Prevalence of atherosclerotic risk factors and the metabolic syndrome in patients with chronic inflammatory arthritis

Abstract

Objective

To evaluate the prevalence of the metabolic syndrome in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA).

Methods

Consecutive patients with RA, AS, or PsA who attended our outpatient arthritis clinics between July and November 2009 were recruited for a study of atherosclerotic risk factors and the metabolic syndrome, defined according to the 2009 joint statements using the Asian criteria for central obesity.

Results

Nine hundred thirty patients were studied (699 with RA, 122 with AS, and 109 with PsA; 70% women, mean ± SD age 51.1 ± 12.7 years). The mean ± SD disease duration for patients with RA, AS, and PsA was 5.3 ± 5.4, 6.0 ± 5.6, and 3.6 ± 3.1 years, respectively. The prevalence of metabolic syndrome was significantly higher in PsA (38%) than RA (20%) or AS (11%; P < 0.001). The odds ratios (ORs) for the metabolic syndrome compared to age- and sex-matched controls were 0.98 (95% confidence interval [95% CI] 0.78–1.23, P = 0.88), 0.59 (95% CI 0.30–1.15, P = 0.12), and 2.68 (95% CI 1.60–4.50, P < 0.001), respectively, for RA, AS, and PsA. Patients with PsA had a significantly higher prevalence of impaired fasting glucose (30%; P < 0.001), low high-density lipoprotein (HDL) cholesterol (33%; P < 0.001), high triglycerides level (21%; P = 0.008), central obesity (65%; P < 0.001), and high blood pressure (56%; P = 0.045). In a logistic regression model, the adjusted OR for the metabolic syndrome in PsA was 2.44 (95% CI 1.48–4.01, P < 0.001) relative to RA or AS. The adjusted ORs for central obesity, impaired fasting glucose, hypertriglyceridemia, and low HDL cholesterol were also significantly higher in PsA patients.

Conclusion

Patients with PsA, but not RA or AS, have a significantly higher prevalence of the metabolic syndrome compared to the general population. Among the 3 diseases studied, PsA has the highest prevalence of the metabolic syndrome and is associated with the highest cardiovascular risk.

INTRODUCTION

Patients with chronic inflammatory arthritis such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are prone to accelerated atherosclerosis and its complications (1–3). Population studies have shown that the standardized incidence ratios of cerebrovascular disease and symptomatic ischemic heart disease were 1.6, 1.3, and 1.7 and 1.5, 1.3, and 1.2, respectively, for RA, PsA, and AS (4). The increased risk of atherosclerotic vascular disease compared to the age- and sex-matched general population in patients with chronic inflammatory arthritis is contributed by an increased prevalence of traditional vascular risk factors such as obesity, hypertension, dyslipidemia, and impaired glucose tolerance (5). However, as shown by studies in RA and PsA, the increased risk of arterial thrombosis cannot be solely accounted for by the increase in traditional risk factors (6, 7). Disease- and treatment-related factors such as persistent elevation of proinflammatory cytokines, chronic treatment with glucocorticoids, calcineurin inhibitors, and the nonsteroidal antiinflammatory drugs may also be responsible for the increased cardiovascular risk.

The metabolic syndrome is a cluster of traditional risk factors that include abdominal obesity, atherogenic dyslipidemia, hypertension, and insulin resistance (8). The presence of the metabolic syndrome is a strong predictor for type 2 diabetes mellitus, stroke, and cardiovascular diseases (9, 10), although there remains controversy if the metabolic syndrome is a distinct entity and whether the predictive value of the metabolic syndrome for cardiovascular risk is higher than that expected from individual risk factors alone (11). The prevalence of the metabolic syndrome, as defined by the National Cholesterol Education Program Adult Treatment Panel III (8), has been reported to be significantly higher in patients with RA (12), skin psoriasis (13, 14), and AS (15, 16) as compared to the general population. Of particular interest is psoriasis, in which the prevalence of abdominal obesity and the metabolic syndrome is relatively high compared to RA (13, 14). There is still little information regarding the incidence of obesity and the metabolic syndrome in patients with PsA.

In view of the increased prevalence of vascular risk factors in patients with chronic inflammatory arthritis, we conducted the present study to compare the prevalence of traditional risk factors and the metabolic syndrome in our outpatient arthritis clinics.

PATIENTS AND METHODS

Study population.

Consecutive patients with chronic inflammatory arthritis who attended the outpatient arthritis clinics of Pok Oi Hospital between July 1 and November 15, 2009, were recruited for assessment of traditional atherosclerotic risk factors and body measurements for abdominal obesity. The inclusion criteria were: 1) patients who fulfilled the 1987 American College of Rheumatology classification criteria for RA (17), the modified New York criteria for AS (18), or the CASPAR (ClASsification criteria for Psoriatic ARthritis) group criteria for PsA (19); 2) age ≥18 years; and 3) patients who were able to give informed consent. Exclusion criteria consisted of: 1) patients with uncertain diagnosis; 2) patients with rheumatic diagnoses other than RA, AS, and PsA; and 3) patients who refused to participate in this study.

Clinical assessment for vascular risk factors.

All of the patients who attended our arthritis clinics within the study period were screened. Basic demographic characteristics and disease diagnoses were recorded for each participant. Traditional vascular risk factors were assessed by a direct face-to-face interview using a questionnaire and medical record review by a nurse specialist in our outpatient clinics. These factors included history of past and current smoking, history of habitual drinking, and history of hypertension, diabetes mellitus, and dyslipidemia. Blood pressure was measured and fasting blood was taken for assay of glucose and lipid levels (total cholesterol, high-density lipoprotein [HDL] and low-density lipoprotein [LDL] cholesterol, and triglycerides level). Body weight, body height, and waist and hip circumferences were also measured.

Definition for the metabolic syndrome.

The metabolic syndrome was defined by the updated joint consensus criteria proposed by the International Diabetes Federation Task Force on Epidemiology and Prevention, the National Heart, Lung, and Blood Institute, the American Heart Association, the World Heart Federation, the International Atherosclerosis Society, and the International Association for the Study of Obesity (20), using the Asian criteria for central obesity (21) when ≥3 of the following components were present: 1) increased waist circumference to ≥90 cm in men or ≥80 cm in women, 2) elevated blood pressure to ≥130/85 mm Hg or requiring drug therapy, 3) elevated serum triglycerides level to ≥1.7 mmoles/liter, 4) reduced serum HDL cholesterol to ≤1.0 mmoles/liter in men and ≤1.3 mmoles/liter in women, and 5) elevated fasting glucose level to ≥5.6 mmoles/liter.

Data analyses and statistical methods.

The demographic characteristics, prevalence of various vascular risk factors, and the metabolic syndrome were compared among patients with the 3 inflammatory arthritic conditions and with the age- and sex-matched healthy population by using data collected from a community health survey (22). We first stratified the control data set according to age range (by 10-year interval) and sex. The subjects in each stratum were then randomly selected by computer with a case to control ratio of 1:2. The odds ratios (ORs) of each of the 3 rheumatic diseases for the metabolic syndrome were calculated. Comparison of the prevalence of the metabolic syndrome was also made between those patients with early arthritis (within 24 months of diagnosis) and established disease (diagnosed more than 24 months prior to study entry).

Unless otherwise stated, values were expressed as the mean ± SD. Continuous variables were compared by the one-way analysis of variance (ANOVA) test. Post hoc multiple comparison among patients with RA, AS, and PsA was performed by Tukey's test for unequal samples. Categorical variables were compared by using the nonparametric Kruskal-Wallis H test. The ORs for the metabolic syndrome were calculated for each of RA, AS, and PsA with respect to the age- and sex-matched population. A logistic regression model was constructed for the OR of the metabolic syndrome in PsA with respect to RA or AS patients with adjustment of age, sex, disease duration, use of biologics, and other vascular risk factors not included in the definition of the metabolic syndrome.

Statistical significance was defined as a 2-tailed P value of less than 0.05. All of the statistical analyses were performed using the SPSS program, version 11.5, for Windows XP.

RESULTS

Study population characteristics.

One thousand eighty patients were screened, but only 940 patients fulfilled the inclusion criteria. Ten patients refused to participate and finally, 930 patients consented for the study. The underlying diagnoses of the participants were RA (n = 699), AS (n = 122), and PsA (n = 109). Of these 930 patients, there were 649 (70%) women and 281 (30%) men. The mean ± SD age at the time of screening was 51.1 ± 12.7 years. The mean ± SD disease duration for patients with RA, AS, and PsA was 5.3 ± 5.4, 6.0 ± 5.6, and 3.6 ± 3.1 years, respectively.

Table 1 shows the demographics and disease duration of the patients recruited. A female predominance was observed in RA patients, whereas men predominated in patients with AS. PsA had a roughly equal sex incidence. Patients with AS were younger compared to RA and PsA. The disease duration was significantly shorter in patients with PsA than RA (P = 0.005) or AS (P = 0.002). The proportion of patients with early disease (≤2 years) was also significantly higher in PsA (P = 0.03).

Table 1. Demographics and disease duration of the patients studied*

	RA (n = 699)	AS (n = 122)	PsA (n = 109)	P†	Post hoc test P‡
* RA = rheumatoid arthritis; AS = ankylosing spondylitis; PsA = psoriatic arthritis. † Derived from one-way analysis of variance (continuous variables) or Kruskal-Wallis H tests (categorical variables). ‡ Post hoc multiple comparison of continuous variables was performed by Tukey's test.
Women, no. (%)	566 (81)	28 (23)	55 (50)	< 0.001	–
Age, mean ± SD years	53.3 ± 12.0	39.0 ± 11.8	50.4 ± 10.6	< 0.001
RA vs. AS					< 0.001
PsA vs. AS					< 0.001
Disease duration, mean ± SD years	5.3 ± 5.4	6.0 ± 5.6	3.6 ± 3.1	0.001
RA vs. PsA					0.005
AS vs. PsA					0.002
Disease duration ≤2 years, no. (%)	205 (29)	27 (22)	41 (38)	0.03	–

At the time of the screening, 452 patients (65%) with RA were receiving methotrexate, 104 patients (15%) were receiving leflunomide, 296 patients (42%) were receiving sulphasalazine, 289 patients (41%) were receiving hydroxychloroquine, and 94 patients (13%) were receiving low-dose prednisolone. One hundred sixteen patients (17%) were receiving ≥3 noncorticosteroid disease-modifying antirheumatic drugs (DMARDs) and 48 patients (7%) were receiving biologic agents (67% anti–tumor necrosis factor α [anti-TNFα] agents, 21% tocilizumab, and 12% rituximab) for disease control. Twenty-eight patients (23%) with AS and 10 patients (9%) with PsA were receiving anti-TNFα treatment. The frequencies of use of DMARDs in patients with PsA were as follows: methotrexate (69%), leflunomide (8%), sulphasalazine (22%), and cyclosporin A (4%). Sixteen patients (15%) were receiving ≥2 DMARDs.

Prevalence of the metabolic syndrome and vascular risk factors.

Table 2 shows the prevalence of vascular risk factors and the metabolic syndrome of all of the participants. The overall prevalence of the metabolic syndrome was 21%, with the highest figure for PsA (38%), followed by RA (20%) and AS (11%). The prevalence of metabolic syndrome was significantly higher in PsA than the other two rheumatic diseases (P < 0.001).

Table 2. Prevalence of vascular risk factors and the metabolic syndrome*

	RA (n = 699)	AS (n = 122)	PsA (n = 109)	P†
* Values are the mean ± SD unless otherwise indicated. RA = rheumatoid arthritis; AS = ankylosing spondylitis; PsA = psoriatic arthritis; HDL = high-density lipoprotein; LDL = low-density lipoprotein. † Derived from one-way analysis of variance (continuous variables) or Kruskal-Wallis H tests (categorical variables).
Risk factors included in the metabolic syndrome, no. (%)
Waist ≥80 cm in women or ≥90 cm in men	370 (53)	45 (37)	71 (65)	< 0.001
Blood pressure ≥130/85 mm Hg or under treatment	363 (52)	50 (41)	61 (56)	0.045
Triglycerides level ≥1.7 mmoles/liter	83 (12)	10 (8)	23 (21)	0.008
HDL cholesterol ≤1.3 mmoles/liter in women or ≤1.0 mmoles/liter in men	119 (17)	16 (13)	36 (33)	< 0.001
Fasting glucose ≥5.6 mmoles/liter	111 (16)	11 (9)	33 (30)	< 0.001
Prevalence of the metabolic syndrome	137 (20)	13 (11)	41 (38)	< 0.001
Vascular risk factors
Daily smoking ≥3 years, no. (%)	109 (16)	36 (30)	21 (19)	0.001
Body weight, kg	57.2 ± 10.0	63.5 ± 13.3	65.5 ± 11.7	< 0.001
Body height, meters	1.57 ± 0.08	1.65 ± 0.08	1.61 ± 0.08	< 0.001
Body mass index, kg/m^2	23.3 ± 4.2	23.3 ± 4.4	25.2 ± 4.1	< 0.001
Body mass index >27 kg/m^2, no. (%)	107 (15)	20 (16)	31 (28)	0.004
Waist circumference, cm	82.7 ± 11.0	83.8 ± 12.0	89.3 ± 10.4	< 0.001
Hip circumference, cm	95.6 ± 7.7	96.5 ± 8.1	99.2 ± 7.7	< 0.001
Total cholesterol level, mmoles/liter	5.17 ± 1.06	5.07 ± 1.08	5.23 ± 1.06	0.58
LDL cholesterol level, mmoles/liter	3.06 ± 0.87	3.19 ± 1.04	3.26 ± 0.91	0.09
HDL cholesterol level, mmoles/liter	1.59 ± 0.41	1.43 ± 0.40	1.31 ± 0.36	< 0.001
Triglycerides level, mmoles/liter	1.21 ± 1.79	1.00 ± 0.50	1.43 ± 0.96	0.17
Fasting glucose, mmoles/liter	5.10 ± 1.06	4.98 ± 1.07	5.44 ± 1.19	0.006
Systolic blood pressure, mm Hg	128 ± 18	126 ± 18	130 ± 18	0.21
Diastolic blood pressure, mm Hg	74 ± 11	74 ± 11	76 ± 11	0.18

Regarding the individual criterion for the metabolic syndrome, patients with PsA had a significantly higher prevalence of impaired fasting glucose (30%; P < 0.001), low HDL cholesterol (33%; P < 0.001), high triglycerides level (21%; P = 0.008), central obesity (65%; P < 0.001), and high blood pressure (56%; P = 0.045) compared to the other two diseases. One-way ANOVA with post hoc multiple comparison test revealed a significantly higher body mass index (BMI) in patients with PsA than RA (P < 0.001) or AS (P < 0.001). The body weight and body height were significantly lower in patients with RA than that of AS or PsA (P < 0.001 in all). Moreover, the waist and hip circumferences were significantly higher in PsA than RA or AS patients (P < 0.05 in all). Concerning the lipid levels, PsA patients had higher LDL cholesterol (P = 0.09) and significantly lower HDL cholesterol (P < 0.001) than patients with RA. Fasting glucose level was also significantly higher in PsA than RA patients (P = 0.006).

ORs of the metabolic syndrome compared to the general population.

Table 3 shows the prevalence of the metabolic syndrome of each of the 3 rheumatic diseases compared to the age- and sex-matched general population. The metabolic syndrome was not significantly more common in patients with RA or AS than that of the general population. On the other hand, PsA patients had the highest prevalence of the metabolic syndrome that was significantly higher than that of matched controls. The ORs of having the metabolic syndrome compared to the age- and sex-matched general population were 0.98 (95% confidence interval [95% CI] 0.78–1.23, P = 0.88), 0.59 (95% CI 0.30–1.15, P = 0.12), and 2.68 (95% CI 1.60–4.50, P < 0.001), respectively, for RA, AS, and PsA patients.

Table 3. Prevalence of the metabolic syndrome compared to the general population*

	RA (n = 699)	Controls (n = 1,398)	P	AS (n = 122)	Controls (n = 244)	P	PsA (n = 109)	Controls (n = 218)	P
* Values are the number (percentage) unless otherwise indicated. RA = rheumatoid arthritis; AS = ankylosing spondylitis; PsA = psoriatic arthritis; HDL = high-density lipoprotein.
Age, mean ± SD years	53.3 ± 12.0	52.9 ± 12.0	0.50	39.0 ± 11.8	39.9 ± 10.6	0.51	50.4 ± 10.6	49.7 ± 10.8	0.57
Women	566 (81)	1,132 (81)	1.00	28 (23)	56 (23)	1.00	55 (50)	110 (50)	> 0.99
Criteria for the metabolic syndrome
Waist circumference	370 (53)	425 (30)	< 0.001	44 (36)	65 (27)	0.06	71 (65)	74 (34)	< 0.001
Blood pressure	363 (52)	635 (45)	0.01	50 (41)	97 (40)	0.82	61 (56)	103 (47)	0.48
Triglycerides level	83 (12)	274 (20)	< 0.001	10 (8)	57 (23)	< 0.001	23 (21)	53 (24)	0.41
HDL cholesterol	119 (17)	642 (46)	< 0.001	16 (13)	86 (35)	< 0.001	36 (33)	86 (39)	0.15
Fasting glucose	111 (16)	306 (22)	< 0.001	10 (8)	37 (15)	0.06	33 (30)	51 (23)	0.18
Metabolic syndrome	137 (20)	278 (20)	0.88	13 (11)	41 (17)	0.12	41 (38)	40 (18)	< 0.001

Prevalence of the metabolic syndrome according to disease duration and treatment.

Table 4 shows the prevalence of the metabolic syndrome in the 3 rheumatic diseases with regard to disease duration and treatment. No significant differences in the prevalence of the metabolic syndrome can be observed in patients with early disease (duration of ≤2 years) and established disease in any of the 3 conditions. In patients with PsA, there was a trend of a higher prevalence of the metabolic syndrome in those with a longer disease duration. In patients with RA, treatment with biologic agents was associated with a lower prevalence of metabolic syndrome, but the difference was not statistically significant. Similarly, patients with AS and PsA who were currently receiving anti-TNFα therapies had a trend of lower prevalence of the metabolic syndrome.

Table 4. Prevalence of the metabolic syndrome with regard to disease duration and treatment*

Clinical variables	No. (%)	Metabolic syndrome, no. (%)	P†
* Anti-TNFα = anti–tumor necrosis factor α. † Derived from Fisher's exact test.
Rheumatoid arthritis
Disease duration
≤2 years	206 (29)	45 (22)
>2 years	493 (71)	92 (19)	0.35
Current use of biologic agents	48 (7)	6 (13)
No use of biologic agents	651 (93)	131 (20)	0.26
Ankylosing spondylitis
Disease duration
≤2 years	27 (22)	5 (19)
>2 years	95 (78)	8 (8)	0.16
Current use of anti-TNFα agents	28 (23)	1 (4)
No use of anti-TNFα treatment	94 (77)	12 (13)	0.29
Psoriatic arthritis
Disease duration
≤2 years	41 (38)	14 (34)
>2 years	68 (62)	27 (40)	0.55
Current use of anti-TNFα agents	10 (9)	1 (10)
No use of anti-TNFα treatment	99 (91)	49 (49)	0.09

ORs for the metabolic syndrome and atherosclerotic risk factors in PsA.

Table 5 shows the results of a logistic regression model for the OR of the metabolic syndrome in patients with PsA compared to RA or AS, with adjustment for age, sex, chronic smoking, BMI, disease duration, and current treatment with biologic agents. The adjusted OR for the metabolic syndrome in PsA patients was 2.44 (95% CI 1.48–4.01) compared to RA or AS patients (P < 0.001).

Table 5. A logistic regression model of the OR of the metabolic syndrome in PsA*

Covariates	OR (95% CI)	P
* OR = odds ratio; PsA = psoriatic arthritis; 95% CI = 95% confidence interval; non-PsA = rheumatoid arthritis or ankylosing spondylitis.
PsA vs. non-PsA	2.44 (1.48–4.01)	< 0.001
Age, per year	1.05 (1.04–1.07)	< 0.001
Women	1.18 (0.74–1.87)	0.49
Ever smoking	1.08 (0.62–1.88)	0.79
Body mass index, per kg/m^2	1.21 (1.16–1.26)	< 0.001
Disease duration, per year	0.97 (0.94–1.01)	0.19
Current use of biologic agents	0.58 (0.25–1.33)	0.20

Table 6 shows the ORs for various atherosclerotic risk factors in patients with PsA compared to non-PsA (i.e., RA or AS) after adjustment for age, sex, and disease duration in multivariate models. The prevalence of central obesity, high BMI, impaired glucose tolerance, hypertriglyceridemia, and low HDL cholesterol level was significantly higher in patients with PsA than RA or AS.

Table 6. Adjusted ORs for atherosclerotic risk factors in patients with psoriatic arthritis compared to rheumatoid arthritis or ankylosing spondylitis*

	Adjusted OR (95% CI)†	P
* OR = odds ratio; 95% CI = 95% confidence interval; BMI = body mass index; HDL = high-density lipoprotein; LDL = low-density lipoprotein. † Adjusted for age, sex, and disease duration. ‡ Criteria according to the definition of the metabolic syndrome.
High blood pressure‡	1.25 (0.81–1.93)	0.32
Central obesity‡	2.25 (1.44–3.49)	< 0.001
BMI ≥27 kg/m^2	2.15 (1.34–3.44)	0.001
Impaired fasting glucose‡	2.58 (1.60–4.17)	< 0.001
Hypertriglyceridemia‡	2.08 (1.23–3.53)	0.007
Low HDL cholesterol level‡	2.80 (1.77–4.44)	< 0.001
High LDL cholesterol level (≥2.6 mmoles/liter)	1.65 (0.99–2.77)	0.06
Smoking for ≥3 years	0.60 (0.34–1.07)	0.08

DISCUSSION

This is a cross-sectional study on the prevalence of the metabolic syndrome in a large number of patients with chronic inflammatory arthritis. Our results indicate that metabolic syndrome occurred more frequently in patients with PsA than the general population. Among patients with RA, AS, and PsA, PsA patients show the highest risk for the presence of atherosclerotic risk factors, in particular obesity, impaired glucose tolerance, and hypertriglyceridemia, and hence the metabolic syndrome. There is no significant relationship between the prevalence of the metabolic syndrome and disease duration in the 3 rheumatic diseases studied. The use of anti-TNFα treatment was associated with a trend of lower prevalence of the metabolic syndrome.

The population prevalence of the metabolic syndrome in our locality was reported to be 16.7% in the mid-1990s (23). In another community-based survey (22) conducted in the early 2000s in which control data were retrieved for matching with patients in the current study, the prevalence of the metabolic syndrome was 18.3%. More recent data on the prevalence of the metabolic syndrome in our locality are unavailable, but a rapid change in the prevalence of the metabolic syndrome is not our impression in the past few years. The results of the comparative data between patients and controls in this study were unlikely to be substantially affected. The prevalence of the metabolic syndrome in our locality and in Asian countries is generally lower than that of the US, in which a prevalence of 34% was recently reported by the National Health and Nutrition Examination Survey (24).

The reasons for the increased prevalence of atherosclerotic risk factors and the metabolic syndrome in patients with rheumatic diseases are not totally clear. Organ complications such as renal insufficiency, drug-induced nephropathy, and fluid retention, as well as chronic treatment with glucocorticoids, calcineurin inhibitors, and nonsteroidal antiinflammatory drugs, may contribute to a higher incidence of hypertension, impaired glucose tolerance, dyslipidemia, and visceral obesity. However, with the exception of RA, glucocorticoids are very infrequently used in patients with AS or PsA. The calcineurin inhibitors are second- to third-line agents for the treatment of RA and skin psoriasis, and they are not used for the treatment of AS. Nephropathy with renal function deterioration as a result of uncontrolled disease activity is now less common in inflammatory arthritides with the routine use of DMARDs in the past two decades and the introduction of the biologic agents. Perhaps one of the major causes of the increased prevalence of traditional vascular risk factors is residual disease activity, which leads to persistent elevation of proinflammatory cytokines that contributes to insulin resistance, impaired glucose tolerance, dyslipidemia, and accelerated atherosclerosis.

The interplay among cytokines, disease activity, atherosclerotic risk factors, and metabolic syndrome in patients with chronic inflammatory arthritis is complex. Elevation of the levels of TNFα and interleukin-6 (IL-6) as a result of active arthritis and skin inflammation reduces the activity of insulin and inhibits insulin receptor autophosphorylation and signal transduction (25, 26), thereby promoting insulin resistance that leads to hyperglycemia, compensatory hyperinsulinemia, and dyslipidemia. In visceral obesity, hypertrophic adipocytes are resistant to the lipolytic effect of insulin (27). The resultant increase in the production of nonesterified fatty acids may induce hepatic and peripheral insulin resistance that leads to an increase in hepatic glucose production and hyperglycemia, a decrease in apolipoprotein degradation, and an increase in triacylglycerol-rich lipoproteins (28), as well as an elevation of blood pressure (29).

On the other hand, the abdominal fat may be a source of production of adipocytokines such as TNF-α, IL-6, adiponectin, and plasminogen activator inhibitor type 1 (30). Both TNF-α and IL-6 aggravate the degree of insulin resistance (31). Furthermore, proinflammatory cytokines are involved in the pathogenesis of atherosclerosis. TNF-α, IL-1, and interferon-γ produced by activated immune cells in the atherosclerotic plaque induce the production of substantial amounts of IL-6, which in turn stimulates the hepatic release of acute-phase reactants, including C-reactive protein, serum amyloid A, and fibrinogen (32). Persistent elevation of C-reactive protein levels as a result of uncontrolled inflammatory arthritis is associated with an increased risk of cardiovascular events (33) and all-cause mortality (34).

The increase in the prevalence of atherosclerotic risk factors, in particular obesity, impaired glucose tolerance, and dyslipidemia, and the metabolic syndrome in patients with PsA compared to RA or AS and the general population is an intriguing phenomenon. In addition to synovitis, PsA patients have concomitant inflammatory skin lesions. Both skin and joint inflammation in PsA may aggravate the degree of elevation of proinflammatory cytokines that contributes to insulin resistance, obesity, and dyslipidemia compared to RA or AS. Moreover, obesity and psoriatic skin lesions may share a common dysregulated immunologic pathway. Both obese patients and patients with psoriasis have elevated levels of inflammatory cytokines such as TNFα (35, 36), and there is evidence that more serious and extensive skin psoriasis is associated with a higher relative risk of obesity compared to mild skin disease (37). Certain behavioral changes due to skin psoriasis such as poor eating habits, depression, alcohol consumption, stress, and physical inactivity as a result of psoriasis stigmatization may predispose patients with PsA to obesity (38). Finally, obesity itself may be a predisposing factor for the onset of skin psoriasis. One case–control study has reported that an increased BMI was independently associated with the development of skin psoriasis after adjustment for age, sex, marital status, hospitalization, education level, smoking, and alcohol use (39). The prospective US Nurses' Health Study also reported that increased adiposity and weight gain were strong risk factors for the incident skin psoriasis in women (40). These factors may collectively explain the increased prevalence of obesity and the metabolic syndrome in patients with PsA compared to other inflammatory arthritis such as RA and AS.

Contrary to the study from Chung et al (12), who reported a significant increase in the prevalence of metabolic syndrome in 154 patients with RA compared to 85 controls, we could not demonstrate an increased prevalence of metabolic syndrome in our 651 RA patients. This is consistent with the report from Karvounaris et al (41), who also demonstrated a very similar prevalence of the metabolic syndrome in their RA patients to control subjects. The reasons for these discrepancies are not immediately apparent. While the differences in disease severity and duration of the selected patients in different studies may contribute, the significantly lower prevalence of a low HDL cholesterol level observed in our RA patients than matched controls warrants further exploration.

In addition, we did not find a higher prevalence of metabolic syndrome in our AS patients compared to matched controls. This is contrary to the results of the studies by Papadakis et al (15) and Malesci et al (16). In the former study, patients were receiving anti-TNFα therapies, indicating that they belonged to a more serious disease subgroup. In the latter study, the number of patients was small (n = 24) and they had very longstanding disease (median 16.5 years). Our AS patients had a much shorter disease duration and milder disease activity, as shown by the small proportion of patients receiving anti-TNFα treatment. This might have contributed to a lower prevalence of vascular risk factors.

The anti-TNFα biologics are an effective treatment for inflammatory arthritis. By neutralizing the inflammatory effects of TNFα, these agents have been shown by controlled trials to reduce levels of biomarkers for cardiovascular risk in PsA and RA (42, 43). Despite the fact that patients who required anti-TNFα therapies had more serious disease, we were able to demonstrate a trend of lower prevalence of the metabolic syndrome in users of anti-TNFα agents in all 3 of the rheumatic diseases studied. This supports the notion that persistent inflammation is an aggravating factor for atherosclerotic risk.

In summary, our study confirms that the prevalence of vascular risk factors and the metabolic syndrome is increased in patients with PsA compared to age- and sex-matched controls. Among patients with PsA, RA, and AS, PsA is associated with the highest prevalence of obesity, impaired fasting glucose, and the metabolic syndrome. The limitation of our study is the lack of assessment for subclinical atherosclerosis and data regarding the relationship between clinical disease activity and the prevalence of the metabolic syndrome. Nevertheless, our study emphasizes the need to screen for atherosclerotic risk factors in patients with PsA so that more vigorous control of these risk factors can be instituted early.

AUTHOR CONTRIBUTIONS

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Mok had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Mok.

Acquisition of data. Mok, Ko, Ho, Yu, Chan, To.

Analysis and interpretation of data. Mok, Ko.