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VOLUME 11 NUMBER 4 • NOVEMBER 2014
151
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
Excess cardiovascular risk in patients with type 2 diabetes:
do we need to look beyond LDL cholesterol?
ALAN REES
Correspondence to: Dr Alan Rees
Department of Medicine, University Hospital of Wales, Cardiff, UK
Tel: +44 (0)29 20743000
e-mail:
alan.rees2@wales.nhs.ukPreviously published in
Br J Diabetes Vasc Dis
2014;
14
: 10–20
S Afr J Diabetes Vasc Dis
2014;
11
: 151–159
Abstract
Despite impressive advances in treatment, cardiovascular
disease (CVD) remains a significant healthcare burden in
the UK and worldwide. The clustering of CVD risk factors
in patients with type 2 diabetes underlines the need for a
multifactorial treatment approach, yet even when receiving
optimal therapy according to best standards of care, there
remains a substantial risk of CVD and microvascular disease.
Risk-prediction tools traditionally provide an estimate of
risk over 10 years, however this approach is dominated by
chronological age and gender and has a number of recognised
limitations. A move from 10-year to lifetime risk calculation
has been proposed, and should encourage intervention at a
much earlier stage. This move, alongside aggressive and broad
control of modifiable risk factors, aims to ease the burden of
atherosclerosis prior to the manifestations of CVD. This will
be of particular benefit to those with type 2 diabetes, who
have been exposed to hyperglycaemia and other risk factors
for extended periods of time. The atherogenic dyslipidaemia
common in this group also ensures they will benefit most from
treatment strategies under investigation to further reduce
macro- and microvascular risk.
Keywords:
residual risk, cardiovascular disease, type 2 diabetes,
lifetime risk, atherogenic dyslipidaemia, macrovascular
Introduction
Annual mortality from cardiovascular disease (CVD) has almost
halved in the UK in the last 50 years, to about 180 000 people in
2009 – representing a fall from 51 to 32% of all-cause mortality.
1
Nevertheless, CVD remains the leading cause of death both in the
UK1 and world wide.
2
However, this progressive decrease in CVD
mortality is being attenuated by the counterbalancing increase in
obesity, the metabolic syndrome and type 2 diabetes.
The prevalence of obesity has been increasing exponentially
over the past two decades,
3
and is the most prevalent metabolic
disease worldwide.
4
This increase in obesity is fuelling a rise in the
numbers of people with metabolic syndrome or type 2 diabetes,
5,6
with prevalence estimates for the metabolic syndrome varying
between 20 and 30% of adults
7
and diabetes affecting 8.3% of the
global population.
5,8
Until recently type 2 diabetes was considered
to be a disease of adulthood, however over the past two decades
an increase in children and adolescents has been reported – from
< 3% of all cases of new-onset diabetes in adolescents in 1990 to
45% in 2005.
9
Young people with this disorder have an increased
risk of morbidity and mortality during the most productive years of
life.
10,11
As coronary disease is the major cause of death associated
with diabetes,
12,13
it may be expected that the observed mortality
decline would also be reflected in patients with diabetes. However,
a large cohort study based in the USA showed that cardiovascular
mortality rates in men with diabetes have not decreased to the
same extent as those seen in the general population, and have even
increased among women.
14
The combined increase in prevalence of obesity, the metabolic
syndrome and diabetes is having tangible effects on coronary
heart disease (CHD) mortality. Recent epidemiological data from
1984 to 2004 in the UK show a significant overall reduction in
CHD mortality among adults, but in younger men, mortality rates
increased in 2002 for the first time in over two decades. This was
reflected in data for both men and women aged 45 to 54 where a
slowing of the decline in mortality rates was observed, with trends
reflected in data from the USA.
15
Unfavourable trends in risk factors
for CHD were considered a likely explanation for the observed
mortality rates.
15,16
The increasing prevalence of diabetes and its attendant CVD
risk makes management of this disease and its complications
of paramount importance. Type 2 diabetes is a complex disease
defined by hyperglycaemia due to insulin resistance and progressive
beta-cell failure. Among the first studies to confirm independent
associations between glycated haemoglobin (HbA
1c
) and vascular
complications, including cardiovascular complications, were the
landmark UKPDS (UK Prospective Diabetes Study)
17
and its long-term
follow-up analysis.
18
This association has also been highlighted in
a number of large population-based observational studies,
19-21
and
was subsequently quantified in a large meta-analysis including data
from almost 700 000 patients. The meta-analysis found that serum
glucose is independently associated with an increased risk of CHD
(HR: 2.00, 95% CI: 1.83–2.19), ischaemic stroke (HR: 2.27, 95%
CI: 1.95–2.65) and an aggregate of other vascular deaths (HR:
1.73, 95% C:I 1.51–1.98).
22
The financial burden of excess CVD in type 2 diabetes
The cost burden of diabetes mellitus to the National Health Service
(NHS) is estimated to be up to 10% of the total resource expenditure,
with a recent study estimating the annual cost in 2010/2011 to be
around £9.8 billion.
23
Type 2 diabetes was responsible for around
90% of this cost, with less than a quarter relating to the treatment
and ongoing management of diabetes and the remainder accounted
for by treating its complications.
23
The large hospital-care burden is a
result of the treatment of retinal, renal, neuropathic, cerebrovascular
and cardiac complications, which occur with increasing frequency
and severity as the disease progresses.
24
For example, a study conducted into secondary care treatment
for patients with diabetes in Wales found that those with diabetes
represented over a quarter of nephrology admissions and almost