C-reactive protein (CRP) associated with risk of coronary heart disease, stroke, vascular mortality, and death from several cancers and lung disease

Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people.

This Lancet meta-analysis included records of 160,309 people without a history of vascular disease from 54 long-term prospective studies.

Risk ratios (RRs) were 1·23 for coronary heart disease; 1·32 for ischaemic stroke; 1·34 for vascular mortality; and 1·34 for non-vascular mortality.

CRP concentration has continuous associations with the risk of:

- coronary heart disease
- ischaemic stroke
- vascular mortality
- death from several cancers and lung disease

The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation.

Is is still a topic of debate is whether CRP has a causal role in the development of cardiovascular disease.

However, even if CRP might not be involved in the causal pathway of atherogenesis and plaque rupture, it may still be a valuable tool in cardiovascular medicine.

In primary prevention, lovastatin therapy was more cost effective in people with increased CRP concentrations.

The JUPITER trial recently showed that, in people with relatively normal LDL cholesterol concentrations and CRP higher than 2 mg/L, rosuvastatin reduced cardiovascular risk. Even if CRP turns out to be not directly causal in cardiovascular disease, it might be useful to identify individuals at cardiovascular risk and to evaluate the efficacy of our preventing and therapeutic interventions.

References:
C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. The Lancet, Volume 375, Issue 9709, Pages 132 - 140, 9 January 2010.
C-reactive protein and cardiovascular risk: more fuel to the fire. S Matthijs Boekholdt a b, John JP Kastelein b. The Lancet, Volume 375, Issue 9709, Pages 95 - 96, 9 January 2010.

C reactive protein concentration itself is unlikely to be even a modest causal factor in coronary heart disease - BMJ, 2011. http://goo.gl/d5lCH
Image source: C-reactive protein. Wikipedia, GNU Free Documentation License.

Celiprolol as treatment of choice to prevent complications in vascular Ehlers-Danlos syndrome

Vascular Ehlers-Danlos syndrome is a rare hereditary connective tissue disorder caused by mutations in the collagen type III gene ( COL3A1 ), which leads to a loss of tissue integrity in many organ systems.

Patients with vascular Ehlers-Danlos syndrome have weakened blood vessels and an increased risk of arterial dissection or rupture that can lead to early death.

The researchers assessed the ability of celiprolol, a β1-adrenoceptor antagonist with a β2-adrenoceptor agonist action, to prevent arterial dissections and ruptures in vascular Ehlers-Danlos syndrome.

Patients with clinical vascular Ehlers-Danlos syndrome were randomly assigned to 5 years of treatment with celiprolol or to no treatment.

33 patients were positive for mutation of collagen 3A1 (COL3A1). Celiprolol was uptitrated every 6 months by steps of 100 mg to a maximum of 400 mg twice daily. The primary endpoints were arterial events (rupture or dissection, fatal or not).

Mean duration of follow-up was 47 months, with the trial stopped early for treatment benefit.

The primary endpoints were reached by 20% in the celiprolol group and by 50% controls (hazard ratio [HR] 0·36).

Celiprolol might be the treatment of choice for physicians aiming to prevent major complications in patients with vascular Ehlers-Danlos syndrome.

References:

Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial. The Lancet, Volume 376, Issue 9751, Pages 1476 - 1484, 30 October 2010.

Celiprolol therapy for vascular Ehlers-Danlos syndrome. The Lancet, Volume 376, Issue 9751, Pages 1443 - 1444, 30 October 2010.