Serum phosphate levels and the risk of cardiovascular disease and metabolic syndrome: A double-edged sword

Park, Wan; Kim, Bum Soo; Lee, Jae Eun; Huh, Jung Kwon; Kim, Byung Jin; Sung, Ki Chul; Kang, Jin Ho; Lee, Man Ho; Park, Jung Roe; Oh, Ki Won; Lee, Won Young; Park, Cheol‐Young; Park, Sung Woo; Kim, Sun Woo

doi:10.1016/j.diabres.2008.08.018

Cited by 67 publications

(65 citation statements)

References 21 publications

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“…Indeed, high phosphate was associated with a more favorable CVD risk profile, including lower blood pressure and high-density lipoprotein-cholesterol, which has been noted in other studies, 29,30 and no association was seen with markers of coagulation (D-dimer) or endothelial dysfunction (vWF). However, a weak positive association was seen with inflammation and phosphate related positively to N-terminal prohormone of brain natriuretic peptide, a marker of cardiac function.…”

Section: Serum Phosphate and Cvdmentioning

confidence: 81%

Alkaline Phosphatase, Serum Phosphate, and Incident Cardiovascular Disease and Total Mortality in Older Men

Wannamethee

Sattar

Papcosta

et al. 2013

ATVB

107

120

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Objective-We have examined the association between serum phosphate and alkaline phosphatase (ALP) with incident cardiovascular disease (CVD) outcomes and total mortality in older men. Approach and Results-A prospective study of 3381 men, aged 60 to 79 years, without a history of myocardial infarction or stroke followed up for an average 11 years during which there were 605 major CVD events (fatal coronary heart disease and nonfatal myocardial infarction, stroke, and CVD death) and 984 total deaths. ALP but not serum phosphate was associated with increased risk of coronary heart disease and overall CVD events which persisted after adjustment for CVD risk factors and markers of inflammation and after exclusion of men with chronic kidney disease (adjusted hazard ratio per SD, Both raised phosphate and ALP were associated with significantly increased total mortality after full adjustment and exclusion of men with chronic kidney disease. Conclusions-ALP but not serum phosphate is associated with coronary heart disease risk in elderly men. High levels of ALP and serum phosphate are both associated with increased total mortality.

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Section: Serum Phosphate and Cvdmentioning

confidence: 81%

Alkaline Phosphatase, Serum Phosphate, and Incident Cardiovascular Disease and Total Mortality in Older Men

Wannamethee

Sattar

Papcosta

et al. 2013

ATVB

107

120

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“…Although there are reports for increased mortality with high levels of serum phosphate, low levels of phosphate are also associated with malnutrition, low physical activity, hypertension, and metabolic syndrome. 3,9 Racial differences and genetic polymorphisms among Western and Asian individuals might be present. 5 Compared with Asian diets, Western diets are relatively high in bioavailable phosphate.…”

Section: Discussionmentioning

confidence: 99%

Serum Alkaline Phosphatase and Phosphate in Cerebral Atherosclerosis and Functional Outcomes After Cerebral Infarction

Kim

Song

et al. 2013

Stroke

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ResultsOf the 1043 patients, 62.51% were men, and their mean age was 65.82±12.79 years. Mean values were 62.45±19.61 U/L for ALP and 1.07±0.21 mmol/L for phosphate. Clinical characteristics and their associations with ALP/phosphate are Background and Purpose-Higher serum alkaline phosphatase (ALP) and phosphate levels are associated with atherosclerotic disease and an increased risk of cardiovascular events. However, the association of ALP/phosphate with cerebral atherosclerosis and prognosis in patients with acute stroke is not well known. Methods-In 1034 patients with first-ever acute cerebral infarction, levels of ALP and phosphate were compared with (1) cerebral atherosclerosis and (2) poor long-term functional outcomes as defined by the modified Rankin Scale >2 at 3 months after stroke onset. Results-ALP levels were not associated with cerebral atherosclerosis. However, higher levels of ALP were associated with a poor functional outcome (adjusted odds ratio per 1 SD, 1.25; 95% confidence interval, 1.04-1.50). Phosphate was associated with neither cerebral atherosclerosis nor functional outcome. Conclusions-A higher level of ALP was not associated with cerebral atherosclerosis but was an independent prognostic factor for long-term functional outcome after acute cerebral infarction. shown in Tables I and II in the online-only Data Supplement. ALP was associated with old age, higher frequency of hypercholesterolemia, and higher hemoglobin, cholesterol, alanine aminotransferase, and glucose. Phosphate was associated with female sex, lower National Institutes of Health Stroke Scale score at admission, higher cholesterol, triglyceride, and calcium, and lower hemoglobin and high-sensitivity C-reactive protein.There were 623 patients (59.73%) with cerebral atherosclerosis. The levels of ALP/phosphate were not associated with intracranial or extracranial cerebral atherosclerosis (Table 1). When we subdivided patients according to the degree of cerebral atherosclerosis (no atherosclerosis, <50%, 50%-75%, and ≥75% or occlusion), there was no significant difference of ALP/phosphate among them (Table III in Table 2). Penalized-spline curve demonstrated a positive relationship between levels of ALP and an increased risk for poor functional outcomes (Figure). DiscussionIn this study, we tested the hypothesis that elevated ALP/ phosphate levels are associated with cerebral atherosclerosis, which was based on previous reports that showed a higher prevalence of coronary artery disease and peripheral artery disease in patients with elevated ALP/phosphate levels. However, such a relationship between serum ALP/phosphate levels and cerebral atherosclerosis was not found in our study. The action of ALP/phosphate might differ in each vascular bed. Susceptibility to atherosclerosis is strongly influenced by intrinsic differences in the cells composing each vascular system.6 Associated risk factors and pathological findings, including calcification, differ according to the location of the atherosclerosis. Although we defined atheros...

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“…Excess P i has been independently associated with cardiovascular morbidity and mortality (1, 7). On the other hand, metabolic syndrome represents an important cluster of risk factors for the development of cardiovascular disease (32, 48), and it was proposed recently that disturbances in P i metabolism may be a key feature of metabolic syndrome, since both too high and too low serum P i levels have been correlated with cardiovascular risk factors and elements of metabolic syndrome (19,23,40). It may be important to maintain an appropriate serum level of P i for the prevention of cardiac disease and metabolic syndrome.…”

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confidence: 99%

Effects of dietary phosphate on glucose and lipid metabolism

Abuduli

Ohminami

Otani

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Recent epidemiological and animal studies have suggested that excess intake of phosphate (Pi) is a risk factor for the progression of chronic kidney disease and its cardiovascular complications. However, little is known about the impact of dietary high Pi intake on the development of metabolic disorders such as obesity and type 2 diabetes. In this study, we investigated the effects of dietary Pi on glucose and lipid metabolism in healthy rats. Male 8-wk-old Sprague-Dawley rats were divided into three groups and given experimental diets containing varying amounts of Pi, i.e., 0.2 [low Pi (LP)], 0.6 [control Pi (CP)], and 1.2% [high Pi (HP)]. After 4 wk, the HP group showed lower visceral fat accumulation compared with other groups, accompanied by a low respiratory exchange ratio (V CO2/V O2) without alteration of locomotive activity. The HP group had lower levels of plasma insulin and nonesterified fatty acids. In addition, the HP group also showed suppressed expression of hepatic lipogenic genes, including sterol regulatory element-binding protein-1c, fatty acid synthase, and acetyl-CoA carboxylase, whereas there was no difference in hepatic fat oxidation among the groups. On the other hand, uncoupling protein (UCP) 1 and peroxisome proliferator-activated receptor-␥ coactivator-1␣ (PGC-1␣) expression were significantly increased in the brown adipose tissue (BAT) of the HP group. Our data demonstrated that a high-Pi diet can negatively regulate lipid synthesis in the liver and increase mRNA expression related to lipid oxidation and UCP1 in BAT, thereby preventing visceral fat accumulation. Thus, dietary P i is a novel metabolic regulator. dietary phosphate; energy metabolism; brown adipose tissue; visceral fat OBESITY CONTINUES TO BE A MAJOR PUBLIC HEALTH PROBLEM worldwide. Overnutrition and an increased consumption of fast foods are primary factors contributing to this problem. Fast foods or processed foods have high energy density and also frequently contain a large amount of P i as a food additive. Recent epidemiological studies have suggested that a high dietary P i intake can be associated with increased cardiovascular risk and other metabolic disorders.P i is an essential nutrient that significantly affects skeletal formation, energy metabolism, and intracellular signaling (43,45). P i homeostasis is regulated by the absorption of P i in the intestine, bone formation/resorption, and reabsorption of P i in the kidney. The kidney is particularly important in the regulation of P i homeostasis (36, 45). Most P i -regulating factors, such as high/low P i intake, 1,25-dihydroxyvitamin D [1,25(OH) 2 D], parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), can regulate P i reabsorption in the kidney to maintain the P i homeostasis (6, 36, 43).Recent epidemiological and animal studies have suggested that an excessive intake of P i is a risk factor for the progression of chronic kidney disease and the occurrence of cardiovascular complications (8, 45). Excess P i has been independently associated with ...

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Serum phosphate levels and the risk of cardiovascular disease and metabolic syndrome: A double-edged sword

Cited by 67 publications

References 21 publications

Alkaline Phosphatase, Serum Phosphate, and Incident Cardiovascular Disease and Total Mortality in Older Men

Alkaline Phosphatase, Serum Phosphate, and Incident Cardiovascular Disease and Total Mortality in Older Men

Serum Alkaline Phosphatase and Phosphate in Cerebral Atherosclerosis and Functional Outcomes After Cerebral Infarction

Effects of dietary phosphate on glucose and lipid metabolism

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