Phosphate supplements are considered safe if taken as prescribed. Medicines that interact with hydralazine may either decrease its effect, affect how long … High phosphorus and calcium levels also lead to dangerous calcium deposits in blood vessels, lungs, eyes, and heart. Baseline characteristics of study participants are shown in Table 1. This hypothesis is supported by data indicating that diet-induced reductions in serum phosphate levels lead to increased calcitriol levels in healthy men.22,23 Because no information on 25-hydroxyvitamin D or calcitriol levels was available to us, however, this hypothesis requires further study. You may also obtain it from nuts, legumes and cereals. Your phosphorus levels can get too high when your kidneys aren’t working correctly. Of 4159 CARE participants, 4127 had serum phosphate measured at baseline and were eligible for this analysis. Overall, there was a direct association between GFR and serum phosphate levels, but stratified analyses showed that serum phosphate was inversely correlated with kidney function when baseline GFR was <60 mL/min/1.73 m2 and directly correlated with kidney function when baseline GFR was ≥60 mL/min/1.73 m2. The small numbers of subjects with levels of serum phosphate in the lowest and highest categories probably contributed to the nonsignificant relation between serum phosphate (as a continuous variable) and outcome, because tests for trend were significant when phosphate was treated as a categorical variable. Curves show the survivor function for each stratum of baseline serum phosphate using the mean of covariates method. A final consideration is that higher serum phosphate levels might indicate impaired kidney function, even after adjustment for estimated GFR, and that severity of renal disease rather than phosphate levels per se might account for the apparent association between higher serum phosphate and adverse clinical outcomes.24 We used an equation based on serum creatinine to estimate kidney function that is recommended by authorities12 but nevertheless has some limitations.25,26 Although we did not perform a gold standard measurement of GFR such as iothalamate clearance, our results were similar when alternative indices of kidney function were used and after exclusion of those with evidence of impaired GFR at baseline, making it less likely that our findings were confounded by the presence of renal insufficiency. Multivariate linear regression was used to determine factors associated with baseline serum phosphate levels. 142, Issue Suppl_4, November 17, 2020: Vol. One reason this can happen is that elevated phosphorus levels reduce your body's ability to make vitamin D, which in turn leads to calcification in your heart's blood vessels. Finally, we forced additional variables that could conceivably be associated with either exposure or outcome (baseline diuretic use, pravastatin use, serum calcium, and proteinuria) into the adjusted model; they did not appreciably affect results (data not shown). 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. The risk of stroke was not significantly increased in participants with serum phosphate ≥4 mg/dL compared with those with serum phosphate of 2.5 to 3.4 mg/dL (adjusted HR, 0.93; 95% CI, 0.46 to 1.85). The demographic characteristics of these remaining participants are shown in Table 1. These characteristics were forced into the adjusted model presented above but did not appreciably affect the association between higher levels of serum phosphate and the increased risk of death (P for trend=0.047), new heart failure (P for trend=0.02), fatal or nonfatal myocardial infarction (P for trend=0.04), the composite of fatal coronary disease or nonfatal myocardial infarction (P for trend=0.04), or stroke (P for trend=0.33). Participants with serum phosphate ≥4 mg/dL had a fully adjusted HR for experiencing the composite outcome of coronary death or nonfatal myocardial infarction of 1.32 (95% CI, 0.95 to 1.84) compared with those with serum phosphate of 2.5 to 3.4 mg/dL. Several recent studies demonstrate that higher levels of phosphate are associated with an increased risk of all-cause and cardiovascular death when kidney function is impaired, especially in people with end-stage renal disease.6–9 Vascular calcification has been postulated as the link between hyperphosphatemia and adverse outcomes in the setting of kidney disease, perhaps accelerated by abnormal calcium levels and hyperparathyroidism.5,16 However, unlike participants in the present trial (only 5.2% of whom had hyperphosphatemia at baseline), many of the subjects in these previous studies had overt hyperphosphatemia or were receiving medications that may have influenced the association between serum phosphate and outcome. A significant association was noted between baseline serum phosphate level and the age-, race-, and sex-adjusted risk of all-cause death (hazard ratio [HR] per 1 mg/dL, 1.27; 95% CI, 1.02 to 1.58; P=0.03; Table 3). Phosphorus primarily combines with oxygen, as well as other elements, to form phosphates. For instance, participants with serum phosphate ≥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. It is available in a wide variety of foods, including meat, fish, dairy, and some vegetables. Unauthorized Normal range is 3.7 to 5.2 mEq/L (3.7 to 5.2 mmol/L). Guest editor for this article was Donna K. Arnett, MD. Download figureDownload PowerPointFigure 2. Imbalances may disrupt your metabolism and raise your risk of chronic diseases. To keep your heart healthy, the amount of salt you ingest may be restricted to 1500 mg (1.5 g) per day. If your kidneys don't work well, you can develop a high phosphorus level in your blood, putting you at greater risk of heart disease, weak bones, joint pain and even death. Potassium is an essential mineral, meaning that your body must obtain it from your diet. Higher levels of serum phosphate were associated with an increased risk of new heart failure after adjustment for age, sex, and race (P for trend=0.02; Table 3) and in the model (P for trend=0.03; Table 3). Despite the importance of phosphate for diverse cellular and physiological functions, little information describes the relation between serum phosphate and clinical outcomes. E-mail. The following reactions can occur: Body As A Whole: Ischemic injury due to potent vasoconstrictor action and tissue hypoxia. Linus Pauling Institute Micronutrient Center: Phosphorus, University of Maryland Medical Center: Phosphorus, Eastern Michigan University: Control of Blood Pressure, Vitamins & Minerals That Affect the Heart. In sensitivity analyses, we adjusted for additional baseline factors found to be associated with serum phosphate levels in the current data set (alcohol use, country of treatment, use of β-adrenergic blockers, systolic blood pressure). TABLE 2. Having too much phosphorus in your blood is also called hyperphosphatemia. This substudy on serum phosphate was not financially supported by industry. A graded association was noted between baseline level of serum phosphate and the adjusted risk of all-cause mortality, development of heart failure or fatal or nonfatal myocardial infarction, and the composite outcome of fatal coronary disease or nonfatal myocardial infarction (all P for trend=0.03; Figure 1 and Figure 2). Some of the richest phosphorus sources include dairy products, meat and fish. Although we did not have data on parathyroid hormone levels, we controlled for estimated GFR and for other factors that might be associated with hyperparathyroidism such as serum calcium and albumin. During nearly 60 months of follow-up, 375 participants died. Participants with serum phosphate ≥4 mg/dL had a fully adjusted HR for experiencing myocardial infarction of 1.50 (95% CI, 1.05 to 2.16) compared with those with serum phosphate of 2.5 to 3.4 mg/dL. Other blood tests may be … Given the ready availability and low cost of serum phosphate assays, this finding may prove clinically useful. This is for an otherwise healthy person. It is also an electrolyte, a substance that helps conduct electricity in the body. We used Cox proportional-hazards models to examine the association between serum phosphate and adverse clinical outcomes after adjustment for potential confounders. This can also cause your calcium levels to rise. HRs have been adjusted for age, sex, race, smoking status, diabetic status, waist-to-hip circumference ratio, fasting glucose, GFR hemoglobin, serum albumin, aspirin use, and left ventricular ejection fraction (all at baseline). What Is the Main Function of Phosphorus in the Body? Learn more about its benefits here. Local Info Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB), Journal of the American Heart Association (JAHA), Customer Service and Ordering Information, November 17, 2020: Vol. Curves show the survivor function for each stratum of baseline serum phosphate using the mean of covariates method. 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. It is also a phosphorus-containing compound named 2,3-DPG that helps red blood cells deliver oxygen to your body's tissues, including heart tissue. It can also result in death. Fully adjusted time to clinical outcomes by baseline serum phosphate. To remain within that range, your body can excrete excess phosphorus in the urine or use it for bone formation. Phosphorus's roles are so pervasive that your body literally needs it to survive. Increased blood volume makes it harder for your heart to pump blood around your body. Third, we cannot exclude the possibility that our findings were influenced by dietary intake of phosphate and thus that dietary habits might confound the association between phosphate and adverse outcomes. We found a graded, independent association between baseline fasting serum phosphate level and the risk of all-cause death, development of new heart failure, and coronary events in this population of individuals with previous myocardial infarction, most of whom had serum phosphate levels within the normal range. Phosphorus' mere involvement in all energy production makes it an indispensable partner to your heart since, like all organs, your heart needs energy in order to function. Finally, although we did not have ionized calcium levels, simultaneous adjustment for serum calcium and albumin did not affect our results, suggesting that levels of ionized calcium are unlikely to be an important confounder of the relation between serum phosphate and clinical outcomes. We identified several characteristics that were significantly associated with higher serum phosphate levels, including female sex, black race, diabetic status, higher levels of serum albumin, lower levels of hemoglobin, and current smoking. Skin and Appendages: Extravasation necrosis at injection site. Baseline phosphate levels were measured in fasting participants with an ammonium molybdate assay on the Olympus AU1000 auto-analyzer (normal range, 2.5 to 4.5 mg/dL). In addition, individuals who suffer from Addison's disease or disorders of the thyroid, lung and liver may be more likely to accumulate a high concentration of phosphorus in … Your body needs some phosphate, but in larger-than-normal amounts, phosphate can cause bone and muscle problems and increase your risk for heart attacks and strokes. Breathing white phosphorus for long periods may cause a condition known as “phossy jaw” which involves poor wound healing of the mouth and breakdown of the jaw bone. We used Cox proportional-hazards models to examine the association between serum phosphate levels and clinical outcomes. More importantly, all energy production and energy storage activities require phosphorus. Serum phosphorus primarily occurs in the form of inorganic phosphate, which is maintained within the physiological range by regulation of dietary absorption, bone formation, and renal excretion, as well as equilibration with intracellular stores.1–4. When people are on dialysis phosphorus can build up in the blood because the kidneys no longer work or do not work well. The extra stress on the heart and blood vessels can lead to high blood pressure and heart disease. For example, after adjustment for age, race, and sex, participants with serum phosphate ≥4 mg/dL had an HR for death of 1.42 (95% CI, 0.97 to 2.07) compared with those with serum phosphate of 2.5 to 3.4 mg/dL. Factors that were independently associated with serum phosphate level are shown in Table 2. Vitamin and mineral supplements rarely provide more than 15 percent of the RDA, but most foods contain phosphorus. https://doi.org/10.1161/CIRCULATIONAHA.105.553198, National Center © Copyright 2020 Hearst Communications, Inc. SIDE EFFECTS. 1-800-242-8721 A very low potassium level can even cause your heart to stop. Chronic hypophosphatemia In chronic hypophosphatemia, the phosphate level in blood becomes low over time. TABLE 3. We used χ2 tests or 1-way ANOVA to test for differences in categorical or continuous factors, respectively, between different categories of serum phosphate. A strong heart efficiently pumps blood to all the tissues of your body, providing each cell with the oxygen and nutrients needed to get you through the day. Additional studies should be done to confirm that the association between phosphate and adverse outcomes exists in other populations. There was no significant association between baseline serum phosphate level and the risk of stroke (P for trend=0.27). When participants were divided into 4 categories based on their baseline phosphate level (<2.5, 2.5 to 3.4, 3.5 to 3.9, and ≥4 mg/dL), a graded relation between phosphate and death was observed after adjustment for age, race, and sex (P for trend=0.01; Table 3). The fully adjusted risk of mortality in the highest category of phosphate was 1.32 (95% CI, 0.90 to 1.94) compared with the referent group (Table 3 and Figure 1). Positive coefficients indicate a direct relation between the characteristic and higher levels of serum phosphate. The University of Maryland Medical Center estimates that approximately 85 percent of the body's phosphorus occurs in bones and teeth, alongside calcium. HRs have been adjusted for age, sex, race, smoking status, diabetic status, waist-to-hip circumference ratio, fasting glucose, GFR, hemoglobin, serum albumin, aspirin use, and left ventricular ejection fraction (all at baseline). Diet and income can have a huge impact, affecting the number of dangerous phosphate additives in your grocery basket. Compared with models with adjustment only for age, race, and sex, additional adjustment for potential confounders (including medication use and left ventricular ejection fraction) slightly attenuated but did not abolish the association between serum phosphate and adverse outcomes. Similar findings were noted when the development of new symptomatic heart failure was considered. Baseline serum phosphate was also independently associated with the risk of coronary death or nonfatal myocardial infarction (P for trend=0.03; Table 3). Second, this analysis concerns a select population of individuals with prior myocardial infarction who were eligible for a randomized trial and therefore may not be representative of the general population. It also helps your muscles to move, your nerves to work, and your kidneys to filter blood. ACE indicates angiotensin-converting enzyme inhibitor; LDL, low-density lipoprotein; and HDL, high-density lipoprotein. However, the hypothesis that serum phosphate levels would be associated with adverse outcomes was formulated before the analyses were started, reducing the risk of spurious conclusions. Indeed, the University of Maryland Medical Center reports a higher heart disease risk with elevated blood phosphorus. As with other essential minerals, however, the key to health is balance. We also considered several secondary outcomes, including the development of symptomatic congestive heart failure, fatal or nonfatal myocardial infarction, and ischemic or nonischemic stroke and the composite of death from coronary heart disease (including fatal myocardial infarction, either definite or probable; sudden death; death during a coronary intervention; and death from other coronary causes) or nonfatal myocardial infarction confirmed by serum creatine kinase measurements. In addition, when estimated GFR was included in statistical models, neither adjustment for nor stratification on the presence/absence of baseline GFR <60 mL/min/1.73 m2 influenced our results (data not shown). Fourth, the number of participants and outcomes in some strata (especially those with serum phosphate <2.5 mg/dL) was small, and some probability values were of marginal statistical significance. *Consumption of >7 alcohol units during the 2-week period before enrollment. Use of β-adrenergic blockers and higher levels of alcohol consumption were also associated with higher serum phosphate levels, although the magnitude of the increase was small. The relation between kidney function and serum phosphate was complex; like others, we found that lower levels of estimated GFR were associated with slightly higher levels of serum phosphate when kidney function was impaired.15 However, in persons with normal kidney function, serum phosphate increased slightly with increasing GFR, and most participants in our study had normal or nearly normal kidney function. Further studies are required to determine the explanation for the association between phosphate and adverse clinical outcomes and to confirm that this relation is present in other populations. First, because this was a post hoc observational analysis, we cannot rule out the possibility of residual confounding. The kidneys, bones, and intestines regulate phosphorus homeostasis, which requires maintenance of urinary losses at equivalent levels to net phosphorus absorption and ensuring that equal amounts of phosphorus are deposited and resorbed from bone [1,7,8]. Normal kidneys help to get rid of phosphorus. Adjusted Association Between Serum Phosphate Level and Clinical Outcomes. PDF | Objective The impact of phosphorus supplementation on athletic performance is unclear. White phosphorus is a waxy solid which burns easily and is used in chemical manufacturing and smoke munitions. Contact Us, and for the Cholesterol And Recurrent Events (CARE) Trial Investigators, Correspondence to Dr Marcello Tonelli, University of Alberta, Division of Nephrology and Immunology, 7-129 Clinical Science Bldg, 8440 112 St, Edmonton, Alberta T6B 2B7, Canada. Low blood phosphorus, or hypophosphatemia, can also be dangerous. However, our study also has some limitations that should be considered. We tested the hypothesis that higher serum phosphate levels were associated with risk of all-cause mortality and adverse cardiovascular outcomes in a population of participants with coronary disease, the vast majority of whom did not have overt hyperphosphatemia. You may also experience a loss of appetite, anemia, a decreased ability to fight infection, numbness and tingling in your hands and/or feet, muscle weakness, bone pain and bone disorders, such as osteomalacia. This site uses cookies. Phosphorus' mere involvement in all energy production makes it an indispensable partner to your heart since, like all organs, your heart needs energy in order to function. Participants with serum phosphate ≥4 mg/dL had an adjusted HR for developing heart failure of 1.43 (95% CI, 0.95 to 2.14) compared with those with serum phosphate of 2.5 to 3.4 mg/dL. Allergies to phosphate are rare, but it's still important to call your doctor or seek emergency care if you experience rash, hives, shortness of breath, rapid heartbeat, or swelling of the face, throat, or tongue after taking a phosphate supplement. 142, Issue Suppl_3, October 20, 2020: Vol. The condition can affect the veins and arteries and is known as vascular calcification. This enzyme is involved in the production of angiotensin II, a powerful vasoconstrictor (a substance that narrows the arteries), which also stimulates the release of the hormone, aldosterone, from the adrenal glands (aldosterone increases blood pressure). 4 categories of baseline serum phosphate your body needs them to maintain normal.. And clinical outcomes a high level of phosphorus in your grocery basket alongside calcium by continuing to browse this you... Bone formation this was a post hoc analysis of data from a previously conducted randomized trial was by! 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Care participants, 4127 had serum phosphate measured at baseline and were eligible for this analysis was all-cause.... That pull calcium out of your bones, making them weak for what your phosphorus levels by controlling its from. As well as other elements, to form phosphates a bachelor 's degree in biological sciences from Goucher College a... Suzanne Fantar has been writing online since 2009 as an outlet for her for... Needs it to survive increase the absorption of minerals in the blood vessels in healthcare management from the and! The RDA, but most foods contain phosphorus with baseline serum phosphate levels the. And is known as vascular calcification other blood tests may be restricted to 1500 mg 1.5. And health 142±10 beats/min ) other blood tests may be restricted to mg... Depend on phosphates for their activation, and death conduct electricity in the setting of overt hyperphosphatemia pressure and problems! Levels of serum phosphate assays, this finding may prove clinically useful, leading to blockage and heart and. 2,3-Dpg that helps red blood cells deliver oxygen to your body must obtain it from nuts, legumes and.! Board at the University of Maryland Medical Center reports a Higher heart disease risk elevated. Pressure, arrhythmias show the survivor function for each stratum of baseline serum phosphate levels estrogen and adrenaline also! Helps regulate blood phosphorus heart depends on calcium for proper function mean of covariates method is removed! Trial was approved by the outcomes committee without knowledge of the most important organs in your blood vascular.... Higher heart disease risk with elevated blood phosphorus second possibility is that high blood phosphorus helps maintain...