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In which of the following groups has albuminuria
been demonstrated to increase cardiovascular and all-cause mortality
risk?
1. Unselected patients
2. Patients with diabetes
3. Patients with hypertension
4. Patients with other significant cardiovascular risk factors
5. All of the above
See this weeks item # 10
Albuminuria is a significant risk factor for increased cardiovascular
events and mortality. According to the current study, higher cardiovascular
and all-cause mortality risk is associated with albuminuria among unselected
patients, patients with diabetes and/or hypertension, and with other
significant cardiovascular risk factors. In a study by Gerstein and
colleagues, which appeared in the July 25, 2001, issue of JAMA, microalbuminuria
increased the relative risk of major cardiovascular events by a factor
of 1.83 and all-cause mortality by 2.09, with little difference between
patients with or without diabetes. The research demonstrated that for
every 0.4 mg/mmol increase in the albumin/creatinine ratio, the adjusted
hazard ratio of cardiovascular events increased by 5.9%.
In previously reported results of the LIFE study by Wachtell and colleagues,
LVH was associated with a higher relative risk of both micro- and macroalbuminuria
(relative risk = 1.6 and 2.6, respectively). The authors of that study,
which appeared in the March 2002 issue of the Journal of Hypertension,
follow up their research with the current study, designed to determine
the relative cardiac risk associated with both LVH and albuminuria.
Ann Intern Med. 2003;139:901-906
Study Highlights
All subjects were between 55 and 80 years of age and had hypertension
and LVH. They were randomized to receive either atenolol or losartan,
and the original study's primary objective was to determine the relative
efficacy of these two drugs in preventing cardiovascular morbidity and
mortality. The current research is derived from data from the same patient
cohort.
Patients were excluded if they had a history of myocardial infarction
or stroke within 6 months, congestive heart failure, or renal insufficiency.
Participants had a spot urine microalbumin test performed, and UACR
levels were calculated.
The primary outcome for this study was a composite of cardiovascular
death, stroke, and myocardial infarction. These end points were measured
across the continuum of albuminuria. All-cause mortality was also measured.
8,206 subjects (of 9,193 from the original study) were included in the
current analysis. Mean arterial blood pressure was 174/87 mm Hg, and
median UACR was 1.28 mg/mmol. Subjects were followed for a median of
4.8 years.
Overall rates of the various end points were 24.8 per 1,000 life-years
for the composite end point and 17.6 for all-cause mortality. After
adjusting for other risk factors, patients who did not give a urine
sample had an all-cause mortality that was 52% elevated above those
who gave a sample.
In the entire study cohort, for every 10-fold increase in UACR, the
hazard ratio for the composite end point increased by 54.9%. Risk of
cardiovascular mortality and all-cause mortality increased by 84.5%
and 66.4%, respectively. Stroke and myocardial infarction increased
by 49.3% and 41.0%, respectively.
In the sample of diabetic subjects, albuminuria levels were higher than
in the general study cohort (3.05 vs. 1.16 mg/mmol). However, the overall
risk of study end points in diabetic patients with albuminuria was lower.
For every 10-fold increase in UACR in the diabetic patients, the hazard
ratio for the composite end point increased by 39%. Risk of cardiovascular
mortality and all-cause mortality increased by 46.9% and 38.3%, respectively.
Incidence of stroke and myocardial infarction increased by 37.3% and
20.0%, respectively.
In nondiabetic patients, the risk of the composite end point was elevated
at a UACR level of 1.16 mg/mmol or greater. This level is lower than
most common definitions of albuminuria.
Risk of poor outcomes increased progressively as UACR increased, suggesting
a linear relationship between albuminuria and cardiovascular morbidity
and mortality.
This study was limited as an analysis of research that was originally
designed with different goals in mind. Also, UACR was determined from
a single spot urine sample.
Pearls for Practice
Albuminuria is associated with increased cardiovascular risk across
different patient populations.
The presence of albuminuria in patients with hypertension should prompt
more aggressive treatment to reduce cardiovascular risk.
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