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U-shaped relationship between serum phosphate and cardiovascular risk: A retrospective cohort study.

ABSTRACT: High serum phosphate is associated with coronary artery disease in patients with normal and impaired renal function. We asked: Does the serum phosphate range provide prediction of primary cardiac events? We extracted coded primary care data for over 100,000 patients from a database of 135 primary medical practices. Patients aged between 18 and 90 years without pre-existing cardiovascular diagnoses were included from a potential sample of over 1·2 million individuals.Binary logistic regression models were used to evaluate the contribution of QRISK factors and electrolytes, including serum phosphate, to cardiac outcomes at five and nine years following an initial phosphate measurement. At five-year review (n = 113,993), low serum phosphate (OR 1·75, 95%CI 1·36-2·23, p<0·001), high-normal (OR 1·50, 95%CI 1·29-1·74, p<0·001), and high serum phosphate (OR 1·74, 95%CI 1·06-2·70, p = 0·02) were long-term risk factors for primary cardiac disease events after adjusting for confounding variables. A similar pattern was seen at our nine-year review.The extremes of serum phosphate may confer cardiac event risk with a U-shaped trend. In particular, we raise new cardiac concerns for low serum phosphate in the general population. Also, the normal range for phosphate may require redefinition among healthy adults.

SUBMITTER: Hayward N

PROVIDER: S-EPMC5695582 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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U-shaped relationship between serum phosphate and cardiovascular risk: A retrospective cohort study.

Hayward Nicholas N McGovern Andrew A de Lusignan Simon S Cole Nicholas N Hinton William W Jones Simon S

PloS one 20171108 11

<h4>Background</h4>High serum phosphate is associated with coronary artery disease in patients with normal and impaired renal function. We asked: Does the serum phosphate range provide prediction of primary cardiac events? We extracted coded primary care data for over 100,000 patients from a database of 135 primary medical practices. Patients aged between 18 and 90 years without pre-existing cardiovascular diagnoses were included from a potential sample of over 1·2 million individuals.<h4>Method ...[more]

PMID: 29117214

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Project description:ObjectivesThis research aims to explore the impact of serum phosphate on the mortality of critically ill patients.DesignA retrospective large cohort study.SettingOur data were extracted from a publicly accessible database named 'Multiparameter Intelligent Monitoring in Intensive Care Database III'.Participants27 131 patients were included by clear definitions of selection and exclusion criteria.InterventionsWe used initial phosphate at admission as a design variable. Patients were divided into six groups with different serum phosphate levels and five groups at different intensive care unit (ICU) departments.Primary and secondary outcomes28-day and 90-day mortality were primary outcomes. All-cause mortality and length of stay ICU were secondary outcomes.ResultsPatients with very-high-normal serum phosphate, hypophosphataemia and hyperphosphataemia had worse outcomes. And the relationship between serum phosphate and the probability of 28-day or 90-day mortality had a linear relationship. After adjustment for potential confounders, hypophosphataemia and hyperphosphataemia were not significantly associated with 28-day or 90-day mortality. Nevertheless, at the medical ICU, hyperphosphataemia was associated with increased 28-day or 90-day mortality (HR=0.64, 95% CI 0.48 to 0.84, p=0.0017; HR=0.72, 95% CI 0.57 to 0.91, p=0.0067, respectively), using group 2 (≥2.5 mg/dL and <3.0 mg/dL) as the reference group.ConclusionsPatients with very-high-normal serum phosphate also had worse outcomes, it might be necessary to re-evaluate the definitions of the normal reference range for serum phosphate. Hypophosphataemia and hyperphosphataemia are not the independent risk factors of 28-day or 90-day ICU mortality, which leads us to consider whether phosphate monitoring is not a necessary measure in critically ill patients. But hyperphosphataemia was associated with increased 28-day or 90-day mortality at the medical ICU, which emphasises the potential importance of early diagnosis and treatment of hyperphosphataemia for the patients who were admitted to the medical ICU.

Project description:ObjectiveTo evaluate the associations between serum uric acid (SUA) levels and cardiovascular disease (CVD) risk factors, focusing on potential sex-specific differences.DesignA retrospective cohort study.SettingA large community-based survey was conducted every two years from 2010 to 2018 in Hangzhou, Zhejiang Province, outheastern China.Participants6119 participants aged 40 years and above who underwent at least three times of physical examinations were enrolled.MethodsParticipants were categorised into four groups (Q1-Q4) based on baseline SUA quartiles within the normal range, with hyperuricaemia (HUA) as the fifth group. The Q1 was the reference. By stratifying participants by gender, the relationships between SUA levels and systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG) and total cholesterol (TC) were investigated using linear regression models in the generalised estimating equation. Additionally, the associations of elevated SUA levels and HUA with hypertension, hyperglycaemia and dyslipidaemia were correspondingly examined using multivariate logistic regression models.ResultsAfter adjusting for confounding variables, we found positive associations between SUA levels and SBP, DBP, FBG and TC in women, and with TC in men (p<0.01). Likewise, elevated SUA quartiles and HUA were linked to increased dyslipidaemia risk in both sexes, and increased hyperglycaemia risk only in women, with HRs (95% CI) of 1.64 (1.05 to 2.55) and 2.37 (1.47 to 3.81) in the Q4 and HUA group, respectively. Women with HUA had higher hypertension risk (HR=1.45, 95% CI 1.21 to 1.73), while no such association was observed in men. Stratified analyses revealed significant associations between elevated SUA levels and CVD risk factors in postmenopausal and non-obese women.ConclusionsElevated SUA levels increase the risk of dyslipidaemia in both sexes. SUA levels within normal range and HUA are positively associated with hyperglycaemia and hypertension in postmenopausal women, but not in men.

Project description:BackgroundConcentrations of serum 25-hydroxyvitamin D [25(OH)D] below 20 ng/mL and above 50 ng/mL have been associated with chronic adverse events including cardiovascular disease.ObjectiveTo conduct a comprehensive population-based study in the United States of the relationship of low and high serum 25(OH)D levels with cardiovascular disease.MethodsWe identified all serum 25(OH)D measurements in adults age 18 years and older residing in Olmsted County, MN between January 1, 2005 and December 31, 2011, using the resources of the Rochester Epidemiology Project. Any new diagnosis of cardiovascular disease was the primary outcome, and time zero was 30 days after first 25(OH)D measurement. Patients were followed until their last clinical visit as an Olmsted County resident, December 31, 2014, or death. Categories of 25(OH)D values were examined using predetermined ranges of interest: <12, 12-19, 20-50 (reference range), and >50 ng/mL. Multivariable Cox proportional hazards models were adjusted for age, BMI, sex, race, smoking history, season of 25(OH)D measurement, hypertension, hyperlipidemia, socioeconomic status and Charlson comorbidity index at time of 25(OH)D measurement.ResultsA total of 11,002 unique persons had a 25(OH)D measurement, with a mean (±SD) value of 30.0 ± 12.9 ng/mL. Mean age was 54.3 ± 17.2 years, and the majority were female (77.1 %) and white (87.6 %). There were 4124 new diagnoses of cardiovascular disease in this cohort after a median overall follow-up of 4.8 years (IQR 3.4-6.2). Adjusted cardiovascular disease hazard ratios (HRs) (95 % confidence interval) for 25(OH)D values <12, 12-19, and >50 ng/mL, compared to the reference range 20-50 ng/mL, were 1.28 (1.12-1.46), 1.19 (1.09-1.31), and 1.10 (0.95-1.26), respectively.ConclusionValues of 25(OH)D <20 ng/mL were associated with development of a new diagnosis of cardiovascular disease. There was no significant association between 25(OH)D values >50 ng/mL and cardiovascular disease.

Project description:Introduction: MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development.<br><br>Methods: A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n=29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n=35) consisted of a random sample of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. miRNA profiling was performed using formalin-fixed, paraffin-embedded tumors. Biomarkers related to metastatic potential were identified independent of clinical stage, and a cutoff point was selected based on the optimal sensitivity and specificity (ROC curve). Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential. <br><br>Results: miRNA expression profiling identified several miRNAs that were either specific and shared across all clinical stages (p?0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family), cell proliferation and invasion (hsa-miR-16 and has-miR-205) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were up-regulated in metastatic cases of CSI and II. Furthermore, the combination of the 3 miRNAs identified for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs. <br><br>Conclusions: Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis. These miRNAs therefore represent new risk biomarkers of breast cancer metastasis and may be useful for future targeted therapies.

Project description:Background: Previous studies have demonstrated an association between hyperuricemia and cardiovascular disease (CVD). The Framingham study confirmed that patients with high atherosclerotic risks (HARs) had worse prognoses. However, after adjusting for confounding factors, the association between serum uric acid (SUA) and all-cause mortality and cardiovascular mortality remains unclear, especially for HAR patients. Objective: The aim of this study was to reveal the relationship of SUA with all-cause and cardiovascular mortality in HAR patients. Methods: This multicenter cohort study enrolled 3,047 participants, and the follow-up was 68.85 ± 11.37 months. Factors related to cardiovascular and all-cause mortality were tested by multivariate Cox regression analysis. Restricted cubic splines (RCSs) with knots were used to explore the shape of the dose-response relationship with SUA and the hazard ratio (HR) of all-cause and CVD mortality. SUA transformed by RCS was added to the Cox regression model as an independent variable, and all-cause and CVD mortality scores were calculated. Survival receiver operating characteristic curves were produced using a regression model predicting the score. Results: SUA demonstrated a "U-shaped" relationship with all-cause and cardiovascular mortality. SUA predicted all-cause and CVD mortality, with cutoff values of values of >370.5 μmol/L for males and >327.65 μmol/L for females and <180.5 μmol/L for males and <165.7 μmol/L for females, respectively. The survival ROC curve indicated that SUA is able to predict all-cause and CVD mortality, with areas under the curve of 0.702 and 0.711, respectively. The HRs of all-cause mortality (male and female) with hyperuricemia and hypouricemia were 2.08 and 2.01 and 2.04 and 1.98, respectively, and the HRs of CVD mortality (male and female) were 2.09 and 1.79, and 2.02 and 1.89, respectively. Conclusion: Abnormal SUA levels were significant and independent risk factors for all-cause and CVD mortality. Hyperuricemia and hypouricemia increased mortality in both males and females. Routine SUA evaluation and intensive management are needed for HAR patients. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03616769.

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U-shaped relationship between serum phosphate and cardiovascular risk: A retrospective cohort study.

Publications

U-shaped relationship between serum phosphate and cardiovascular risk: A retrospective cohort study.

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