Microalbuminuria: a valid marker for cardiovascular disease

Microalbuminuria is a term used to describe a small amount of the protein albumin in the urine, and not, as is sometimes mistaken, a small type of albumin. Advanced age — together with male gender, smoking, diabetes mellitus, hypertension and dyslipidaemia — have long been recognised as the classic predictors of cardiovascular disease (CVD)¹. Yet, as recent international data show, these risk factors alone do not sufficiently explain interpopulation variations in morbidity and mortality.²

This discovery has prompted researchers to investigate additional CVD markers, and there is now increasing evidence to suggest that the presence of small amounts of urinary albumin (microalbuminuria) may independently predict type 2 diabetes and/or hypertension.

This relationship has also been demonstrated in studies in older patients, where it has been shown that older patients with microalbuminuria have an increased CV risk. Microalbuminuria is characterised by a raised albumin excretion rate of between 20 and 200µg/min (30–300mg in a 24-hour period).³

A urinary albumin level above this upper threshold is defined as macroalbuminuria.⁴ Urinary albuminto-creatinine ratio measurements are also sometimes used to confirm diagnosis: a ratio between 30–300 (using mg of albumin and g of creatinine) or three–30 (using mg of albumin and mmol of creatinine) will usually verify microalbuminuric status.³ However, it is important to note that the creatinine level can be affected by exercise and gender. The albumin level may also fluctuate due to certain conditions.

Factors that can increase urinary albumin concentrations include: urinary tract infection, congestive heart failure, exercise, fever, poor glycaemic control and vaginal discharge^5-7 Therefore, since the amount of albumin and/or creatinine can vary, it is required that two out of three samples taken within one month are positive to confirm a diagnosis of microalbuminuria. Diagnosis with standard dipstick urinalysis can lead to some inaccuracies.

For this reason laboratory based albumin creatinine ratios (ACRs) are the preferred prognostic tool. Additionally, concentrations of albumin and creatinine in the initial, morning, midstream sample correlate very well with 24-hour measurements, and it may not be necessary to request repeated samples throughout the day or take a 24-hour urine sample6 . Multivariate analyses have revealed that microalbuminuria is strongly associated with increased age, hyperglycaemia, hypertension, smoking, non-Caucasian ethnicity and markers of inflammation such as C-reactive protein and raised lymphocytes.^1,5

Pathophysiological studies investigating the link between microalbuminuria and macrovascular disease have suggested that these inflammatory markers are the principal aetiological mediators.¹ Other hypotheses have proposed that albuminuria indicates an underlying endothelial dysfunction of the glomerular arteries, capillaries and/or intracellular matrix.^1,5

CV risk and microalbuminuria

Microalbuminuria affects around 11 per cent of people over the age of 40 years and may have significant consequences on long-term health.⁸ A prospective, population-based, six-year study of over 20,000 UK individuals aged between 40–79 years has shown that the presence of microalbuminuria significantly increases the risk of CV and all-cause mortality, and may be a useful marker for identifying older patients at the greatest absolute risk of fatal CV events10. The investigators found that compared to patients with normal albumin levels in their urine, microalbuminuria increased the likelihood of death by 48 per cent.

RAAS blockage has been shown. For example, in the REIN study the decline in GFR per month was significantly lower in the ramipril group than the placebo group (p=0.03), independent of baseline and follow-up arterial blood pressure.¹⁵ In addition the IDNT trial, investigating 1,715 patients with hypertension and nephropathy due to type 2 diabetes, showed that the serum creatinine concentration in the irbesartan group increased 21 per cent more slowly than in the amlodipine group, with no significant difference in blood pressure levels.¹⁶

Conclusion

In an effort to identify those at increased CV risk, microalbuminuria is becoming a more recognised marker of both renal and cardiovascular complications. Identifying older patients at risk of CV events is of great importance and the addition of a further tool to help risk stratify the elderly represents a marked improvement. In addition, subsequent RAAS intervention in these patients has been shown to reduce both blood pressure and the level of urinary albumin excretion, greatly improving their CV risk profile.

Dr Paul Newman is GP trainer at the Waverly Park Medical Practice in Glasgow

Conflict of interest: Dr Newman has been a consultant to, and received honoraria and travel grants from, numerous companies in the pharmaceutical industry that market cardiovascular and diabetes therapies.

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Dr Paul Newman

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