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OBJECTIVE: High selenium status has been associated with adverse cardiometabolic outcomes in selenium-replete populations such as the US. In populations with lower selenium status such as in Italy, there is little epidemiological evidence about the association of selenium with cardiometabolic risk factors. We therefore examined cross-sectional and prospective relationships of serum selenium concentrations with cardiometabolic risk factors including blood pressure, diabetes and blood lipids in the Olivetti Heart Study. METHODS: The study population consisted of 445 adult male individuals for whom baseline serum selenium measurement and cardiometabolic risk factors at baseline (1994-1995) and follow-up examination (2002-2004: average follow-up=8 years) were available. Serum selenium was measured by atomic absorption spectrophotometry. RESULTS: Average serum selenium concentration at baseline was 77.5 ± 18.4 μg/L. In cross-sectional analyses, serum selenium levels were positively associated with serum total cholesterol (p for trend

The objective of the study was the evaluation of arterial stiffness, a cardiovascular risk factor, in patients with psoriatic arthritis (PsA). Twenty PsA patients classified on the basis of the CASPAR criteria (M/W, 14/6; mean age, 38.6 years; range, 22-53), attending our out-patient clinic, and 20 healthy control subjects (M/W, 14/6; mean age, 38.7 years; range, 22-53) matched for age, weight, height and with similar cardiometabolic profile entered the study. An exclusion criterion was the presence of known cardiovascular risk factors. Central hemodynamic parameters and aortic pulse wave velocity (aPWV) were assessed non-invasively by a SphygmoCor device. A significantly higher aPWV was recorded in PsA patients when compared to controls. The difference remained statistically significant after adjustment for age, weight, height, heart rate (HR) and central mean pressure (mean±SE; PsA, 8.3 ± 0.2 versus control, 6.8 ± 0.2 m/s; p < 0.0001). Among PsA patients, aPWV was related to known duration of disease (r = 0.63; p = 0.003). This result was confirmed after adjustment for the main confounders (β = 0.011; p = 0.013). These results support the concept of psoriatic disease as a systemic condition involving not only the skin, joints and gastrointestinal tract but also arterial vessels. The involvement of the vascular system indicates the presence of pathogenetic mechanisms that could accelerate the atherosclerotic process in this condition. © 2011 Clinical Rheumatology.

Aims To assess the relationship between duration of sleep and morbidity and mortality from coronary heart disease (CHD), stroke, and total cardiovascular disease (CVD). Methods and results We performed a systematic search of publications using MEDLINE (1966-2009), EMBASE (from 1980), the Cochrane Library, and manual searches without language restrictions. Studies were included if they were prospective, follow-up >3 years, had duration of sleep at baseline, and incident cases of CHD, stroke, or CVD. Relative risks (RR) and 95% confidence interval (CI) were pooled using a random-effect model. Overall, 15 studies (24 cohort samples) included 474 684 male and female participants (follow-up 6.9-25 years), and 16 067 events (4169 for CHD, 3478 for stroke, and 8420 for total CVD). Sleep duration was assessed by questionnaire and incident cases through certification and event registers. Short duration of sleep was associated with a greater risk of developing or dying of CHD (RR 1.48, 95% CI 1.22-1.80, P < 0.0001), stroke (1.15, 1.00-1.31, P = 0.047), but not total CVD (1.03, 0.93-1.15, P = 0.52) with no evidence of publication bias (P = 0.95, P = 0.30, and P = 0.46, respectively). Long duration of sleep was also associated with a greater risk of CHD (1.38, 1.15-1.66, P = 0.0005), stroke (1.65, 1.45-1.87, P < 0.0001), and total CVD (1.41, 1.19-1.68, P < 0.0001) with no evidence of publication bias (P = 0.92, P = 0.96, and P = 0.79, respectively). Conclusion Both short and long duration of sleep are predictors, or markers, of cardiovascular outcomes.

OBJECTIVES: The objective of this study was to assess the relation between the level of habitual potassium intake and the incidence of cardiovascular disease (CVD). BACKGROUND: Prospective cohort studies have evaluated the relationship between habitual potassium intake and incidence of vascular disease, but their results have not been not entirely consistent. METHODS: We performed a systematic search for prospective studies published, without language restrictions (1966 to December 2009). Criteria for inclusion were prospective adult population study, assessment of baseline potassium intake, assessment of vascular events as outcome, and follow-up of at least 4 years. For each study, relative risks (RRs) and 95% confidence intervals (CIs) were extracted and pooled using a random-effect model, weighted for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. RESULTS: Eleven studies were identified, providing 15 cohort samples that included 247,510 male and female participants (follow-up 5 to 19 years), 7,066 strokes, 3,058 coronary heart disease (CHD) events, and 2,497 total CVD events. Potassium intake was assessed by 24-h dietary recall (n = 2), food frequency questionnaire (n = 6), or 24-h urinary excretion (n = 3). In the pooled analysis, a 1.64-g (42 mmol) per day higher potassium intake was associated with a 21% lower risk of stroke (RR: 0.79; 95% CI: 0.68 to 0.90; p = 0.0007), with a trend toward lower risk of CHD and total CVD that attained statistical significance after the exclusion of a single cohort, based on sensitivity analysis (RR: 0.93; 95% CI: 0.87 to 0.99; p = 0.03 and RR: 0.74; 95% CI: 0.60 to 0.91; p = 0.0037). CONCLUSIONS: Higher dietary potassium intake is associated with lower rates of stroke and might also reduce the risk of CHD and total CVD. These results support recommendations for higher consumption of potassium-rich foods to prevent vascular diseases.

Objective To study the interaction between the C(-344)T CYP11B2 polymorphism and known determinants (age, body mass and dietary sodium) of blood pressure and plasma aldosterone. Design Cross-sectional and longitudinal (1980-1995) survey of male workers in southern Italy. Setting Medical centre of the Olivetti factories. Participants In 1995, the C(-344)T polymorphism was characterized in 811 untreated men. A subgroup of 280 participants already seen in 1980 was the object of longitudinal analysis. Main outcome measures Blood pressure, demographic, anthropometric and biochemical variables (serum and urinary electrolytes and plasma aldosterone) and frequency of the C(-344)T polymorphism. Results In the whole population, there was no difference among genotypes for any of the variables examined. However, multiple regression showed a significant interaction between age (but not body mass or sodium intake) and genotype with regard to systolic (P = 0.03) and diastolic (P= 0.02) pressure variability independently of covariates. Diastolic pressure increased linearly with age in carriers of the T allele (TT, P < 0.001 and TC, P = 0.005), but not in CC homozygotes (P= 0.848). In T carriers - but not in CC homozygotes - blood pressure and serum potassium increased and plasma aldosterone and serum sodium decreased across quintiles of age (P< 0.001 for all trends). In the longitudinal study, diastolic pressure increased significantly over time only in T carriers (TC+TT: +2.6 ± 0.6, versus CC: - 0.4 ± 1.5 mmHg, P= 0.04). Conclusion Inter-individual variation of blood pressure and plasma aldosterone is affected by the interaction of CYP11B2 C(-344)T polymorphism and ageing, thus supporting a role for this variant in mechanisms affecting blood pressure regulation.

Background: Urinary albumin excretion (UAE) is a predictor of chronic kidney disease and of higher cardiovascular morbidity and mortality. A number of studies investigated the effect of reduced dietary sodium intake on UAE but their results were not consistent. Therefore, our study assessed the effect of sodium restriction on UAE and/or on albumin/creatinine ratio (ACR) through an updated meta-analysis of the available randomised controlled trials (RCT). Methods: A systematic search of the on-line databases was conducted including RCTs that assessed UAE/ACR at the start and the end of the trial and outcomes expressed as difference between the effect of two different sodium intake regimens. For each study, the mean difference (MD) and 95% confidence intervals (95%CI) were extracted and pooled using a random effect model. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. Results: Nine studies were identified, providing 21 cohorts with overall 454 participants and 1-6 weeks follow-up time. In the pooled analysis, lower sodium intake was associated with a 26.7% (95% CI: -40.7 to -12.6) reduction of UAE, with no evidence of publication bias.The effect of lower sodium intake was highest in the cohorts including patients on concomitant RAAS-blocking therapy (-37.7%; -56.5 to -19.9), in those with intervention lasting at least 2 weeks (-32.4%; -47.2 to -17.7), and among participants with evidence of kidney damage (-32.6%; -47.5 to -17.6). The changes in BP occurring during intervention were a significant source of heterogeneity. >The analysis of changes in ACR, where available, provided similar results. Conclusions: This meta-analysis indicated that sodium intake reduction markedly reduces albumin excretion, more so among patients with hypertension and/or kidney damage and during concomitant RAAS-blocking therapy.

Background: Prospective cohort studies estimated the predictive role of exposure to coffee consumption and risk of hypertension (HP) or cerebrovascular disease, with contrasting results. Therefore, we carried out a meta-analysis to assess the relation between habitual coffee intake and risk of HP and stroke in the general population. Methods: We performed a systematic search for prospective studies published without language restrictions between 1966 and July 2013. Inclusion criteria were: original article, prospective design, adult general population study, assessment of coffee intake as baseline exposure, assessment of HP or stroke as outcome, and follow-up of at least 2 years. To evaluate risks of HP and stroke, relative risks and 95% confidence intervals for “low-moderate” (2-3 cups/d), “high”(4-6) and “very high”(>6) compared with “reference” (0-1) coffee intake categories were extracted and pooled using a random effect model. Heterogeneity, publication bias, subgroup and meta-regression analyses were performed. Results: Four studies for HP (171,460 participants and 39,851 HP diagnoses) and 10 for stroke (969,656 participants with 12,990 events) met the inclusion criteria. Coffee intake was assessed by dietary questionnaire. In pooled analyses, “low-moderate” and “high” coffee intake were both inversely associated with the risk of stroke (RR=0.84, 95% C.I. 0.78 to 0.91 and 0.83, 0.72 to 0.96, respectively) but not with risk of HP. “Very high” coffee intake was not significantly associated with either risk of stroke or of HP. There was significant heterogeneity between studies, while some evidence of publication bias was detected only in the analysis of HP risk. Sub-group analysis suggested an influence of gender and of geographic location, and meta-regression analysis detected age at baseline and length of follow-up as further sources of heterogeneity. Decaffeinated coffee consumption was not related to risk of stroke or HP. Conclusions: This meta-analysis of the available prospective studies showed that habitual coffee intake is not associated with higher risk of HP in the general population and that moderate-high coffee consumption is inversely associated with risk of stroke. A protective effect of coffee consumption towards cerebrovascular disease might be exerted through mechanisms independent of changes in blood pressure.

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/m2; 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.

A meta-analysis was performed of the effect of 3hydroxy3methylglutaryl-coenzyme A reductase inhibitors (statins) on blood pressure in humans including the randomized, controlled trials of statin therapy (20 trials and 828 patients) in which concomitant antihypertensive treatment (if any) remained unchanged throughout the study. A total of 291 and 272 patients were given a statin or placebo, respectively, in parallel group trials, whereas 265 took part in crossover trials receiving a statin and placebo (or probucol, in 1 trial). Systolic blood pressure was significantly lower in patients on statin than in those on placebo or control hypolipidemic drug (mean difference: -1.9 mm Hg; 95% CI: -3.8 to -0.1). The effect was greater when the analysis was restricted to studies with a baseline systolic blood pressure >130 mm Hg (Delta systolic blood pressure: -4.0; 95% CI: -5.8 to -2.2 mm Hg). There was a trend for lower diastolic blood pressure in patients receiving statin therapy compared with control: -0.9 mm Hg (95% CI: -2.0 to 0.2) overall and -1.2 mm Hg (95% CI: -2.6 to 0.1) in studies with a baseline diastolic blood pressure >80 mm Hg. In general, the higher the baseline blood pressure, the greater the effect of statins on blood pressure (P=0.066 for systolic blood pressure and P=0.023 for diastolic blood pressure). The blood pressure response to statins was unrelated to age, changes in serum cholesterol, or length of the trial. In conclusion, statin therapy has a relatively small but statistically significant and clinically meaningful effect on blood pressure.

We thank Zhou1 for his note on our meta-analysis of the effect of statin treatment on blood pressure. Zhou pointed out the potential impact of statin therapy on the imbalance between NO and reactive oxidative species production occurring in animal models of salt-sensitive hypertension.2 This ability of statins was indeed the basis for one of the explanations that we proposed for the relatively small but clinically meaningful antihypertensive effect of these drugs in humans.3 We share Zhou’s considerations and recollect the experimental evidence in support of the concept that genetic or acquired susceptibility to …

OBJECTIVE: The mechanisms underlying high blood pressure in the framework of metabolic syndrome (MS) are not clarified: we thus analyzed the relationship of MS and its components to renal tubular sodium handling among participants of the Olivetti Heart Study, an epidemiological investigation of a representative sample of adult white male population in southern Italy. METHODS: Proximal (FPRNa) and distal (FDRNa) fractional sodium reabsorption were estimated by the clearance of exogenous lithium in 702 participants aged 25-75 years examined in 1994-1995. Blood pressure and relevant anthropometric and biochemical variables were also measured. The diagnosis of MS was based on modified National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATP III) criteria. RESULTS: FPRNa, but not FDRNa, was directly associated with body mass index (BMI), waist circumference, diastolic pressure, serum triglyceride and uric acid, independently of age and of antihypertensive treatment. After adjustment for age, FPRNa, but not FDRNa, was significantly greater in individuals with MS, as compared to those without [77.6% (95% confidence interval = 76.7-80.1) versus 74.4% (73.7-75.1), P < 0.001]. A similar difference was observed after the exclusion of participants on current antihypertensive treatment (P = 0.018). In untreated individuals, a significant interaction was observed between obesity and insulin resistance as related to FPRNa (P = 0.002): the highest age-adjusted levels of FPRNa were detected in obese hypertensive and obese insulin-resistant participants. CONCLUSION: In this sample of an adult male population, MS was associated with an increased rate of FPRNa. This finding is relevant to the pathophysiology of MS and possibly to the prevention of its cardiovascular and renal consequences.

Humans began to use large amounts of salt for the main purpose of food preservation approximately 5,000 years ago and, although since then advanced technologies have been developed allowing drastic reduction in the use of salt for food storage, excess dietary salt intake remains very common. Gastric cancer is a common neoplasia, and dietary factors, including salt consumption, are considered relevant to its causation. A number of experimental studies supported the cocarcinogenic effect of salt through synergic action with Helicobacter pylori infection, in addition to some independent effects such as increase in the rate of cell proliferation and of endogenous mutations. Many epidemiological studies analyzed the relationship between excess salt intake and risk of gastric cancer. Both cross-sectional and prospective studies indicated a possibly dose-dependent positive association. In particular, a comprehensive meta-analysis of longitudinal studies detected a strong adverse effect of total salt intake and salt-rich foods on the risk of gastric cancer in the general population. Altogether, the epidemiological, clinical, and experimental evidence supports the possibility of a substantial reduction in the rates of gastric cancer through progressive reduction in population salt intake.

Objective: High selenium status has been associated with adverse cardiometabolic outcomes in seleniumreplete populations such as the US. In populations with lower selenium status such as in Italy, there is little epidemiological evidence about the association of selenium with cardiometabolic risk factors. We therefore examined cross-sectional and prospective relationships of serum selenium concentrations with cardiometabolic risk factors including blood pressure, diabetes and blood lipids in the Olivetti Heart Study. Methods: The study population consisted of 445 adult male individuals for whom baseline serum selenium measurement and cardiometabolic risk factors at baseline (1994–1995) and follow-up examination (2002–2004: average follow-up = 8 years) were available. Serum selenium was measured by atomic absorption spectrophotometry. Results: Average serum selenium concentration at baseline was 77.5 ± 18.4g/L. In cross-sectional analyses, serum selenium levels were positively associated with serum total cholesterol (p for trend

Objective: To assess the relation between the level of habitual salt intake and stroke or total cardiovascular disease outcome.\ud \ud Design: Systematic review and meta-analysis of prospective studies published 1966-2008.\ud \ud Data sources: Medline (1966-2008), Embase (from 1988), AMED (from 1985), CINAHL (from 1982), Psychinfo (from 1985), and the Cochrane Library.\ud \ud Review methods: For each study, relative risks and 95% confidence intervals were extracted and pooled with a random effect model, weighting for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. Criteria for inclusion were prospective adult population study, assessment of salt intake as baseline exposure, assessment of either stroke or total cardiovascular disease as outcome, follow-up of at least three years, indication of number of participants exposed and number of events across different salt intake categories.\ud \ud Results: There were 19 independent cohort samples from 13 studies, with 177 025 participants (follow-up 3.5-19 years) and over 11 000 vascular events. Higher salt intake was associated with greater risk of stroke (pooled relative risk 1.23, 95% confidence interval 1.06 to 1.43; P=0.007) and cardiovascular disease (1.14, 0.99 to 1.32; P=0.07), with no significant evidence of publication bias. For cardiovascular disease, sensitivity analysis showed that the exclusion of a single study led to a pooled estimate of 1.17 (1.02 to 1.34; P=0.02). The associations observed were greater the larger the difference in sodium intake and the longer the follow-up.\ud \ud Conclusions: High salt intake is associated with significantly increased risk of stroke and total cardiovascular disease. Because of imprecision in measurement of salt intake, these effect sizes are likely to be underestimated. These results support the role of a substantial population reduction in salt intake for the prevention of cardiovascular disease.

Background: The determinants of resistant hypertension (RH), defined as a blood pressure (BP) persistently above goal in spite of the concurrent use of 3 antihypertensive agents of different classes, remain largely unknown. We investigated the predictors of RH in 799 participants at the Olivetti Heart Study (OHS), mean age 51.5 yrs (SD±7.2) after an average follow-up period of 8 yrs. Methods: All participants attending the basal (1994 –95) and final (2002– 04) examination of the Olivetti Heart Study. A complete database including anthropometric, biochemical and ECG data was available for the analysis. Results: Among the 799 participants not affected by RH at basal examination, 497 (62.2%) were normotensive and 302 (37.8%) hypertensive. After 8 years, overall 29 subjects (3.6%) developed RH. Age, BMI, waist circumference, BP, Cornell Index, serum total cholesterol and uric acid, urinary fractional sodium excretion (FENa), a marker of dietary sodium intake, and albuminuria (ALB) were significantly higher (p Conclusions: Our results indicate that an early marker of organ damage (albuminuria), an elevated dietary sodium intake and a higher basal BP level were independent predictors of the development of RH in this sample of adult male population.

In his letter, Koh1 focused on the significant heterogeneity in the blood pressure (BP) effects of statins observed in the studies included in our meta-analysis2 and correctly identified a number of reasons that explain this large variability. Also, it should be underscored that very few of the trials available had the effect on BP as a specific outcome. In addition, Koh mentions the use of secondary sources, ie, published articles instead of primary data sets, as a potential source of bias. One may agree …

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.

Background: Paget’s disease of bone (PDB) is a common disorder characterised by increased, disorganised bone turnover in affected areas with overgrowth of immature woven bone. An increased cardiovascular risk has been reported in some studies of PDB, possibly related to arterial wall calcifications. The aim of this study was to evaluate central hemodynamic parameters and arterial stiffness in PDB patients. Methods: 11 PDB patients and 11 control subjects matched by age, weight, height and cardiovascular risk factors, were enrolled. Anthropometric measures, metabolic profile and information about PDB features (extension, therapy, and genetic alteration of disease) were made available for all subjects. Central hemodynamic parameters and carotid-femoral Pulse Wave Velocity (PWVcf) were assed non-invasively by Sphygmocor. Results: The PDB and the control group were comparable for age (PBD vs Control: 59±8.0 vs 58±7.2 yrs; M±SD, height: 168±6.7 vs 168±6.0cm and body weight: 78±14 vs 77±12kg). PBD patients presented a significantly higher PWVcf (9.8±1.8 vs 7.7±1.5m/s, p=0.008) and a trend toward higher central PP (48±19 vs 45±10 mmHg, p=0.60). The difference in PWVcf was confirmed after adjustment for age, gender, heart rate and central mean pressure (9.6±0.54 vs 7.18±0.53m/s M±SE; p=0.006). Conclusions: PDB patients presented evidence of higher arterial stiffness as compared with control subjects. These results support the hypothesis that PDB is a systemic condition associated with increased cardiovascular risk.