Blood levels of electrolytes (salts like sodium or chloride) are normally maintained within very narrow limits by a variety of mechanisms in the body. These salts are part of a standard panel of blood tests performed during medical assessment by doctors. Very high or very low levels of these salts in the blood are indicators of serious disease and require immediate treatment. However, there is evidence that minor changes in the blood levels of these salts (i.e. within the range considered normal) are markers of cardiovascular diseases like heart attacks and stroke. Thus if these tests can be used to identify those individuals at high risk of developing heart attack or stroke in the future, then this can be used for starting early preventive measures without performing additional expensive tests. Moreover, conducting a detailed study of these salts will enable us to have a deeper understanding of the possible mechanisms that is indicated by these tests and will help us discover new treatments. To do this, we propose to examine the relationship between these blood tests and the risk of developing or dying from a range of cardiovascular diseases in health records from primary and hospital care.
The electrolytes in serum and urine (sodium (Na+), potassium (K+), bicarbonate, (HCO3), chloride (Cl-) and calcium (Ca2+) as well as the important renal biomarkers (urea, creatinine, phosphate, urate and microalbumin) play an integral role in intermediary metabolism and cellular function. Imbalances in the intra- and extracellular concentrations of each electrolyte are associated with adverse metabolic and physiological consequences. Under normal conditions homeostasis is maintained between intake, intra/extracellular shifts and excretion. In most cases depletion or repletion of electrolytes occur in tandem, requiring consideration of related cation/anion biomarker species (e.g. Na+ and K+). Electrolyte anomalies are commonly described in hospitalized patients and are associated with increased morbidity and mortality. There are few studies however examining electrolyte anomalies in non-acute populations such as the ones encountered in primary care. The objective of this study is to examine separately, for independence, the relationship between the first recorded measurement of each biomarker and the incidence of various diagnosed CVD events and cause-specific mortality. For this longitudinal cohort of men and women aged 18 and older, we will employ risk prediction models, clustered by practice to determine the associations. Models will be validated for their discrimination, calibration and overall fit using a panel of sensitivity analyses.
1. All-cause mortality (identified through ONS data)
2. Fatal and non-fatal CVD outcomes:
a. Stable angina (identified from CPRD diagnoses, prescription of nitrates or from HES diagnoses)
b. Unstable angina (identified from CPRD/HES diagnoses)
c. Coronary artery disease not further specified (identified from CPRD/HES diagnoses)
d. Acute myocardial Infarction (identified from CPRD/HES diagnoses)
e. Unheralded coronary death (identified from ONS data)
f. Heart failure (identified from CPRD/HES diagnoses)
g. Ventricular arrhythmia (identified from CPRD/HES diagnoses)
h. Atrial fibrillation (identified from CPRD/HES diagnoses)
i. Sudden cardiac death (identified from ONS data)
j. Transient ischaemic attack (identified from CPRD/HES diagnoses)
k. Ischaemic stroke (identified from CPRD/HES diagnoses)
l. Stroke not further specified (identified from CPRD/HES diagnoses)
m. Subarachnoid haemorrhage (identified from CPRD/HES diagnoses)
n. Intracerebral haemorrhage (identified from CPRD/HES diagnoses)
o. Peripheral arterial disease (identified from CPRD/HES diagnoses)
p. Abdominal aortic aneurism (identified from CPRD/HES diagnoses)
Sandosh Padmanabhan - Chief Investigator - University of Glasgow
Sandosh Padmanabhan - Corresponding Applicant - University of Glasgow
Alireza Moayyeri - Collaborator - UCB Celltech
Harry Hemingway - Collaborator - University College London ( UCL )
Linsay McCallum - Collaborator - University of Glasgow
Michail Katsoulis - Collaborator - Farr Institute of Health Informatics Research
Simon G Anderson - Collaborator - University of Manchester
Spiros Denaxas - Collaborator - University College London ( UCL )
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Townsend Score