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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 3, May/June 2018
AFRICA
191
cardiovascular mortality (standard mortality ratio: 0.83, 90%
CI: 0.7–1.0).
39
In another study comparing over 15 000 patients
and over 27 000 controls, PsO was found to be an equivocal risk
factor for admission for ischaemic heart disease (IHD), after
controlling for age and gender (HR
=
1.10, 95% CI: 0.99–1.23).
40
Moreover, age- and gender-matched survival analysis revealed
no difference in the risk of acute MI.
A recent Dutch study of 262 ambulatory PsO patients over 55
years of age showed no increase in CV morbidity and mortality.
41
The strength of this study was that CV events were identified
using clinical data and specialised investigations, including
CT scans, and electro- and echocardiography to minimise
classification bias (all previous studies had used diagnostic
codes). However, the limitations of this study were the small
sample size, older age of the cohort (mean
=
64 years), and that
most patients had mild cutaneous PsO. Overall, the balance of
evidence suggests that PsO, especially severe cutaneous disease,
is associated with an increased risk of CVD.
Other metabolic disorders shown to occur more frequently
in PsO are the MetS (and its components), hyperuricaemia,
and non-alcoholic fatty liver disease (NAFLD). In a UK study,
the MetS was more prevalent in PsO patients compared to
the general population, more so in patients with severe than
with mild cutaneous disease (OR for mild PsO
=
1.22, 95% CI:
1.11–1.35; severe PsO
=
1.98, 95% CI: 1.62–2.43).
13
Furthermore,
systematic reviews suggest that individual components of the
MetS (dysglycaemia, obesity and hypertension) occur more
frequently in PsO patients
15,42,43
(Table 4).
A meta-analysis of 16 observational studies found that PsO
patients were more likely to be obese (pooled OR
=
1.66, 95%
CI: 1.17–1.82).
15
A combined mean BMI of 30.6 kg/m
2
has been
observed in a review of clinical trials where biologics have been
tested for the treatment of moderate to severe cutaneous PsO.
44
Studies have also shown that PsO is associated with abdominal
obesity, which is a proxy measure of visceral adipose tissue, and is
a well-recognised risk factor for T2DM, hypertension, coronary
artery disease and decreased life expectancy.
45
The prospective
Nurses’ Health Study II identified 809 incident cases of PsO and
observed that it was more common in subjects with an increased
waist circumference, a surrogate marker for abdominal visceral
fat.
46
In a cross-sectional case–control study, subjects with PsO
were shown to have higher levels of visceral fat measured by
computed tomography (CT) compared to controls.
47
The role of
visceral fat in chronic inflammation is discussed below.
Several studies have shown an increased prevalence of
hypertriglyceridaemia in PsO patients.
13,16,18
Comparisons of
total cholesterol (TC) and low-density lipoprotein cholesterol
(LDL-C) between patients and controls have yielded conflicting
results. Some studies show an increase in TC and LDL-C levels
in PsO patients compared to controls,
18
whereas others show
no significant differences or decreased levels.
48
Asymptomatic
hyperuricaemia is more common in PsO, even after correcting
for confounders (age, gender and features of the MetS).
23
Likewise, the risk of gout is also increased in PsO and PsA (HR
=
1.71, 95% CI: 1.36–2.15).
49
Several studies have demonstrated an increased prevalence
of NAFLD in subjects with PsO.
22
The diagnostic methods
used in these studies included ultrasonography, biochemistry,
transient elastography, liver biopsy, or combinations thereof. The
prevalence of NAFLD was 65.6 versus 35% in matched controls
(
p
<
0.001) when measured by ultrasonography.
50
Pathophysiological basis linking psoriasis
with cardiometabolic disease
Inflammation: the common denominator
There is now overwhelming evidence that chronic sub-clinical
systemic inflammation accelerates atherosclerosis,
29
including
histological studies demonstrating the presence of inflammation
in atherosclerotic lesions.
53
Both innate and adaptive immunity
are known to play a role in this process.
30
This has been well-
documented in type 2 diabetes,
54
and also in RA
34
and systemic
lupus erythematosus.
55
Further evidence linking inflammation
to atheroslcerosis is that C-reactive protein (CRP), a well-
recognised biomarker of inflammation, is also associated with
atherothrombotic disease, aswell as theMetS and its components.
56
As PsO is a systemic disease, the prevailing pro-inflammatory
milieu is considered to contribute to the increased CMD risk.
57
A
meta-analysis of 78 studies found significantly elevated levels of
pro-inflammatory cytokines, namely IL-6, TNF, CRP, E-selectin
and ICAM 1, in PsO patients compared to controls.
58
Obesity, which, as discussed previously, is prevalent in subjects
with PsO, is a further source of inflammation. White adipose
tissue (WAT), which is the primary component of visceral fat, is
composed of both adipocytes and other immunologically active
cells such as macrophages.
59
Hence it is both metabolically and
immunologically active. Adipocytes secrete adipokines, which
are mainly pro-inflammatory, such as leptin, visfatin and resistin;
as well adiponectin, which has anti-inflammatory properties.
59
Other pro-inflammatory factors that are produced by WAT
include TNF, IL-1, IL-6 and plasminogen activator inhibitor
type 1 (PAI-1), all of which have been shown to directly or
indirectly affect endothelial cell function and insulin sensitivity.
60
Possible genetic links
Epidemiological studies suggest a common genetic link between
PsO, T2DM and obesity. In a 2016 cross-sectional, population-
based twin study in 33 588 Danish subjects, a significant
association between PsO, T2DM and obesity was observed.
61
Analysing data from twins discordant for PsO and including
both monozygotic and dizygotic twin pairs, the study observed
evidence for a shared genetic aetiology of obesity and PsO.
Moreover, there is evidence indicating that the strongest
predictor of major adverse cardiovascular events (MACE) in
patients with PsO is a family history of CVD.
62
In a study of
more than 25 000 mainly young Danes with mild PsO, and over
4 000 patients with severe disease, approximately two-thirds
of patients in each group had a family history of CVD. The
adjusted incidence rate ratios of MACE (with 95% CI) in
patients with a family history of cardiovascular events were
1.28 (1.12–1.46) in those with mild PsO, and 1.62 (1.14–2.30) in
Table 4. Systematic reviews showing association of type 2 diabetes,
hypertension and obesity with psoriasis
Risk factor
No of
studies
Odds ratio
Overall
Mild PsO Severe PsO
Type 2 diabetes
42
27 1.59 (1.38–1.83) 1.53 (1.16–2.04) 1.97 (1.48–2.62)
Hypertension
43
24 1.58 (1.42–1.76) 1.30 (1.15–1.47) 1.49 (1.20–1.86)
Obesity
15
16 1.66 (1.49–1.89) 1.46 (1.17–1.82) 2.23 (1.63–2.05)