Decreasing Markers Of Inflammation Is As Important For Statin Action As Decreasing Ldl Cholesterol (Jupiter Study)

Main Category: Statins
Also Included In: Cholesterol;  Cardiovascular / Cardiology
Article Date: 03 Apr 2009 - 1:00 PDT

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A follow-up study on the JUPITER* trial has revealed that a key component of the action of statins is reduction of high sensitivity c-reactive protein (hsCRP), a marker of inflammation, as well as reducing levels of bad cholesterol. The findings are published in an Article published Online First and in an upcoming edition of The Lancet. Publication of the Article coincides with the announcement of the findings at the American College of Cardiology (ACC) meeting in Florida, USA.

Present guidelines for statin therapy emphasise the goal of reducing LDL or 'bad' cholesterol. However, statin therapy works best in the presence of inflammation, which is characterised by increased concentrations of the biomarker hsCRP. It is thought that reducing levels of hsCRP helps prevent inflammatory cell adhesion - the process by which inflammation promotes cells sticking together and forming plaques in arteries. Reducing hsCRP could also help by preventing these cells sticking to the endothelium (or inner lining) of the artery, and favourably affect metal-containing enzymes key to plaque stability.

In this study, lead investigator Dr Paul Ridker (Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA, USA) and colleagues followed-up 15,548 initially healthy men and women from the JUPITER study - 87% of the original participants of that trial. They assessed the effects of rosuvastatin 20mg versus placebo on rates of non-fatal heart attack, non-fatal stroke, hospital admission for unstable angina, arterial revascularisation, or cardiovascular death. Concentrations of LDL were measured (≥ 1.8mmol/L or <1.8mmol/L) as was hsCRP (≥2mg/L or < 2mg/L).

The researchers found that, compared with placebo, participants given rosuvastatin who achieved LDL cholesterol less than 1.8 mmol/L had a 55% reduction in vascular events, and those achieving hsCRP less than 2mg/L a 62% reduction. Patients who achieved both LDL less than 1.8 mmol/L and hsCRP less than 2 mg/L saw a 65% reduction in vascular events, versus a 33% reduction in those who achieved only one or neither target. Participants who achieved the LDL target plus a hsCRP concentration of 1 mg/L or less saw a 79% reduction in vascular events. Furthermore, the researchers showed that achieved hsCRP concentrations predicted events even if lipid-based endpoints other than LDL cholesterol concentration were used.

Despite these results, the authors emphasise that for primary prevention in low risk populations, initial interventions 'should remain lifestyle recommendations for dietary restriction, exercise, and smoking cessation'. They conclude: "However, as our findings have shown, for people choosing to start pharmacological prophylaxis, reductions in both LDL cholesterol and hsCRP are indicators of the success of treatment with statin therapy."

In an accompanying Comment, Dr Jean-Pierre Després, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec City, Canada, says: "Despite the fact that regular exercise is a remarkable and cheap 'polypill', a comparison of the absolute reduction in risk for coronary heart disease that is gained after statin treatment versus that with a lifestyle-modification programme aimed at weight loss and improved fitness is unlikely to happen in the near future."

He concludes: "To immediately translate these findings into clinical practice without appropriate and careful discussion of their implications is not prudent. Hopefully, focus on the JUPITER trial will spur constructive and responsible dialogues to prioritise clinical and public health actions for primary prevention of cardiovascular disease."

DOI:10.1016/S0140-6736(09)60447-5
The Lancet

Notes
*JUPITER study= Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin

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Tony Kirby
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The Lancet
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