Malattie infiammatorie
croniche e coronaropatia
Enrico Natale
I UO Cardiologia, Ospedale S.Camillo, Roma
Factors contributing to CV disease
Genetic profile
Co-morbidities
Demographic
•Age
•Family Hx
Risk factors
•Hypertension
•DM
•IGF/IGT
•Metabolic syndrome
•Dyslipidemia
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CV diseases
•Chronic inflammatory
diseases
•Headache/Migraine
•Psychic disorders
•Hyperuricemia/Gout
CV/renal disease
•CHD
•Stroke/AIT
•Atrial fibrillation
•PAD
•Renal failure
Malattie infiammatorie croniche
Articolari: artrite reumatoide
Multisistemiche: m. autoimmuni sistemiche,
vasculiti sistemiche
Gastrointestinali: m. di Crohn, RCU
Cutanee: psoriasi, dermopatie bollose
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Perché aumenta il rischio
cardiovascolare
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Pathways and cytokines by which synovitis can contribute to the
formation of an atherosclerotic plaque and eventually CV events
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van den Oever IAM, et Al: Ther Adv Musculoskel Dis 2013;5:166–181
THE LINK BETWEEN COAGULATION AND INFLAMMATION
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van den Oever IAM, et Al: Ann Rheum Dis 2014;0:1–4.
Epidemiologia
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Incidence of major CV diseases and age in
patients with and without RA
(British Columbia Residents)
CVD is the main cause of mortality in RA pts, accounting for as much as 50% of all deaths
The risk for experiencing a first CV event is increased by as much as 60% in RA pts,
especially for MI, reducing the average lifespan by as much as 18 yrs
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Solomon et Al, Ann Rheum Dis 2006
Does rheumatoid arthritis equal diabetes mellitus
as an independent risk factor for cardiovascular disease?
A prospective study
Cardiovascular event-free probability to 3 years
nondiabe
tic contro
ls
type
2 dia
betes
nond
iab
etic p
ts wit
h
melli
tus p
ts
type 2 diabetes mellitus: HR 2.0 (95%CI,1.1–3.7)
nondiabetic pts with RA: HR 2.2 (95% CI, 1.3–3.6)
Peters MJL, et Al: Arthritis Rheum 2009; 61:1571–1579
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RA
Recommendations for lipid profiling in order to assess total CV risk
RA, SLE, PsA are associated
with increased CV risk
ESC/EAS Guidelines for the
Management of dyslipidaemias
EHJ 2011
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Inflammatory bowel disease and CV events
Comparison of the rates of CAD events in IBD pts with matched controls
a longitudinal cohort study of patients with IBD
IBD patients had significantly lower rates
of selected traditional CAD risk factors
(hypertension, diabetes, dyslipidemia, and obesity; P<0.01 for all).
Adjusting for these factors,
the HR for developing CAD between groups was 4.08 (95% CI 2.49-6.70).
Yarur AJ, et al: Am J Gastroenterol
2011;106:741
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Risk of atrial fibrillation and stroke in rheumatoid arthritis:
Danish nationwide cohort study
Rates of AF in general population and patients with RA
+40%
Lindhardsen J, et al: BMJ 2012;344:e1257
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Risk of atrial fibrillation and stroke in rheumatoid arthritis:
Danish nationwide cohort study
Rates of stroke in general population and patients with RA
+30%
Lindhardsen J, et al: BMJ 2012;344:e1257
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UK Clinical Practice Research Datalink (CPRD)
The CPRD is the world’s largest primary care database comprising anonymized longitudinal
electronic patient records from primary care. Cohorts of participants aged >18 years with
selected chronic inflammatory disorders recorded between January 1, 2002, and January
31, 2013, and without prior T2DM or prevalent CVD were sampled from the CPRD. All
participants had at least 12 months of follow-up recorded, and outcomes of interest were
only considered after the first 12 months of the follow-up.
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Chronic inflammatory disorders included in the study
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Dregan A et al: Circulation 2014; 130:837
Adjusted HR (95% CI) of DM, Stroke, Coronary Heart Disease, and Multimorbidity (≥2
Outcomes) in Different Chronic Inflammatory Disorders Compared With Matched Controls
Absolute risk of outcome events for CHD per 1000 pts: 5.12 (pts with chronic
inflammation) vs 4.06 (control cohort) with the same age and sex distribution
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Dregan A et al: Circulation 2014; 130:837
Influence of chronic inflammatory conditions on multiple CV and T2DM outcomes
Forest plot displaying random-effects meta-analysis
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Dregan A et al: Circulation 2014; 130:837
Dose–Response Relationship Between Tertiles
of Mean CRP Levels and Study Outcome
On the basis of these data, a threshold level of ≈10 mg/L could help to identify
pts with inflammation at increased risk of CVD and T2DM in primary care
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Dregan A et al: Circulation 2014; 130:837
Malattie infiammatorie croniche e coronaropatia
Ruolo dei fattori di rischio CV tradizionali
Rischio cardiovascolare e età insorgenza/durata malattia
Sono utili gli score di rischio cardiovascolare ?
E’ possibile prevenire gli eventi cardiovascolari ?
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Ruolo dei fattori di rischio
CV tradizionali
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Prevalence of HBP in cross-sectional surveys in
patients with RA and controls
P<0.05
P<0.05
P<0.05
Panoulas VF et al, Rheumatology 2008
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Cardiovascular disease/risk factors among pts with PsA (n.3066)
(1,2)
(1,5)
Han et Al, J Rheumatol 2006
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(1,3)
Relative impact of traditional CV risk factors on combined
CV end point in pts with RA and non-RA subjects
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Gabriel SE. Ann Rheum Dis 2010;69(Suppl1):i61–4
LOW BODY MASS INDEX AND CARDIOVASCULAR MORTALITY IN RA
2 states of cachexia in RA:
rheumatoid cachexia (low muscle
and high fat mass), and
classic low BMI cachexia ( low
muscle and low fat mass).
Kremers HM, et al: Arthitis & Rheumatism 2004;50: 3450–3457
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Gabriel SE et al:
Ann Rheum Dis 2010;69:i61-4
Toms TE et al:
Curr Vasc Pharmacol 2010;8:301-6
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Conroy RM, et al:
Eur Heart J 2003;24:987–1003
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Ital Heart J 2003; 4: 281-284
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Il rischio cardiovascolare
correla con durata della
malattia ed età alla diagnosi
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Overview of studies
on symptomatic CV
disease risk during
the first decade of RA
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Kerola AM, et al: Ann Rheum Dis 2012;71:1606–1615
Disease factors in early rheumatoid arthritis are associated with differential risks for CV
events and mortality depending on age at onset: A 10-year observational cohort study
Better Anti-Rheumatic Pharmaco Therapy (BARFOT) early RA cohort, recruited 19931999
pts aged ≥ 65
pts aged < 65
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Ajeganova S, et al: J Rheumatol 2013;40:1958–66
Disease factors in early rheumatoid arthritis are associated with differential risks for CV
events and mortality depending on age at onset: A 10-year observational cohort study
pts aged ≥ 65
pts aged < 65
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Ajeganova S, et al: J Rheumatol 2013;40:1958–66
Sono utili gli score di rischio
cardiovascolare
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Performance of four current risk algorithms in predicting CV events in pts with early RA
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Systematic Coronary
Risk Evaluation
Framingham risk score
Reynolds risk score
QRisk II
Arts EEA, et al: Ann Rheum Dis 2014;0:1–7
EULAR evidence-based recommendations for CV risk management
in patients with RA and other forms of inflammatory arthritis
European League Against Rheumatism
4. Risk score models should be adapted for patients with RA by introducing a
1.5 multiplication factor. This multiplication factor should be used when the
pt with RA meets two of the following three criteria:
•Disease duration of more than 10 years
•RF or anti-CCP positivity
•Presence of certain extra-articular manifestations
Peters MJL, et al: Ann Rheum Dis 2010;69:325–331
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E’ possibile prevenire gli eventi
cardiovascolari
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Cardiovascular mortality by ever use of NSAID
in pts with inflammatory polyarthritis
Goodson NJ, et al: Ann Rheum Dis 2009;68:367-72
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Prednisone was associated with an increased risk of myocardial infarction
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Wolfe F and Michaud K: ARTHRITIS & RHEUMATISM 2008;58:2612–
2621
The effect of methotrexate on CV disease in pts with RA:
a systematic literature review
Westlake SL, et al: Rheumatology 2010;49:295–307
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The effect of methotrexate on CV disease in pts with RA:
a systematic literature review
2 studies assessed the relationship between MTX
use and CVD mortality: 1 demonstrated a
significant reduction in CVD mortality and 1 a
trend towards reduction.
5 studies considered all-cause CVD morbidity:
4 demonstrated a significant reduction in CVD
morbidity and 1 a trend towards reduction.
MTX use in the year prior to the development of
RA decreased the risk of CVD for 3-4 years.
4 studies considered myocardial infarction: 1
demonstrated a decreased risk and 3 a trend
towards decreased risk with MTX use.
Westlake SL, et al: Rheumatology 2010;49:295–307
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Tumour necrosis factor antagonists and the risk of CV disease
in pts with RA: a systematic literature review
Westlake SL, et al: Rheumatology 2011;50:518–531
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Tumour necrosis factor antagonists and the risk of CV disease
in pts with RA: a systematic literature review
reassuringly in the majority of patients are not associated
with an increased risk of heart failure.
Westlake SL, et al: Rheumatology 2011;50:518–531
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Systematic Review and Meta-Analysis: AntiTNF Therapy and CV Events in RA
ES (CI 95%)
weight %
All CV
events
ES (CI 95%)
Myocardial
infarction
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Barnabe C, et al: Arthritis Care & Research 2011;63:522–529
weight %
TNF antagonist use and associated RR of CV events among pts with RA
on behalf of the CORRONA Investigators
Adjusted risk of composite CV events by DMARD and steroid exposure
Greenberg JD, et al: Ann Rheum Dis 2011;70:576–582
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EULAR evidence-based recommendations for CV risk management
in patients with RA and other forms of inflammatory arthritis
The 10 recommendations:
European League Against Rheumatism
1. RA should be regarded as a condition associated with higher risk for CV
disease. This may also apply to AS and PsA, although the evidence base is less.
The increased risk appears to be due to both an increased prevalence of
traditional risk factors and the inflammatory burden.
2. Adequate control of disease activity is necessary to lower the CV risk (best
evidence for anti-tumour necrosis factor treatment and methotrexate treatment).
3. CV risk assessment using national guidelines is recommended for all pts with
RA and should be considered annually for all pts with AS and PsA. Risk
assessments should be repeated when antirheumatic treatment has been changed
(in absence of national guidelines the SCORE function model is recommended).
4. Risk score models should be adapted for patients with RA by introducing a 1.5
multiplication factor. This multiplication factor should be used when the pt with RA
meets two of the following three criteria:
•Disease duration of more than 10 years
•RF or anti-CCP positivity
•Presence of certain extra-articular manifestations
Peters MJL, et al: Ann Rheum Dis 2010;69:325–331
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EULAR evidence-based recommendations for CV risk management
in patients with RA and other forms of inflammatory arthritis
European League Against Rheumatism
The 10 recommendations:
5. Total cholesterol/HDL cholesterol ratio should be used when the SCORE model
is used.
6. Intervention should be carried out according to national guidelines.
7. Statins, ACE-inhibitors and/or angiotensin II blockers are preferred treatment
options due to their potential anti-inflammatory effects.
8. The role of cyclo-oxygenase-2 inhibitors and most non-steroidal anti-inflammatory
drugs in CV risk is not well established and needs further investigation. Hence, we
should be very cautious about prescribing them, especially for patients with a
documented CV disease or in the presence of CV risk factors.
9. Corticosteroids: use the lowest dose possible
10. Recommend smoking cessation
Peters MJL, et al: Ann Rheum Dis 2010;69:325–331
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EULAR Recommended Medications in RA
European League Against Rheumatism
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Key points
People with RA/chronic inflammatory disorders (CID) are at excess
risk for CVD.
Systemic inflammation and its interplay with traditional
and nontraditional CV risk factors appear to have a major role.
CV risk scores developed for the general population are unlikely
to accurately estimate CV risk in RA/CID.
Effective and even optimal control of traditional risk
factors is imperative but insufficient to reduce CV risk for
people with RA/CID. Tight control of systemic inflammation is
likely to be required for optimal results.
Future research should focus on further delineating the
underlying biological mechanisms involved, developing
and evaluating RA-specific risk assessment tools and
biomarkers, as well as prevention and treatment
strategies specific to the RA/CID population.
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Risk of atrial fibrillation and stroke in rheumatoid arthritis:
Danish nationwide cohort study
What this study adds
Patients with rheumatoid arthritis had a 40% higher risk of atrial
fibrillation compared with the general population
The risk of stroke was increased by 30% in rheumatoid arthritis
compared with the general population
The study suggests that increased focus on atrial fibrillation in the
cardiovascular risk assessment of patients with rheumatoid arthritis is
warranted
To what extent the increased risk of AF contributed to the increased risk
of stroke in RA pts was not clear owing to a limited follow-up in these
cases, but no major effect modification was noted, which indicated that
RA was a risk factor for stroke beyond the increased risk of AF.
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Lindhardsen J, et al: BMJ 2012;344:e1257
Prevalence of carotid plaques in pts with SLE, RA and controls*
(*) adjusted for age, gender and CV risk factors
Salmon & Roman, Am J Med 2008
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Changes in IMT, age and duration of the disease in pts with RA
(0,295 mm/10 yrs)
(0,154 mm/10 yrs)
Del Rincon et Al, Atherosclerosis 2007
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Panoulas VF et al, Rheumatology 2008
Mechanisms through which drugs used in RA affect BP
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Panoulas VF et al, Rheumatology 2008
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Revisione sistematica del rischio cardiovascolare nei pazienti con AR
Meune et Al, Arch Cardiovasc Dis 2010
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