We reviewed the evidence linking mild
renal insufficiency (MRI) to an increased cardiovascular risk. A number of cardiovascular risk factors become prevalent with MRI, including night-time
hypertension, increase in
lipoprotein(a), in
homocysteine, in asymmetric dimethyl-
arginine (ADMA), markers and
mediators of inflammation, and
insulin resistance. Also, an epidemiologic association between
coronary artery disease and
nephrosclerosis, a frequent cause of mild
renal insufficiency in the elderly, is documented. In the middle-aged, general population MRI, found in 8% of women and 9% of men, was not associated with
cardiovascular disease. However, in a representative sample of middle-aged British men, the risk of
stroke was 60% higher for the subgroup of people with MRI; in people at high cardiovascular risk (mostly
coronary disease), the HOPE study found a 2-fold (unadjusted), or 1.4-fold (adjusted), higher incidence of cardiovascular outcomes with MRI. The incidence of primary outcome increased with the level of serum
creatinine. Several studies determined the cardiovascular risk associated with MRI in
hypertension. In HDFP, as in HOPE, cardiovascular mortality increased with higher serum
creatinine (five-fold difference in cardiovascular mortality between the lowest and the highest
creatinine strata). The risk associated with
renal insufficiency was independent from other classic cardiovascular risk factors. In hypertensives with low risk, the HOT, and a small Italian trial found about a doubling in cardiovascular outcomes in MRI. However, in MRFIT, increase in follow-up
creatinine predicted future
cardiovascular disease, not baseline
creatinine. These observational data suggest that MRI, independent of etiology, is a strong predictor of
cardiovascular disease, present in 10% of a population at low risk, and up to 30% at high cardiovascular risk. No prospective therapeutic trials, aimed at reducing the cardiovascular burden in people with MRI, are available. Subgroup analyses of the HOPE study indicate that ACE inhibition with
ramipril is beneficial without an increased risk for side effects like
acute renal failure or
hyperkalemia. Thus, the frequent practice of withholding
ACE inhibitors from patients with mild
renal insufficiency is unwarranted, especially since this identifies a group at high risk that appears to benefit most from treatment. In addition, there is evidence that
ACE inhibitors improve renal outcomes in
renal insufficiency. Prospective studies should test the predictive power of MRI for
cardiovascular disease and therapeutic options.