ratio (ACR), in a population without excretory kidney impairment (). However, since higher serum phosphate concentration is itself associated with lower urine creatinine excretion (), this association might not actually reflect a difference in albumin leak. A reduction in 24h urine phosphate, considered a reflection of lower dietary phosphate intake, was an independent predictor of albuminuria reduction in the PREMIER study of lifestyle interventions in obese subjects with preserved kidney function (though this study did not report serum phosphate data)(). Lower 25(OH)D concentrations have been associated with higher ACR (), but this may reflect confounding by muscle mass as the determinant of creatinine excretion rate; as might be expected, lower 25(OH)D is associated with sarcopaenia (). Whether higher-normal PTH and FGF-23 are associated with higher urine albumin excretion has not been reported. Summary of evidence and unanswered questions In summary, in general population samples without recognised metabolic bone pathology, variations in bone mineral axis parameters predict substantial increases in CVD and mortality. Although some bone mineral parameters are associated with traditional cardiovascular risk factors, adjusting for traditional risk factors does not abolish the prediction of adverse cardiovascular outcomes; higher phosphate predicts cardiovascular events despite being inversely associated with likelihood of metabolic syndrome components. Plausible pathophysiological mechanisms involving endothelium and other cardiovascular tissues have been proposed, but causal relationships have not been proven to underlie the clinical observations. If causal relationships exist this would have public health implications for cardiovascular disease prevention. The important unanswered questions in this field are therefore: Do the observed associations between bone mineral axis parameters and CVD reflect pathological effects of bone mineral axis disturbance? What is the most important parameter to optimise and how should this be done? What are the mechanisms by which bone mineral axis disturbance causes cardiovascular disease? How do these pathways interact with traditional paradigms of cardiovascular disease pathogenesis?
ratio (ACR), in a population without excretory kidney impairment (). However, since higher serum phosphate concentration is itself associated with lower urine creatinine excretion (), this association might not actually reflect a difference in albumin leak. A reduction in 24h urine phosphate, considered a reflection of lower dietary phosphate intake, was an independent predictor of albuminuria reduction in the PREMIER study of lifestyle interventions in obese subjects with preserved kidney function (though this study did not report serum phosphate data)(). Lower 25(OH)D concentrations have been associated with higher ACR (), but this may reflect confounding by muscle mass as the determinant of creatinine excretion rate; as might be expected, lower 25(OH)D is associated with sarcopaenia (). Whether higher-normal PTH and FGF-23 are associated with higher urine albumin excretion has not been reported. Summary of evidence and unanswered questions In summary, in general population samples without recognised metabolic bone pathology, variations in bone mineral axis parameters predict substantial increases in CVD and mortality. Although some bone mineral parameters are associated with traditional cardiovascular risk factors, adjusting for traditional risk factors does not abolish the prediction of adverse cardiovascular outcomes; higher phosphate predicts cardiovascular events despite being inversely associated with likelihood of metabolic syndrome components. Plausible pathophysiological mechanisms involving endothelium and other cardiovascular tissues have been proposed, but causal relationships have not been proven to underlie the clinical observations. If causal relationships exist this would have public health implications for cardiovascular disease prevention. The important unanswered questions in this field are therefore: Do the observed associations between bone mineral axis parameters and CVD reflect pathological effects of bone mineral axis disturbance? What is the most important parameter to optimise and how should this be done? What are the mechanisms by which bone mineral axis disturbance causes cardiovascular disease? How do these pathways interact with traditional paradigms of cardiovascular disease pathogenesis?
Corrected%20Thesis.docx