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Abstract

In patients with renal disease, an association between abnormal circadian blood pressure profile and abnormalities in bone and mineral metabolism, including vascular calcifications, is well known. However, such a link has not yet been reported in hypertensive patients with normal renal function. We aimed to evaluate if higher serum phosphate, calcium, parathyroid hormone (PTH) level and the calcium x phosphate (Ca x P) product would be associated with a nondipper hypertension, in patients with normal renal function and without any PTH disorder. 190 hypertensive subjects with the following inclusion criteria were enrolled: (1) normal phosphate and PTH levels; (2) glomerular filtration rate (GFR) >60 ml/min, and (3) no history of calcium, phosphate, vitamin D medication and hyperparathyroidism. Of the total population, 76 patients (40%) were classified as dippers and 114 (60%) as nondippers. Nondipper patients had higher levels of phosphate (3.70 +/- 0.61 vs. 3.35 +/- 0.44 mg/dl, p = 0.001), Ca x P product (35.4 +/- 6.5 vs. 31.5 +/- 5.0, p = 0.001) and PTH (75.7 +/- 28.8 vs. 46.6 +/- 17.1 pg/ml, p = 0.000) compared to dipper patients. Independent predictors (multiple regression) for nondipper hypertension were PTH (beta = 0.43, p = 0.001) and phosphate (beta = 0.9, p = 0.03). We demonstrate a graded independent relation between higher levels of phosphate, PTH, Ca x P product and the risk of nondipping in hypertensive patients with an estimated GFR of >60 ml/min and normal mineral metabolism. 2007 S. Karger AG, Basel

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Relation between serum phosphate level and cardiovascular event rate in people with coronary disease.

Marcello Tonelli, Frank Sacks, Marc Pfeffer … (2005)

Higher levels of serum phosphate are associated with adverse cardiovascular outcomes, especially in the setting of overt hyperphosphatemia. Given the biological importance of phosphorus, it is plausible that higher levels of serum phosphate within the normal range may also be associated with adverse outcomes. We performed a post hoc analysis of data from the Cholesterol And Recurrent Events (CARE) study. Baseline serum phosphate levels were measured in 4127 fasting participants who were randomized to receive pravastatin 40 mg daily or placebo and followed up for a median of 59.7 months. We used Cox proportional-hazards models to examine the association between serum phosphate and adverse clinical outcomes after adjustment for potential confounders. During nearly 60 months of follow-up, 375 participants died. A significant association was noted between baseline serum phosphate level and the age-, race-, and sex-adjusted risk of all-cause death (hazard ratio per 1 mg/dL, 1.27; 95% confidence interval, 1.02 to 1.58). After categorization based on baseline phosphate level ( or =4 mg/dL) and further adjustment, a graded independent relation between phosphate and death was observed (P for trend=0.03). For instance, participants with serum phosphate > or =3.5 mg/dL had an adjusted hazard ratio for death of 1.27 (95% confidence interval, 1.02 to 1.59) compared with those with serum phosphate of <3.5 mg/dL. Higher levels of serum phosphate were also associated with increased risk of new heart failure, myocardial infarction, and the composite of coronary death or nonfatal myocardial infarction, but not the risk of stroke. We found a graded independent relation between higher levels of serum phosphate and the risk of death and cardiovascular events in people with prior myocardial infarction, most of whom had serum phosphate levels within the normal range. Given the ready availability and low cost of serum phosphate assays, this finding may prove clinically useful.

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Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems.

Xinmin Li, S. Chen, Wenhua Liu … (2004)

Our recent studies suggest that 1,25-dihydroxyvitamin D3 functions as an endocrine suppressor of renin biosynthesis. Genetic disruption of the vitamin D receptor (VDR) results in overstimulation of the renin-angiotensin system (RAS), leading to high blood pressure and cardiac hypertrophy. Consistent with the higher heart-to-body weight ratio, the size of left ventricular cardiomyocytes in VDR knockout (KO) mice was markedly increased compared with wild-type (WT) mice. As expected, levels of atrial natriuretic peptide (ANP) mRNA and circulating ANP were also increased in VDRKO mice. Treatment of VDRKO mice with captopril reduced cardiac hypertrophy and normalized ANP expression. To investigate the role of the cardiac RAS in the development of cardiac hypertrophy, the expression of renin, angiotensinogen, and AT-1a receptor in the heart was examined by real-time RT-PCR and immunostaining. In VDRKO mice, the cardiac renin mRNA level was significantly increased, and this increase was further amplified by captopril treatment. Consistently, intense immunostaining was detected in the left ventricle of captopril-treated WT and VDRKO mice by use of an anti-renin antibody. Levels of cardiac angiotensinogen and AT-1a receptor mRNAs were unchanged in the mutant mice. These data suggest that the cardiac hypertrophy seen in VDRKO mice is a consequence of activation of both the systemic and cardiac RAS and support the notion that 1,25-dihydroxyvitamin D(3) regulates cardiac functions, at least in part, through the RAS.

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Calcium, phosphate, and parathyroid hormone levels in combination and as a function of dialysis duration predict mortality: evidence for the complexity of the association between mineral metabolism and outcomes.

Michael Stevens, Craig Cameron, S Cardew … (2004)

Current literature suggests associations between abnormal mineral metabolism (MM) to cardiovascular disease in dialysis populations, with conflicting results. MM physiology is complex; therefore, it was hypothesized that constellations of MM parameters, reflecting this complexity, would be predictive of mortality and that this effect would be modified by dialysis duration (DD). Prevalent dialysis patients in British Columbia, Canada, who had measurements of calcium (Ca), phosphate (Pi), and parathyroid hormone (iPTH) between January and March 2000 were followed prospectively until December 2002. Statistical analysis included Cox proportional hazard models with Ca, Pi, and iPTH alone and in combination as explanatory variables; analyses were stratified by DD. The 515 patients included in this analysis represent British Columbia and Canadian dialysis populations: 69% were on hemodialysis, mean age was 60 +/- 17 yr, 40% were female, and 34% had diabetes. Mean Ca and Pi values were 2.32 +/- 0.22 mmol/L and 1.68 +/- 0.59 mmol/L, respectively, and median iPTH was 15.8 pmol/L (25th to 75th percentile: 6.9 to 37.3 pmol/L). Serum Pi, after adjusting for demographic, dialysis type and adequacy, hemoglobin, and albumin, independently predicted mortality (risk ratio [RR], 1.56 per 1 mmol/L; 95% confidence interval [CI], 1.15 to 2.12; P = 0.004). When combinations of parameters were modeled (overall P = 0.003), the combinations of high serum Pi and Ca with high iPTH (RR, 3.71; 95% CI, 1.53 to 9.03; P = 0.004) and low iPTH (RR, 4.30; 95% CI, 2.01 to 9.22; P < 0.001) had highest risks for mortality as compared with the combination of high iPTH with normal serum Ca and Pi that had the lowest mortality and was used as index category. These effects varied across different strata of DD. This analysis demonstrates the importance of examining combinations of MM parameters as opposed to single variables alone and the effect of DD. In so doing, the complex interaction of time and MM can begin to be understand. Further exploration is required.

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PubMed ID:: 17703091

DOI:: 10.1159/000107489

ScienceOpen disciplines: Chemistry

Keywords: Adult,Aged,Blood Pressure,Blood Pressure Monitoring, Ambulatory,Calcium,blood,Circadian Rhythm,Female,Glomerular Filtration Rate,Humans,Hypertension,diagnosis,physiopathology,Kidney,Male,Middle Aged,Parathyroid Hormone,Phosphates

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Relation between serum calcium, phosphate, parathyroid hormone and 'nondipper' circadian blood pressure variability profile in patients with normal renal function.

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Karger: Nephrology

Most cited references 14

Relation between serum phosphate level and cardiovascular event rate in people with coronary disease.

Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems.

Calcium, phosphate, and parathyroid hormone levels in combination and as a function of dialysis duration predict mortality: evidence for the complexity of the association between mineral metabolism and outcomes.

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