Comment 1148 www.thelancet.com Vol 373 April 4, 2009 is an important mediator of the clinical benefits of rosuvastatin. However, 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. How can we delineate the proper population to treat? When should we use C-reactive protein in clinical practice? These issues will have to be examined carefully. Jean-Pierre Després Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec City, QC, Canada G1V 4G5 Jean-Pierre.Despres@criucpq.ulaval.ca J-PD has been a speaker for Abbott Laboratories, AstraZeneca, Solvay Pharma, GlaxoSmithKline, and Pfizer Canada; has received research funding from Innodia, Eli Lilly, GlaxoSmithKline, and Sanofi-Aventis; is on advisory boards for MSD, Novartis, and Sanofi-Aventis; and has received consulting fees from Innodia and Sanofi-Aventis. 1 Ridker PM, Danielson E, Fonseca FAH, et al, on behalf of the JUPITER Trial Study Group. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 2009; published online March 29, 2009. DOI:10.1016/S0140-6736(09)60447-5. Fourth-generation fluoroquinolones in tuberculosis Drug development against Mycobacterium tuberculosis has been an overlooked area of tuberculosis research for some time. The first breakthrough—to obtain an active antituberculosis agent—occurred in the mid-1940s with the seemingly reluctant discovery of the activity of streptomycin 1 and the more focused path towards the synthesis of para-aminosalicylic acid. 2 The second breakthrough came when three drug companies simultaneously and independently applied to patent isonicotinic acid hydrazide (now known as isoniazid), only to learn that this drug had already been synthesised 50 years earlier. 3 The third and perhaps last specific attempt at finding an antituberculosis agent came with the isolation of an antibiotic from the rifamycin class, published in 1959. 4 Almost two decades passed before a regimen based on isoniazid plus rifampicin underwent rigorous assessment. 5 Just 3 years after the identification of the rifamycins, nalidixic acid was synthesised. 6 This agent was the starting point from which the later fluoroquinolones were developed. Fluoroquinolones were found to have activity against M tuberculosis and would become the first real competitors of the two most powerful classes of antituberculosis agents that are now in routine use. Although nearly all fluoroquinolones have antimycobacterial activity, the fourth generation, which includes gatifloxacin and moxifloxacin, have a particularly strong activity against M tuberculosis. In The Lancet today, Marcus Conde and colleagues 7 report the effect on sputum-culture conversion at 8 weeks of treatment with isoniazid, rifampicin, and pyrazinamide given in combination with either moxifloxacin or ethambutol (control). Ethambutol does not enhance, or only minimally enhances, the activity of the combination of isoniazid, rifampicin, and pyrazinamide against a fully susceptible strain. Indeed, so far, no drug has substantially enhanced the activity of this three-drug combination. The trial’s finding that culture conversion to negative occurred in 80% of patients in the moxifloxacin See Editorial page 1145 See Articles page 1183 2 Ridker PM, Danielson E, Fonseca FAH, et al, for the JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359: 2195–207. 3 Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002; 105: 1135–43. 4 Ridker PM, Rifai N, Cook NR, Bradwin G, Buring JE. Non-HDL cholesterol, apolipoproteins A-I and B 100 , standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. JAMA 2005; 294: 326–33. 5 Hak AE, Stehouwer CD, Bots ML, et al. Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women. Arterioscler Thromb Vasc Biol 1999; 19: 1986–91. 6 Lemieux I, Pascot A, Prud’homme D, et al. Elevated C-reactive protein: another component of the atherothrombotic profile of abdominal obesity. Arterioscler Thromb Vasc Biol 2001; 21: 961–67. 7 Church TS, Barlow CE, Earnest CP, Kampert JB, Priest EL, Blair SN. Associations between cardiorespiratory fitness and C-reactive protein in men. Arterioscler Thromb Vasc Biol 2002; 22: 1869–76. 8 Ridker PM, Buring JE, Cook NR, Rifai N. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women. Circulation 2003; 107: 391–97. 9 Tracy RP, Psaty BM, Macy E, et al. Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects. Arterioscler Thromb Vasc Biol 1997; 17: 2167–76. 10 Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005; 366: 1267–78. 11 Després J-P, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006; 444: 881–87. 12 Sui X, LaMonte MJ, Blair SN. Cardiorespiratory fitness as a predictor of nonfatal cardiovascular events in asymptomatic women and men. Am J Epidemiol 2007; 165: 1413–23.