Measurement of circulating concentrations
of B-type natriuretic peptide or
N-terminal pro–B-type natriuretic peptide
(NT-proBNP) and high-sensitivity
troponin assays improve the prediction
of cardiovascular disease (CVD) in general
populations (1–3). Recent data from the
Action in Diabetes and Vascular Disease:
Preterax and Diamicron Modified Release
Controlled Evaluation (ADVANCE)
trial of intensive glucose control and
blood pressure lowering also show that
NT-proBNP and high-sensitivity troponin
T (hsTnT) improve CVD risk prediction in
those with type 2 diabetes (4). Microvascular
diseases also cause significant
morbidity in patients with diabetes; for
instance, diabetic nephropathy is a leading
cause of end-stage renal disease (5).
Clinical risk scores to predict the microvascular
complications of diabetes are
not in routine use but may be valuable
to help clinicians determine which patients
are at highest risk and to aid trial
design.
Clearly, there is some interrelationship
between increased microvascular and
macrovascular risk (6).Therefore, putative
microvascular risk scores might be
expected to contain some macrovascular
risk factors, as has been recently demonstrated
(7). However, the mechanisms
underlying elevation in risk of bothmicrovascular
and macrovascular risk are not
clear. Microvascular disease in the myocardium
might be a major cause of cardiac
morbidity among people with type 2
diabetes (8,9), and such subtle changes in
cardiac function (e.g., arising from subclinical
ischemia) might often precede
frank clinically detectable peripheral microvascular
disease. Indeed, elevated natriuretic
peptides in acute coronary
syndromesmay be correlated with abnormal
perfusion in patients undergoing angioplasty
(10). Further, cross-sectional
data in people with diabetes suggest a
positive association among cardiac biomarkers,
cardiac function, and “peripheral”
microvascular disease (11). Finally,
prospective data from ADVANCE have
recently demonstrated that an elevated
resting heart rate (potentially an
early marker of cardiac overload) is
strongly associated with increased risk
of nephropathy and retinopathy (12),
and data fromZwolle Outpatient Diabetes
project Integrating Available Care
(ZODIAC)-33 show that copeptin elevation
predicts albuminuria (13). Thus, early
changes in cardiac biomarkers may precede
presentation with frank microvascular
disease and yield prognostic
information that enables intensive interventions
to be targeted to those at
greatest risk. Developing a clearer understanding
of any relationship between
cardiac function/metabolism and microvascular
end points is important
both from an aetiological perspective
and potentially to develop risk scores
to guide clinical management. We thus
aimed to 1) investigate the association
between biomarkers of cardiac stress
and incident microvascular outcomes
in patients with type 2 diabetes and 2)
investigate the incremental ability of
cardiac biomarkers to predict microvascular
events.