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Effective prevention and treatment of atherosclerosis and cardiovascular disease (CVD), the commonest cause of death in most countries, is still lacking. For many years we have studied the cholesterol hypothesis and found that there are many contradictions to this hypothesis. For instance, no trial has shown exposure response; the lipid values are not associated with degree of atherosclerosis, and people with high LDL-C live just as long or longer than people with low LDL-C. These facts together with the observation that inflammation is a common finding in atherosclerotic arteries have probably contributed to the hypothesis that CVD may be caused by inflammation. However, several trials with anti-inflammatory drugs have shown that such treatment increases the risk of CVD. Therefore, a relevant hypothesis is whether it is infections which cause the inflammation and whether CVD may be caused by infections because many human observations and animal experiments are in accordance with this idea. As cholesterol-lowering treatment is ineffective and may cause serious side effects, we believe that future research should elucidate the importance of infections in the etiology of CVD. A relevant method would be to perform a blood culture on all patients with an acute AMI and if it is positive, to treat the patient with an appropriate antibiotic.