levels were inversely related. The data support the concept that lifestyle and related metabolic factors influence Na-Li CT.

Hypertension, non-insulin-dependent diabetes, and intracellular sodium metabolism.

The present study was designed to investigate whether non-insulin-dependent diabetic hypertensive patients exhibit abnormalities in intracellular sodium metabolism similar to those described for essential hypertensive patients. Both normotensive and hypertensive non-insulin-dependent diabetic patients had similar average values of both Na+-Li+ countertransport and Na+-K+ cotransport compared with nondiabetic controls. Within the group of diabetic patients, hypertensive patients did not exhibit any abnormalities in either of the sodium transport pathways studied. The possible implications of these findings are addressed.

Sodium-lithium countertransport and blood pressure change over time: the Gubbio study.

Sodium-lithium countertransport activity in red blood cells relates to blood pressure (BP) and the prevalence of hypertension. This study investigated in adults the relation of sodium-lithium (Na-Li) countertransport to BP change from baseline to 6-year follow-up. In the Gubbio Population Study, 4210 men and women were 18 to 74 years old at baseline (1983-1986), and 3766 had a valid baseline Na-Li countertransport measurement; of these, 2729 were reexamined at 6 years of follow-up (1989-1992) and made up the study cohort. At baseline, data collection included age, height, weight, BP, pulse rate, drug treatment, alcohol intake, ratio of sodium to potassium in spot urine, plasma cholesterol, and Na-Li countertransport in red blood cells. At 6-year follow-up, data for age, BP, and drug treatment were collected as at baseline. From baseline, average BP declined for people on antihypertensive medication at follow-up and for those with baseline BP greater than or equal to 140/90 mm Hg (systolic/diastolic) and did not change or increased for the remaining participants. In quartile and correlation analyses controlled for sex, baseline BP, and antihypertensive treatment, BP change related significantly and directly to baseline Na-Li countertransport. In multiple linear regression analyses done for the entire cohort with control for other confounders, the regression coefficient of baseline Na-Li countertransport to BP change over time was positive and borderline significant. The Na-Li countertransport coefficient was positive and significant when analyses were done with the use of a categorical value of baseline Na-Li countertransport (quartile 4 and quartiles 1 through 3 combined). In both models, the Na-Li countertransport coefficient was the strongest for people with baseline BP greater than or equal to 120/80 mm Hg or for people with baseline age of 45 years or older. In conclusion, Na-Li countertransport significantly relates to BP change over time in adults.

Comparison of rofecoxib, celecoxib, and naproxen on renal function in elderly subjects receiving a normal-salt diet.

BACKGROUND: This study compared directly the renal effects of two selective cyclooxygenase (COX)-2 inhibitors (rofecoxib and celecoxib) with naproxen (dual COX-1/COX-2 inhibitor) and placebo in healthy elderly subjects on a sodium-replete diet. METHODS: A total of 67 elderly subjects stabilized in the clinic for weight and urinary sodium on a controlled 200-mEq sodium diet were randomized in a double-blind fashion to receive rofecoxib, 25 mg daily (n = 17); celecoxib, 200 mg twice daily (n = 17); naproxen, 500 mg twice daily (n = 17); or matching placebo (n = 16) for 28 days. Subjects were sequestered in the clinic for the first 14 treatment days on the controlled diet. RESULTS: Daily urinary sodium excretion during the first 72 hours of treatment (primary endpoint) significantly decreased in rofecoxib, celecoxib, and naproxen groups compared with baseline (P < or =.05). Rofecoxib and celecoxib decreases in urinary sodium excretion rates that were comparable with each other, on the basis of predefined boundaries (-39.5 versus -27.1 mEq/d, respectively) and to naproxen (-40.6, mEq/d). Rofecoxib, celecoxib, and naproxen increased mean systolic blood pressure to a similar degree (3.4, 4.3, and 3.1 mm Hg, respectively, versus -1.3 mm Hg for placebo) after 14 days of treatment; small changes also occurred in diastolic blood pressure (0.3, 0.8, and -0.4 mm Hg, respectively, versus -1.4 mm Hg for placebo). Changes from baseline in creatinine clearance, body weight, and urinary potassium excretion among active treatments were similar. After 28 days of treatment, findings were generally consistent with those at 14 days. No subject reported edema or discontinued treatment as the result of an adverse experience. CONCLUSION: In healthy elderly subjects on a sodium-replete diet, the COX-2 inhibitors rofecoxib and celecoxib did not differ from a nonselective nonsteroidal anti-inflammatory drug (naproxen), in influencing renal function as measured by urinary sodium excretion, systolic and diastolic blood pressure, creatinine clearance, or weight change.

Developmentally and wound-regulated expression of the gene encoding a cell wall copper amine oxidase in chickpea seedlings.

A chickpea cDNA encoding a cell wall copper amine oxidase (CuAO) was cloned and characterised. The 2010 bp open reading frame encodes a protein of 76.5 kDa which shares significant primary structure homology with other known CuAOs. Southern blot analysis indicates that in chickpea CuAO is encoded by a single gene or a small gene family. This cDNA was essential for studying the role of CuAO during seedling development and wound healing in chickpea seedlings. CuAO transcript level and activity were modulated during seedling development in parallel with cell maturation. Moreover, mechanical wounding induced a rapid increase of CuAO mRNA accumulation and enzyme activity which remained high during the wound-healing process. Aminoguanidine, a specific CuAO inhibitor, decreased the deposition of lignin-suberin barrier along the lesion. CuAO may be a limiting factor in H2O2 production in the cell wall of chickpea seedlings and its expression seems to integrate with the remodelling of plant cell wall occurring during ontogenesis and wound healing.

Effects of oral alendronate and intranasal salmon calcitonin on bone mass and biochemical markers of bone turnover in postmenopausal women with osteoporosis.

The main objective of this study was to determine the effect of daily oral alendronate treatment on bone mass in postmenopausal women affected by osteoporosis. The efficacy of intranasal salmon calcitonin was also examined. Nine centers in Italy enrolled 286 postmenopausal women between the ages of 48 and 76 with spinal bone mineral density > or = 2 SD below adult mean peak in the two-year, double-blind, randomized, placebo-controlled trial. Patients were randomized to one of four treatment arms: double-blind placebo, alendronate 10 mg/day, alendronate 20 mg/day, or open-label intranasal salmon calcitonin 100 IU/day; all patients received 500 mg Ca++ supplements. Bone mass was measured by dual-energy x-ray absorptiometry every six months for two years. Patients who received alendronate 10 or 20 mg experienced significant increases in bone mass at all sites measured. At the end of the second year, the mean percent changes, for alendronate 10 and 20 mg relative to placebo, were 5.2% and 7.3% at the lumbar spine, 3.8% and 4.6% at the femoral neck, and 7.1% and 7.5% at the trochanter, respectively. In contrast, intranasal salmon calcitonin failed to increase bone mineral mass significantly at any site. Both alendronate doses significantly decreased serum alkaline phosphatase, serum osteocalcin, and urinary pyridinolines, markers of bone turnover, whereas placebo and intranasal calcitonin did not. Alendronate was generally well tolerated and no serious adverse events were attributed to its use.(ABSTRACT TRUNCATED AT 250 WORDS)

Viral antibodies in oligoclonal and polyclonal IgG synthesized within the central nervous system over the course of mumps meningitis.

The occurrence of viral antibodies in relation to IgG separated by thin-layer polyacrylamide gel isoelectric focusing was studied in CSF and serum from 24 patients with mumps meningitis by immunofixation with viral antigens and autoradiography. Eleven of the patients displayed on the autoradiograms evidence of locally in the central nervous system synthesized mumps virus antibodies which were related to oligoclonal IgG bands in all 5 patients who displayed this CSF abnormality, otherwise to polyclonal IgG bands. Local synthesis of mumps virus antibodies was detectable in 43% of specimens obtained 1-13 days after onset, and in 75% obtained 27-47 days after onset. Only one patient displayed local synthesis of antibodies to other viruses (measles and herpes simplex) which could then be traced to polyclonal IgG bands.

Extended repertoire of specific antibodies in CSF of patients with subacute sclerosing panencephalitis compared to those with multiple sclerosis: anti-bacterial antibodies are also increased.

Serum and cerebrospinal fluid (CSF) from eight patients with subacute sclerosing panencephalitis (SSPE), 21 with multiple sclerosis (MS) and 16 controls were analyzed for IgG subclass pattern of anti-viral and anti-bacterial antibodies. In CSF of SSPE and MS patients IgG1 and IgG4 antibodies to measles and IgG1 to mumps were increased compared to the controls. In addition, the SSPE patients had elevated levels of IgG1 to PPD, teichoic acid, and to dextran in CSF. The group of MS patients had decreased levels of IgG1 antibodies to Staphylococcus aureus alpha-toxin.

Red blood cell sodium and potassium concentration and blood pressure. The Gubbio Population Study.

The relations of red blood cell sodium (RBC Na) and potassium (RBC K) concentrations to blood pressure and prevalence of hypertension were assessed for 1805 men and women, aged 25 to 74 years, who participated in the baseline examination of the Gubbio Population Study in north central Italy. In men, in univariate analyses, RBC Na concentration was not significantly related to systolic or diastolic blood pressure, while RBC K concentration was significantly and inversely related to blood pressure. In women RBC Na values correlated significantly and directly with systolic and diastolic pressure, but RBC K concentration was not significantly related to blood pressure. Results of the multivariate analyses indicated in men a significant independent and inverse relationship of RBC K concentration with hypertension and blood pressure, and in women a significant positive association of RBC Na concentration with hypertension. RBC Na did not relate independently to either systolic or diastolic blood pressure in men or women. Age-specific analyses suggested that the relationships between RBC K level and blood pressure in men and the relationship between RBC Na level and hypertension in women were stronger in older (age 55 to 74 years) compared to younger participants (25 to 54 years). These findings indicate that the associations of RBC Na and K concentrations and hypertension may be sex and age specific. The nature of these gender- and age-specific associations remains to be clarified. Prospective data are also needed for further clarification of the relation of intracellular Na metabolism to the etiology of hypertension.

Relation of urinary urea to blood pressure: interaction with urinary sodium.

A previous study reported that urinary markers of protein intake are inversely related to blood pressure via unknown mechanisms. In man and rats, protein intake affects renal function and increases renal sodium excretion. The present study investigates the relation between markers of protein intake and blood pressure and the possible role of sodium in this relation. Blood pressure status, overnight urinary urea as index of protein intake, urinary and plasma sodium, and other variables were measured in a population sample of 3705 men and women, aged 25-74 years, without high plasma creatinine. Urinary urea was inversely related to blood pressure and hypertension: in multivariate analyses, 6.5 mmol/h higher urinary urea (about one s.d. in men and women) was related to 4.25 mm Hg lower systolic blood pressure (95% confidence interval = 1.34-8.49), and to 0.65 lower risk of hypertension (95% CI 0.34-0.87). An interaction was found between overnight urinary sodium and the relation of urinary urea to blood pressure: the relation was significant only in persons with overnight urinary sodium above the median. Urinary urea was significantly and inversely also related to plasma sodium. Data confirm an inverse relation to blood pressure of protein intake as measured by urinary urea. The possibility of sodium-related mechanisms is supported by the interaction of urinary sodium with the relation and by the inverse association of urinary urea with plasma sodium. The hypothesis is made that high protein intake could counteract sodium-dependent blood pressure rise via stimulation of renal sodium excretion.

Elevated blood pressure and positive history of kidney stones: results from a population-based study.

Mild hypercalciuria has been observed in hypertension, but it is not yet established whether the prevalence of urinary stone disease is increased as well. Data from the cross-sectional phase of the Gubbio Study--a population-based survey on hypertension involving 5376 subjects (84% response rate)--have been analysed to address this issue, defining as hypertensive those subjects with diastolic pressure falling within the fifth quintile for each sex- and age-specific category, and/or under regular antihypertensive treatment. The prevalence of a positive history for urinary stone (radiographic and/or surgical evidence, and/or stone excretion) was increased by over 50% (P less than 0.01) in treated and untreated hypertensives. None of the 136 subjects with a positive urinary stone history were hypercalcaemic and none had renal failure.

Erythrocyte and platelet volume in human hypertension. The Gubbio Study Collaborative Group.

It has been reported that in rat and human hypertension the erythrocyte volume is reduced while platelet volume is increased. Data from the Gubbio Study, a population-based study involving over 5000 people (response rate greater than 84%), were analysed in order to address this issue among adult participants. The erythrocyte volume was significantly greater in male and female hypertensives compared with sex-matched normotensives. Female hypertensives also had a slightly but significantly reduced platelet volume while no significant difference in platelet volume was found between male hypertensives and male normotensives. Contrary to data from previous clinical studies based on small series of patients and controls, the findings of this study indicate a positive association between hypertension and erythrocyte volume.

Multiple risk factors in hypertension: results from the Gubbio study.

The association between hypertension and a number of cardiovascular disease risk factors was assessed in the large population sample of Gubbio, a town in central Italy that dates back to medieval times. The data confirm those of previous studies showing that hypertension is strongly associated with other metabolic abnormalities, such as markedly overweight subjects, hyperuricaemia, hyperglycaemia, hypercholesterolaemia, that may be related to the aetiopathogenesis of high blood pressure and, in addition, compound the risk of major clinical cardiovascular events in people with hypertension. The findings are therefore relevant for prevention strategies. In addition, the association between erythrocyte sodium-stimulated lithium countertransport and hypertension is being studied.