Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that ...increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 95% CI, 1.21–1.93) or CVM (hazard ratio, 2.08 95% CI, 1.146–2.97; P<0.001). Cutoff values of SUA able to discriminate total mortality (4.7 mg/dL 95% CI, 4.3–5.1 mg/dL) and CVM status (5.6 mg/dL 95% CI, 4.99–6.21 mg/dL) were identified. The information on SUA levels provided a significant net reclassification improvement of 0.26 and of 0.27 over the Heart Score risk chart for total mortality and CVM, respectively (P<0.001). Sex-specific cutoff values for total mortality and CVM were also identified and validated. In conclusion, SUA levels increasing the risk of total mortality and CVM are significantly lower than those used for the definition of hyperuricemia in clinical practice. Our data provide evidence of a cardiovascular SUA threshold that might contribute in clinical practice to improve identification of patients at higher risk of CVM.
OBJECTIVE:The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of ...serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men.
METHODS:The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18–95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months.
RESULTS:A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096–1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105–2.075, P < 0.01), but not in men.
CONCLUSION:The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.
IMPORTANCE The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated ...glomerular filtration rate GFR of −57% or greater) is a late event. OBJECTIVE To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION Individual meta-analysis of 1.7 million participants with 12 344 ESRD events and 223 944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. DATA EXTRACTION AND SYNTHESIS Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. RESULTS The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% 95% CI, 6.4%-7.4% of the entire consortium) were more common than changes of −57% (0.79% 95% CI, 0.52%-1.06%). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. CONCLUSIONS AND RELEVANCE Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
OBJECTIVE:To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and ...Cardiovascular Risk of the Italian Society of Hypertension.
METHODS:The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18–95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders.
RESULTS:A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all hazard ratio 1.29 (1.23–1.359), P < 0.0001 and fatal hazard ratio 1.268 (1.121–1.35), P < 0.0001 incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole databaseSUA more than 5.34 mg/dl (confidence interval 4.37–5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78–5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284–2.109, P < 0.0001) for all heart failure and 1.645 (1.284–2.109, P < 0.0001) for fatal heart failure, respectively.
CONCLUSION:The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).
Summary Background Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease. However, whether the association of the kidney disease measures, estimated glomerular ...filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status is unknown. Methods We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and ESRD associated with eGFR and albuminuria in individuals with and without hypertension. Findings We analysed data for 45 cohorts (25 general population, seven high-risk, and 13 chronic kidney disease) with 1 127 656 participants, 364 344 of whom had hypertension. Low eGFR and high albuminuria were associated with mortality irrespective of hypertensive status in the general population and high-risk cohorts. All-cause mortality risk was 1·1–1·2 times higher in individuals with hypertension than in those without hypertension at preserved eGFR. A steeper relative risk gradient in individuals without hypertension than in those with hypertension at eGFR range 45–75 mL/min per 1·73 m2 led to much the same mortality risk at lower eGFR. With a reference eGFR of 95 mL/min per 1·73 m2 in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min per 1·73 m2 was 1·77 (95% CI 1·57–1·99) in individuals without hypertension versus 1·24 (1·11–1·39) in those with hypertension (p for overall interaction=0·0003). Similarly, for albumin-creatinine ratio of 300 mg/g ( vs 5 mg/g), HR was 2·30 (1·98–2·68) in individuals without hypertension versus 2·08 (1·84–2·35) in those with hypertension (p for overall interaction=0·019). We recorded much the same results for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, did not differ by hypertensive status. Results for chronic kidney disease cohorts were similar to those for general and high-risk population cohorts. Interpretation Chronic kidney disease should be regarded as at least an equally relevant risk factor for mortality and ESRD in individuals without hypertension as it is in those with hypertension. Funding US National Kidney Foundation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The World Health Organization recommends a minimum requirement of 0.8 g/day protein/kg ideal weight. Low protein diets are used against kidney failure progression. Efficacy and safety of these diets ...are uncertain. This paper reviews epidemiological studies about associations of protein intake with kidney function decline and mortality. Three studies investigated these associations; two reported data on mortality. Protein intake averaged >60 g/day and 1.2 g/day/kg ideal weight. An association of baseline protein intake with long-term kidney function decline was absent in the general population and/or persons with normal kidney function but was significantly positive in persons with below-normal kidney function. Independent of kidney function and other confounders, a J-curve relationship was found between baseline protein intake and mortality due to ≈35% mortality excess for non-cardiovascular disease in the lowest quintile of protein intake, a quintile where protein intake averaged <0.8 g/day/kg ideal weight. Altogether, epidemiological evidence suggests that, in patients with reduced kidney function, protein intakes of ≈0.8 g/d/kg ideal weight could limit kidney function decline without adding non-renal risks. Long-term lower protein intake could increase mortality. In most patients, an intake of ≈0.8 g/day/kg would represent a substantial reduction of habitual intake considering that average intake is largely higher.
The present study investigated cardiovascular calcification, peripheral bone mineral density (BMD), and lab indices in hypertensive patients aged 55-74 years without severe kidney dysfunction. ...Cardiovascular calcification was investigated by ultrasound examinations at eight sites: aortic valve, left and right common carotid artery, left and right carotid artery bifurcation, left and right internal carotid artery, and abdominal aorta. The presence/absence of calcification at each site was coded as 1/0, respectively, for the calculation of a cumulative score. Peripheral bone mineral density was assessed by forearm quantitative computed tomography (pQCT) and was defined as low if the T-score was <-1. Lab work-up included plasma creatinine, calcium, phosphorus, parathyroid hormone and 25-(OH) vitamin D measurements. Ninety-one patients were studied. The range was 2-8 for the calcification score and 229-492 mg cm
for bone mineral density. The prevalence of low bone densitometry was 83.5%. The calcification score and bone densitometry were inversely correlated in a non-adjusted analysis (R=-0.297, P=0.004) and in multivariable regression (beta=-0.335, P=0.003). The association was significant for subcortical bone (beta=-0.302, P=0.007) but not for cortical bone or trabecular bone (P⩾0.194 in both cases). The calcification score was associated with a low prevalence of bone densitometry in the non-adjusted analysis (odds ratio=2.53, 95% CI=1.41/4.54, P=0.002) and in the multivariable logistic regression (odds ratio=2.46, 95% CI=1.25/4.81, P=0.009). Cardiovascular calcification was independently associated with peripheral bone densitometry in hypertensive patients. The data support the hypothesis that vascular calcification and low bone densitometry share some determinants in hypertensive patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background: Lower physical activity, lower alcohol intake, higher protein intake, higher sodium intake, and lower potassium intake related to greater kidney function decline over time, according to ...previous studies. The present study aimed to analyze the cumulative effects of these factors. Methods: This prospective, observational, population-based cohort study included 3039 adult examinees of the Gubbio study who participated in the baseline exam and 15-year follow-up exam. Kidney function was evaluated as estimated glomerular filtration rate (eGFR). Habitual physical activity in leisure time and habitual alcohol intake were assessed by questionnaires; dietary intakes of protein, sodium, and potassium were assessed by urinary markers. Based on previous reports, each one of the five modifiable factors was scored 0 for the tertile associated with smaller eGFR decline (low risk), 2 for the tertile associated with greater eGFR decline (high risk), and 1 for the intermediate tertile (intermediate risk). A cumulative score was calculated as the sum of the factor-specific scores and used as the main independent variable. Results: The cumulative score ranged from 0 to 10, that is, from low risk for all factors to high risk for all factors (skewness = 0.032, mean ± SD = 5 ± 2). To avoid the bias of low-n analyses, score 0 was re-coded as 1 and score 10 was recoded as 9; after re-coding, the cumulative score ranged from 1 to 9 (skewness = 0.016, mean ± SD = 5 ± 2). The cumulative score related to annualized eGFR change in multi-variable linear regression (slope = −0.027, 95%CI = −0.039/−0.014, p < 0.001); findings were consistent in apparently healthy examinees and other subgroups. De novo incidence of eGFR < 60 mL/min × 1.73 m2 was higher along the cumulative score (p < 0.001). Compared to score 1 (n examinees = 35, adjusted incidence = 2.0%), incidence of low kidney function was 4.5 times higher in score 5 (n examinees = 624, adjusted incidence = 8.9%) and 6.5 times higher in score 9 (n examinees = 86, adjusted incidence = 12.9%). The cumulative score related to incidence of low kidney function in multi-variable logistic regression (odds ratio = 1.19, 95%CI = 1.08/1.32, p < 0.001). Conclusions: The combination of five modifiable factors predicted large differences in long-term incidence of low kidney function.
The pathophysiological mechanisms underlining constipation are incompletely understood, but prolonged bed rest is commonly considered a relevant determinant.
Our primary aim was to study the effect ...of long-term physical inactivity on determining a new onset of constipation. Secondary aim were the evaluation of changes in stool frequency, bowel function and symptoms induced by this prolonged physical inactivity.
Ten healthy men underwent a 7-day run-in followed by 35-day study of experimentally-controlled bed rest. The study was sponsored by the Italian Space Agency. The onset of constipation was evaluated according to Rome III criteria for functional constipation. Abdominal bloating, flatulence, pain and urgency were assessed by a 100mm Visual Analog Scales and bowel function by adjectival scales (Bristol Stool Form Scale, ease of passage of stool and sense of incomplete evacuation). Daily measurements of bowel movements was summarized on a weekly score. Pre and post bed rest Quality of Life (SF-36), general health (Goldberg's General Health) and depression mood (Zung scale) questionnaires were administered.
New onset of functional constipation fulfilling Rome III criteria was found in 60% (6/10) of participants (p=0.03). The score of flatulence significantly increased whilst the stool frequency significantly decreased during the week-by-week comparisons period (repeated-measures ANOVA, p=0.02 and p=0.001, respectively). Stool consistency and bowel symptoms were not influenced by prolonged physical inactivity. In addition, no significant changes were observed in general health, in mood state and in quality of life at the end of bed rest.
Our results provide evidence that prolonged physical inactivity is relevant etiology in functional constipation in healthy individuals. The common clinical suggestion of early mobilization in bedridden patients is supported as well.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
: Adults with celiac disease (CeD) show low bone mineral density (BMD) and high fracture risk. CeD guidelines suggest measurements of serum minerals and vitamin D. However, studies on vitamin levels ...in CeD patients are contradictory.
: To investigate in CeD, 25-hydroxy-vitamin D 25(OH)D, 1,25-dihydroxy-vitamin D 1,25(OH)2D, and related analytes and to evaluate their relationships to peripheral BMD as assessed by peripheral quantitative computed tomography (pQCT).
: Gluten-free diet (GFD)-treated, and untreated adult CeD patients naïve to vitamin D and calcium supplementation underwent measurements of serum 25(OH)D, 1,25(OH)2D, parathyroid hormone (PTH), total calcium, phosphate, and of radius BMD by pQCT.
: Complete data were collected in 105 patients for lab tests and 87 patients for BMD. For lab tests, untreated CeD differed from treated CeD for 22.0% lower serum 25(OH)D (
= 0.023), 42.5% higher serum PTH (
< 0.001), and 13.0% higher serum 1,25(OH)2D (
= 0.029) in the presence of similar serum calcium and phosphorus (
> 0.35). For BMD, untreated CeD differed from treated CeD for lower diaphyseal cortical BMD (1133 and 1157 mg/cm
,
= 0.004) but not for distal BMD (total, trabecular, and subcortical,
> 0.13). Independent correlates of diaphyseal cortical BMD were GFD treatment and body mass index (
< 0.05).
: Data indicated that, compared to CeD patients on a gluten-free diet, untreated adult CeD patients at diagnosis had lower 25(OH)D, higher PTH, and higher 1,25(OH)
D in the absence of difference in serum calcium and phosphorus. 25(OH)D and 1,25(OH)
D, even below the normal range, were not associated with BMD. Our findings do not support the use of vitamin D supplementation for all CeD adults.
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