Mild hyperhomocysteinemia is an independent risk factor for increased carotid artery wall thickness and plaque formation in a general population. Lower levels of dietary folate intake and the C677T mutation in MTHFR are important causes of mild hyperhomocysteinemia and may therefore contribute to vascular disease in the community.

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There is a need for more effective therapies to reduce morbidity and mortality from cardiovascular disease. Inflammation plays a central role in the pathogenesis of atherosclerosis but no randomized studies have evaluated anti-inflammatory therapy in patients with acute coronary or cerebrovascular disease. We performed a pilot randomized controlled trial comparing the effect of colchicine 1 mg per day with placebo on high sensitivity C-reactive protein (CRP) levels and platelet function in 80 patients with acute coronary syndrome or acute ischemic stroke who were followed for 30 days. Clinical status was ascertained for 74 (92.5%) patients and CRP levels were obtained in 68 (85%) of patients at follow up. Colchicine did not significantly reduce absolute hs-CRP at 30 days [median 1.0 mg/l (range 0.2, 162.0) versus 1.5 mg/l (0.2, 19.8), P = 0.22] or difference in CRP from baseline to 30 days [absolute difference 7.0 mg/l (-61.0, 87.8) vs. 7.1 mg/l (-1.0, 144), P = 0.64]. The proportion of patients with CRP <2 mg/l at follow up did not differ according to treatment allocation (77% vs. 62%, X (2) 1.84, P = 0.18). There was also no difference in platelet function assessed using platelet aggregation with ADP (5 μmol), arachidonic acid (0.5 mmol), collagen (1 μg/ml) and collagen (5 μg/ml) (P = 0.86, P = 0.64, P = 0.76, P = 0.20, respectively), and urine dehydrothromboxane B2 (P = 0.54). Colchicine was associated with an excess of diarrhoea (X(2) 4.14, P = 0.04). In conclusion, our pilot study provided no evidence that colchicine 1 mg daily for 30 days compared with placebo suppresses inflammation in patients with acute coronary syndrome or acute ischemic stroke.

Colchicine is a unique, sophisticated anti-inflammatory agent that has been used for decades for the prevention of acute inflammatory flares in gout and familial Mediterranean fever. In recent years, clinical trials have demonstrated its potential in a range of cardiovascular (CV) conditions. Colchicine is avidly taken up by leucocytes, and its ability to bind to tubulin and interfere with microtubular function affects the expression of cytokines and interleukins, and the ability of neutrophils to marginate, ingress, aggregate, express superoxide, release neutrophil extracellular traps, and interact with platelets. In patients with acute and recurrent pericarditis, clinical trials in &gt;1600 patients have consistently shown that colchicine halves the risk of recurrence [relative risk (RR) 0.50, 95% confidence interval (CI) 0.42–0.60]. In patients with acute and chronic coronary syndromes, multicentre randomized controlled trials in &gt;11 000 patients followed for up to 5 years demonstrated that colchicine may reduce the risk of CV death, myocardial infarction, ischaemic stroke and ischaemia-driven revascularization by &gt;30% (RR 0.63, 95% CI 0.49–0.81). The use of colchicine at doses of 0.5–1.0 mg daily in CV trials has proved safe. Early gastrointestinal intolerance limits its use in ∼10% of patients; however, ∼90% of patients tolerate it well over the long term. Despite isolated case reports, clinically relevant drug interactions with moderate to strong CYP3A4 inhibitors/competitors or P-glycoprotein inhibitors/competitors are rare if this dosage of colchicine is used in the absence of advanced renal or liver disease. The aim of this review is to summarize the contemporary data supporting the efficacy and safety of colchicine in patients with CV disease.

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Abstract-The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with an increased risk of coronary heart disease, but whether it is a risk factor for underlying atherosclerosis remains unclear. Therefore, we examined to see whether the ACE gene deletion polymorphism was associated with carotid wall thickening and atherosclerotic plaque formation in a large randomly selected community population. A total of 1111 subjects, aged 27 to 77 years, with an equal male:female ratio and equal numbers in each age decile, were randomly selected from the Perth community population. Mean common carotid intima-medial wall thickness (IMT) and focal plaque formation were assessed by high-resolution B-mode ultrasound.

No abstract