Reducing Cardiovascular Risk in Lupus

Dr D PYNEConsultant Rheumatologist/Clinical Lead

Barts Health NHS Trust Honorary Senior Clinical lecturer Sports & Exercise , QMUL London

Barts LupusCentre

Subclinical Atherosclerosis

Cardiovascular risk factors

50% SLE patients have at least 3

Classical Disease specific

Blood pressure Chronic inflammation

Hyperlipidaemia Steroid use

Diabetes chronic proteinuria

Sedentary Antibodies (eg Antiphospholipid)

Obesity Homocysteine

Smoking

Risk factor ‘Ideal’ target values

Blood pressure <130 mmHg systolic and diastolic <80 mmHgLDL cholesterol <2.6 mmol/lDiabetes mellitus Fasting blood glucose <7.0 mmol/l

Random blood glucose <11.0 mmol/lSmoking Stop smokingObesity Body mass index <25 kg/m2

Additional measures Indications

Aspirin Known vascular diseaseSLE plus one other risk factorAPL Abs (non warfarinised)

ACE inhibitors Prevalent cardiovascular disease Left ventricular hypertrophyDiabetes mellitusPreferred second drug for hypertension

Prevention of cardiovascular disease in systemic lupus erythematosus—proposed guidelines for risk factor management

TABLE 1. Summary of ideal targets for risk factors in patients with SLE

•Rheumatology (Oxford) January 1, 2004 vol. 43 no. 1 7-12

Guidelines for managing CV disease in Lupus

• EULAR 2008 Management Lupus

‘Despite the lack of SLE-specific literature, weight control, physical exercise and smoking cessation are recommended. Statins and antihypertensives (ACE inhibitors) should also be considered in selected patients’

• ACR Lupus nephritis 2012

The Task Force Panel recommended that careful attention be paid to control of hypertension, with a target of ≤ 130/80

The Panel also recommended that statin therapy be introduced in patients with LDL cholesterol >100 mg/dL (2.6 mmol/l) (Level C)

The ABCDEF of Cardiovascular risk management in SLE

A ?

B ?

C ?

D ?

E ?

F ?

The A of Cardiovascular risk management in SLE

ASPIRIN

SLE studies

• No RCTs• APLASA trial –ve study• Cohort studies suggest HCQ + Asp benefit SLE + APL Abs

General Population

• 9 primary prevention RCTs studies

My practice- Aspirin for secondary prevention. I don’t routinely use for primary prevention in SLE

Aspirin in men Aspirin in women (2 trials) & Aspirin in diabetics (2 trials)

•32% relative risk reduction for MI •No effect on all-cause mortality

No effect on MI or all-cause mortality

ACE INHIBITORS /ARB

• No RCTs in SLE

• 50% SLE have nephritis – proteinuria is main feature

• Proteinuria associated with an approximate 50% increase in coronary risk (risk ratio 1.47, 95% confidence interval [CI] 1.23–1.74)

• RAS blockade intraglomerular pressure proteinuria 30%

Use ACE-I or ARB if chronic persistent proteinuria

The A of Cardiovascular risk management in SLE

The B of Cardiovascular risk management in SLE

BLOOD PRESSURE

Target 130/80

A – ACE –I/ ARB - if proteinuric / known IHD

B- B Blockers - used less (Raynauds, Blacks)

C- Calcium Antagonists (amlodipine)

D – Diuretics (thiazides, spirinolactone)

Most Black patients need combination drugs – A+C most commonly

The Cs of Cardiovascular risk management in SLE

CHOLESTEROLNICE Guidance : Lipid Modification July 2014

‘Non-high density lipoprotein (non-HDL) cholesterol is seen to be a better cardiovascular disease (CVD) risk indicator than low-density lipoprotein (LDL) cholesterol. It is more accurate, more practical and cost effective. A fasting blood sample is not needed’

European Society of Cardiology guidelines (2011)

If non-HDL-C is used, the target should be <3.4 mmol/L (less than 130 mg/dL) in ∼those at high total CV risk

Offer Atorvastatin 20mg for primary prevention - more potent than other non-generic statins and has a lower risk of adverse interactions with other drugs, does not have to be taken at night.

The Cs of Cardiovascular risk management in SLE

HYDROXYCHLOROQUINE

• May have anti platelet properties Achuthan et al Hydroxychloroquine's Efficacy as an Antiplatelet Agent Study in Healthy Volunteers: A Proof of Concept Study. J Cardiovasc Pharmacol Ther. 2015 Mar;20(2):174-80

Consider HCQ in all SLE patients

The Cs of Cardiovascular risk management in SLE

CIGARETTES

The Ds of Cardiovascular risk management in SLE

DIABETES

WHO guidance on diabetes 2011

• HbA1c can be used as a diagnostic test for diabetes

• HbA1c of 6.5% = diabetes

• HbA1c level between 6.0 and 6.5% are at particularly high risk and might be considered for diabetes prevention interventions

Keep hbA1C < 6%

The Ds of Cardiovascular risk management in SLE

DIETICIAN

Overweight definition = BMI>25

BMI (body mass index kg/m2)

BUT……………………..

Figure 6. YLL relative to WHtR 0.46 in female non-smokers.

Ashwell M, Mayhew L, Richardson J, Rickayzen B (Sept 2014) Waist-to-Height Ratio Is More Predictive of Years of Life Lost than Body Mass Index. PLoS ONE 9(9): e103483. doi:10.1371/journal.pone.0103483http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103483

Citation: Ashwell M, et al(2014) Waist-to-Height Ratio Is More Predictive of Years of Life Lost than Body Mass Index. PLoS ONE 9(9): e103483.

PAI:

ActiveModerately ActiveModerately InactiveInactive

The E of Cardiovascular risk management in SLE

EXERCISE

31

14 17

36

0

10

20

30

40

50

60

Active Moderately Active Moderately Inactive Inactive

Lupus

Consecutive patients age 30-50yr attending GP surgery

N=100

N=100Malliotis N, Wykes F, Pyne D Rheumatology (2015) 54 (s1): 203-204.

The E of Cardiovascular risk management in SLE

FOLATE

• Raised homocysteine (>15 μmol/L) in 15% SLE• Assoc with x3 risk arterial thromboses (OD (3·49 [0·97–12·54], p=0·05)

Petri M etal Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus Lancet 348, 9035, 1120–11241996, 1996

Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators N Engl J Med 2006; 354:1567-157, 2006

The F of Cardiovascular risk management in SLE

Ensure normal folate/B12 levels

A Aspirin / ACE-I / ARB

B Blood pressure 130-140/80-90

C Cholesterol (Non- HDL <3.4 ), HydroxyChloroquine (all) , Cigarette cessation

D Diabetes (HbA1c <6%) , Dietician (W:Ht <0.5)

E Exercise (Aerobic)

F Folate

Lupus – Cardiovascular Risk management

Note- lack of evidence base

THANK YOU