Colchicine exerts anti-atherosclerotic and -plaque-stabilizing effects targeting foam cell formation.

Colchicine is a broad-acting anti-inflammatory agent that has attracted interest for repurposing in atherosclerotic cardiovascular disease. Here, we studied its ability at a human equivalent dose of 0.5 mg/day to modify plaque formation and composition in murine atherosclerosis and investigated its actions on macrophage responses to atherogenic stimuli in vitro. In atherosclerosis induced by high-cholesterol diet, Apoe-/- mice treated with colchicine had 50% reduction in aortic oil Red O+ plaque area compared to saline control (p = .001) and lower oil Red O+ staining of aortic sinus lesions (p = .03). In vitro, addition of 10 nM colchicine inhibited foam cell formation from murine and human macrophages after treatment with oxidized LDL (ox-LDL). Mechanistically, colchicine downregulated glycosylation and surface expression of the ox-LDL uptake receptor, CD36, and reduced CD36+ staining in aortic sinus plaques. It also decreased macrophage uptake of cholesterol crystals, resulting in lower intracellular lysosomal activity, inhibition of the NLRP3 inflammasome, and reduced secretion of IL-1ß and IL-18. Colchicine's anti-atherosclerotic actions were accentuated in a mouse model of unstable plaque induced by carotid artery tandem stenosis surgery, where it decreased lesion size by 48% (p = .01), reduced lipid (p = .006) and necrotic core area (p = .007), increased collagen content and cap-to-necrotic core ratio (p = .05), and attenuated plaque neutrophil extracellular traps (p < .001). At low dose, colchicine's effects were not accompanied by the evidence of microtubule depolymerization. Together, these results show that colchicine exerts anti-atherosclerotic and plaque-stabilizing effects at low dose by inhibiting foam cell formation and cholesterol crystal-induced inflammation. This provides a new framework to support its repurposing for atherosclerotic cardiovascular disease.

Association of Low-Dose Colchicine With Incidence of Knee and Hip Replacements : Exploratory Analyses From a Randomized, Controlled, Double-Blind Trial.

BACKGROUND: Osteoarthritis is a major contributor to pain and disability worldwide. Given that inflammation plays an important role in the development of osteoarthritis, anti-inflammatory drugs may slow disease progression. OBJECTIVE: To examine whether colchicine, 0.5 mg daily, reduces incident total knee replacements (TKRs) and total hip replacements (THRs). DESIGN: Exploratory analysis of the LoDoCo2 (Low-Dose Colchicine 2) randomized, controlled, double-blind trial. (Australian New Zealand Clinical Trials Registry: ACTRN12614000093684). SETTING: 43 centers in Australia and the Netherlands. PATIENTS: 5522 patients with chronic coronary artery disease. INTERVENTION: Colchicine, 0.5 mg, or placebo once daily. MEASUREMENTS: The primary outcome was time to first TKR or THR since randomization. All analyses were performed on an intention-to-treat basis. RESULTS: A total of 2762 patients received colchicine and 2760 received placebo during a median follow-up of 28.6 months. During the trial, TKR or THR was performed in 68 patients (2.5%) in the colchicine group and 97 (3.5%) in the placebo group (incidence rate, 0.90 vs. 1.30 per 100 person-years; incidence rate difference, -0.40 [95% CI, -0.74 to -0.06] per 100 person-years; hazard ratio, 0.69 [CI, 0.51 to 0.95]). In sensitivity analyses, similar results were obtained when patients with gout at baseline were excluded and when joint replacements that occurred in the first 3 and 6 months of follow-up were omitted. LIMITATION: LoDoCo2 was not designed to investigate the effect of colchicine in osteoarthritis of the knee or hip and did not collect information specifically on osteoarthritis. CONCLUSION: In this exploratory analysis of the LoDoCo2 trial, use of colchicine, 0.5 mg daily, was associated with a lower incidence of TKR and THR. Further investigation of colchicine therapy to slow disease progression in osteoarthritis is warranted. PRIMARY FUNDING SOURCE: None.

Colchicine in Patients with Chronic Coronary Disease.

BACKGROUND: Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited. METHODS: In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke. RESULTS: A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P<0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31). CONCLUSIONS: In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.).

Measures of carotid atherosclerosis and fall-related hospitalization risk: The Perth Longitudinal Study of Ageing Women.

BACKGROUND AND AIMS: We and others have identified links between cardiovascular conditions and poor musculoskeletal health. However, the relationship between measures of carotid atherosclerosis such as focal carotid plaque and common carotid intima media thickness (CCA-IMT) and falls remains understudied. This study examined the association between measures of carotid atherosclerosis and fall-related hospitalization over 11.5 years in community dwelling older women. METHODS AND RESULTS: 1116 older women recruited in 1998 to a five-year randomized controlled trial to examine the effect of calcium supplementation in preventing fracture and who had undertaken B-mode ultrasound in 2001 (three years after the baseline clinical visit) were included in this study. The participants were followed for over 11.5 years as Perth Longitudinal Study of Ageing Women (PLSAW). Over the follow up period, 428 (38.4%) women experienced a fall-related hospitalization. Older women with carotid plaque had 44% a higher relative hazard for fall-related hospitalization (HR 1.44; 95%CI, 1.18 to 1.76) compared to those without carotid plaque. The association persisted after adjustment for established falls risk factors such as measures of muscle strength and physical function.Each SD increase in the mean and maximum CCA-IMT was also associated with a higher risk of fall-related hospitalizations (HR 1.10; 95%CI, 1.00 to 1.21 and HR 1.11; 95%CI, 1.01 to 1.22, respectively). CONCLUSIONS: Measures of carotid atherosclerosis are associated with a higher risk of fall-related hospitalization independent of established falls risk factors. These findings suggest the importance of vascular health when considering falls risk.

Assessing the Impact of Colchicine on Coronary Plaque Phenotype After Myocardial Infarction with Optical Coherence Tomography: Rationale and Design of the COCOMO-ACS Study.

INTRODUCTION: Recurrent event rates after myocardial infarction (MI) remain unacceptably high, in part because of the continued growth and destabilization of residual coronary atherosclerotic plaques, which may occur despite lipid-lowering therapy. Inflammation is an important contributor to this ongoing risk. Recent studies have shown that the broad-acting anti-inflammatory agent, colchicine, may reduce adverse cardiovascular events in patients post-MI, although the mechanistic basis for this remains unclear. Advances in endovascular arterial wall imaging have allowed detailed characterization of the burden and compositional phenotype of coronary plaque, along with its natural history and responsiveness to treatment. One such example has been the use of optical coherence tomography (OCT) to demonstrate the plaque-stabilizing effects of statins on both fibrous cap thickness and the size of lipid pools within plaque. METHODS: The Phase 2, multi-centre, double-blind colchicine for coronary plaque modification in acute coronary syndrome (COCOMO-ACS) study will evaluate the effect of colchicine 0.5 mg daily on coronary plaque features using serial OCT imaging in patients following MI. Recruitment for the trial has been completed with 64 participants with non-ST elevation MI randomized 1:1 to colchicine or placebo in addition to guideline recommended therapies, including high-intensity statins. The primary endpoint is the effect of colchicine on the minimal fibrous cap thickness of non-culprit plaque over an 18-month period. The COCOMO-ACS study will determine whether addition of colchicine 0.5 mg daily to standard post-MI treatment has incremental benefits on high-risk features of coronary artery plaques. If confirmed, this will provide new mechanistic insights into how colchicine may confer clinical benefits in patients with atherosclerotic cardiovascular disease. TRIAL REGISTRATION: ANZCTR trial registration number: ACTRN12618000809235. Date of trial registration: 11th of May 2018.

Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials.

AIMS: Recent randomized trials demonstrated a benefit of low-dose colchicine added to guideline-based treatment in patients with recent myocardial infarction or chronic coronary disease. We performed a systematic review and meta-analysis to obtain best estimates of the effects of colchicine on major adverse cardiovascular events (MACE). METHODS AND RESULTS: We searched the literature for randomized clinical trials of long-term colchicine in patients with atherosclerosis published up to 1 September 2020. The primary efficacy endpoint was MACE, the composite of myocardial infarction, stroke, or cardiovascular death. We combined the results of five trials that included 11 816 patients. The primary endpoint occurred in 578 patients. Colchicine reduced the risk for the primary endpoint by 25% [relative risk (RR) 0.75, 95% confidence interval (CI) 0.61-0.92; P = 0.005], myocardial infarction by 22% (RR 0.78, 95% CI 0.64-0.94; P = 0.010), stroke by 46% (RR 0.54, 95% CI 0.34-0.86; P = 0.009), and coronary revascularization by 23% (RR 0.77, 95% CI 0.66-0.90; P < 0.001). We observed no difference in all-cause death (RR 1.08, 95% CI 0.71-1.62; P = 0.73), with a lower incidence of cardiovascular death (RR 0.82, 95% CI 0.55-1.23; P = 0.34) counterbalanced by a higher incidence of non-cardiovascular death (RR 1.38, 95% CI 0.99-1.92; P = 0.060). CONCLUSION: Our meta-analysis indicates that low-dose colchicine reduced the risk of MACE as well as that of myocardial infarction, stroke, and the need for coronary revascularization in a broad spectrum of patients with coronary disease. There was no difference in all-cause mortality and fewer cardiovascular deaths were counterbalanced by more non-cardiovascular deaths.

Vegetable diversity in relation with subclinical atherosclerosis and 15-year atherosclerotic vascular disease deaths in older adult women.

PURPOSE: Increasing vegetable intake and diversity are recommended to maintain better health. Evidence for the health benefits of vegetable diversity, separate from total intake, is scarce. We aimed to investigate the associations of vegetable diversity with subclinical measures of atherosclerosis and atherosclerotic vascular disease (ASVD) mortality. METHODS: Vegetable diversity was assessed within a validated food frequency questionnaire using a single question, 'How many different vegetables do you usually consume each day (< 1 to ≥ 6 per day)'. Cox proportional hazards modelling was used to examine the association between vegetable diversity and ASVD mortality in 1226 women aged ≥ 70 years without clinical ASVD or diabetes mellitus at baseline (1998). In 2001, B-mode ultrasonography was used to measure common carotid artery intima-media thickness (CCA-IMT) (n = 954) and carotid plaque severity (n = 968). RESULTS: Over 15 years (15,947 person-years) of follow-up, 238 ASVD-related deaths were recorded. For each additional different vegetable consumed per day, there was 17% lower hazard for ASVD mortality (HR = 0.83, 95% CI 0.78, 0.93, P = 0.001); a 1.7% lower mean CCA-IMT (B ± SE: - 0.013 ± 0.004, P < 0.001); and a 1.8% lower maximum CCA-IMT (B ± SE: - 0.017 ± 0.004, P < 0.001). Further adjustment for total vegetable intake attenuated the association between vegetable diversity and ASVD mortality (P = 0.114), but not CCA-IMT (P = 0.024). No association was observed between vegetable diversity and carotid plaque severity (P > 0.05). CONCLUSIONS: Vegetable diversity may contribute to benefits in lowering risk of ASVD in older women. The reduction in risk is partly explained by increased total vegetable consumption. CLINICAL TRIAL REGISTRY: The Perth Longitudinal Study of Aging in Women (PLSAW) trial registration ID is ACTRN12617000640303. This study was retrospectively registered on the Australian New Zealand Clinical Trials Registry at http://www.anzctr.org.au.

The effect of low-dose colchicine in patients with stable coronary artery disease: The LoDoCo2 trial rationale, design, and baseline characteristics.

Because patients with stable coronary artery disease are at continued risk of major atherosclerotic events despite effective secondary prevention strategies, there is a need to continue to develop additional safe, effective and well-tolerated therapies for secondary prevention of cardiovascular disease. RATIONALE AND DESIGN: The LoDoCo (Low Dose Colchicine) pilot trial showed that the anti-inflammatory drug colchicine 0.5 mg once daily appears safe and effective for secondary prevention of cardiovascular disease. Colchicine's low cost and long-term safety suggest that if its efficacy can be confirmed in a rigorous trial, repurposing it for secondary prevention of cardiovascular disease would have the potential to impact the global burden of cardiovascular disease. LoDoCo2 is an investigator-initiated, international, multicentre, double-blind, event driven trial in which 5522 patients with stable coronary artery disease tolerant to colchicine during a 30-day run-in phase have been randomized to colchicine 0.5 mg daily or matching placebo on a background of optimal medical therapy. The study will have 90% power to detect a 30% reduction in the composite primary endpoint: cardiovascular death, myocardial infarction, ischemic stroke and ischemia-driven coronary revascularization. Adverse events potentially related to the use of colchicine will also be collected, including late gastrointestinal intolerance, neuropathy, myopathy, myositis, and neutropenia. CONCLUSION: The LoDoCo2 Trial will provide information on the efficacy and safety of low-dose colchicine for secondary prevention in patients with stable coronary artery disease.

The Effect of Media Campaigns, Patient Characteristics, and Presenting Symptoms on Prehospital Delay in Myocardial Infarction Patients: A Prospective Cohort Study.

BACKGROUND: Delays in reperfusion therapy for myocardial infarction (MI) are associated with increased mortality and morbidity, and most of this delay is due to delay in patients initiating contact with emergency services. This study assesses the impact of the Australian National Heart Foundation media campaign and identifies patient characteristics and presenting symptoms that may contribute to delay. METHODS: This prospective cohort study identified patients with a diagnosis of MI admitted to a single tertiary metropolitan hospital in Perth, Western Australia from July 2013 to January 2014. Patients were interviewed and responses were categorised to determine their reasons for delaying treatment and the impact of mass media campaigns. Delay times were analysed using multivariable linear regression models for the Whole Cohort (all patients admitted to the tertiary hospital, including patients from rural and peripheral hospitals) and the Direct Admission Cohort (patients admitted directly to the tertiary hospital). RESULTS: Of 376 patients, 255 patients provided consent, and symptom onset-time was available for 175 patients. While almost two thirds of the cohort was aware of media campaigns, awareness was not associated with decreased prehospital delay. Median delay was 3.9hours for the Whole Cohort and 3.5hours for the Direct Admission Cohort. Delay was associated with being widowed, symptom onset on a weekday compared with weekend, past medical history of MI and coronary artery bypass graft, private compared with ambulance transport to hospital, and lack of symptoms of sweating and weakness. In addition, for the Direct Admission Cohort, age and income were also associated with delay. CONCLUSIONS: This study did not find an association between awareness of media campaigns and delay. This study identified important characteristics and presenting symptoms that are associated with delay, and possibly relevant to future media campaigns.

Colchicine: an affordable anti-inflammatory agent for atherosclerosis.

PURPOSE OF REVIEW: Inflammation has been shown to be central to the development and progression of atherosclerosis. Despite detailed understanding of its central role and the cellular dynamics, which contribute to atherosclerotic inflammation, there has been slow progress in finding suitable agents to treat it. The recent CANTOS trial showed that the interleukin-1ß inhibitor canakinumab can improve outcomes after acute coronary syndromes. Being a monoclonal antibody, it is expensive and inconvenient to administer for long-term treatment. This review summarizes recent work in finding effective, affordable alternatives to canakinumab. RECENT FINDINGS: Statin drugs have anti-inflammatory properties but separating their LDL lowering effect from their anti-inflammatory effect has been difficult. Drugs acting on targets outside of the interleukin-1ß (IL-1ß) pathway have been tested without finding a suitable candidate. Following the proof of principle provided by the success of canakinumab, other candidates targeting the IL-1ß pathway are undergoing detailed evaluation. The most likely candidates are low-dose methotrexate and low-dose colchicine. The potential mechanisms and ongoing clinical trials are described. SUMMARY: Targeting the IL-1ß pathway has already been successful with canakinumab but its expense and inconvenience of administration may limit its widespread uptake for controlling inflammation in atherosclerosis. Low-dose methotrexate and low-dose colchicine are affordable and more accessible alternatives, currently undergoing detailed evaluation for safety and efficacy in large randomized controlled trials.

Long-Term Effectiveness and Safety of Pravastatin in Patients With Coronary Heart Disease: Sixteen Years of Follow-Up of the LIPID Study.

BACKGROUND: We aimed to assess the long-term effects of treatment with statin therapy on all-cause mortality, cause-specific mortality, and cancer incidence from extended follow-up of the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) trial. METHODS AND RESULTS: LIPID initially compared pravastatin and placebo over 6 years in 9014 patients with previous coronary heart disease. After the double-blind period, all patients were offered open-label statin therapy. Data were obtained over a further 10 years from 7721 patients, by direct contact for 2 years, by questionnaires thereafter, and from mortality and cancer registries. During extended follow-up, 85% assigned pravastatin and 84% assigned placebo took statin therapy. Patients assigned pravastatin maintained a significantly lower risk of death from coronary heart disease (relative risk [RR] 0.89; 95% confidence interval [CI], 0.81-0.97; P=0.009), from cardiovascular disease (RR, 0.88; 95% CI, 0.81-0.95; P=0.002), and from any cause (RR, 0.91; 95% CI, 0.85-0.97; absolute risk reduction, 2.6%; P=0.003).Cancer incidence was similar by original treatment group during the double-blind period (RR, 0.94; 95% CI, 0.82-1.08; P=0.41), later follow-up (RR, 1.02; 95% CI, 0.91-1.14; P=0.74), and overall (RR, 0.99; 95% CI, 0.91-1.08; P=0.83). There were no significant differences in cancer mortality, or in the incidence of organ-specific cancers. Cancer findings were confirmed in a meta-analysis with other large statin trials with extended follow-up. CONCLUSIONS: In LIPID, the absolute survival benefit from 6 years of pravastatin treatment appeared to be maintained for the next 10 years, with a similar risk of death among survivors in both groups after the initial period. Treatment with statins does not influence cancer or death from noncardiovascular causes during long-term follow-up.

Association of Vegetable Nitrate Intake With Carotid Atherosclerosis and Ischemic Cerebrovascular Disease in Older Women.

BACKGROUND AND PURPOSE: A short-term increase in dietary nitrate (NO3-) improves markers of vascular health via formation of nitric oxide and other bioactive nitrogen oxides. Whether this translates into long-term vascular disease risk reduction has yet to be examined. We investigated the association of vegetable-derived nitrate intake with common carotid artery intima-media thickness (CCA-IMT), plaque severity, and ischemic cerebrovascular disease events in elderly women (n=1226). METHODS: Vegetable nitrate intake, lifestyle factors, and cardiovascular disease risk factors were determined at baseline (1998). CCA-IMT and plaque severity were measured using B-mode carotid ultrasound (2001). Complete ischemic cerebrovascular disease hospitalizations or deaths (events) over 14.5 years (15 032 person-years of follow-up) were obtained from the West Australian Data Linkage System. RESULTS: Higher vegetable nitrate intake was associated with a lower maximum CCA-IMT (B=-0.015, P=0.002) and lower mean CCA-IMT (B=-0.012, P=0.006). This relationship remained significant after adjustment for lifestyle and cardiovascular risk factors (P≤0.01). Vegetable nitrate intake was not a predictor of plaque severity. In total 186 (15%) women experienced an ischemic cerebrovascular disease event. For every 1 SD (29 mg/d) higher intake of vegetable nitrate, there was an associated 17% lower risk of 14.5-year ischemic cerebrovascular disease events in both unadjusted and fully adjusted models (P=0.02). CONCLUSIONS: Independent of other risk factors, higher vegetable nitrate was associated with a lower CCA-IMT and a lower risk of an ischemic cerebrovascular disease event.

Abdominal Aortic Calcification Identified on Lateral Spine Images From Bone Densitometers Are a Marker of Generalized Atherosclerosis in Elderly Women.

OBJECTIVE: Dual-energy x-ray absorptiometry is a low-cost, minimal radiation technique used to improve fracture prediction. Dual-energy x-ray absorptiometry machines can also capture single-energy lateral spine images, and abdominal aortic calcification (AAC) is commonly seen on these images. APPROACH AND RESULTS: We investigated whether dual-energy x-ray absorptiometry-derived measures of AAC were related to an established test of generalized atherosclerosis in 892 elderly white women aged >70 years with images captured during bone density testing in 1998/1999 and B-mode carotid ultrasound in 2001. AAC scores were calculated using a validated 24-point scale into low (AAC24 score, 0 or 1), moderate (AAC24 scores, 2-5), and severe AAC (AAC24 scores, >5) seen in 45%, 36%, and 19%, respectively. AAC24 scores were correlated with mean and maximum common carotid artery intimal medial thickness (rs=0.12, P<0.001 and rs=0.14, P<0.001). Compared with individuals with low AAC, those with moderate or severe calcification were more likely to have carotid atherosclerotic plaque (adjusted prevalence ratio (PR), 1.35; 95% confidence interval, 1.14-1.61; P<0.001 and prevalence ratio, 1.94; 95% confidence interval, 1.65-2.32; P<0.001, respectively) and moderate carotid stenosis (adjusted prevalence ratio, 2.22; 95% confidence interval, 1.39-3.54; P=0.001 and adjusted prevalence ratio, 4.82; 95% confidence interval, 3.09-7.050; P<0.001, respectively). The addition of AAC24 scores to traditional risk factors improved identification of women with carotid atherosclerosis as quantified by C-statistic (+0.075, P<0.001), net reclassification (0.249, P<0.001), and integrated discrimination (0.065, P<0.001). CONCLUSIONS: AAC identified on images from a dual-energy x-ray absorptiometry machine were strongly related to carotid ultrasound measures of atherosclerosis. This low-cost, minimal radiation technique used widely for osteoporosis screening is a promising marker of generalized extracoronary atherosclerosis.

Dietary inflammatory index in relation to sub-clinical atherosclerosis and atherosclerotic vascular disease mortality in older women.

Arterial wall thickening, stimulated by low-grade systemic inflammation, underlies many cardiovascular events. As diet is a significant moderator of systemic inflammation, the dietary inflammatory index (DIITM) has recently been devised to assess the overall inflammatory potential of an individual's diet. The primary objective of this study was to assess the association of the DII with common carotid artery-intima-media thickness (CCA-IMT) and carotid plaques. To substantiate the clinical importance of these findings we assessed the relationship of DII score with atherosclerotic vascular disease (ASVD)-related mortality, ischaemic cerebrovascular disease (CVA)-related mortality and ischaemic heart disease (IHD)-related mortality more. The study was conducted in Western Australian women aged over 70 years (n 1304). Dietary data derived from a validated FFQ (completed at baseline) were used to calculate a DII score for each individual. In multivariable-adjusted models, DII scores were associated with sub-clinical atherosclerosis: a 1 sd (2·13 units) higher DII score was associated with a 0·013-mm higher mean CCA-IMT (P=0·016) and a 0·016-mm higher maximum CCA-IMT (P=0·008), measured at 36 months. No relationship was seen between DII score and carotid plaque severity. There were 269 deaths during follow-up. High DII scores were positively associated with ASVD-related death (per sd, hazard ratio (HR): 1·36; 95 % CI 1·15, 1·60), CVA-related death (per sd, HR: 1·30; 95 % CI 1·00, 1·69) and IHD-related death (per sd, HR: 1·40; 95 % CI 1·13, 1·75). These results support the hypothesis that a pro-inflammatory diet increases systemic inflammation leading to development and progression of atherosclerosis and eventual ASVD-related death.

Myocardial infarction, patient decision delay and help-seeking behaviour: a thematic analysis.

AIMS AND OBJECTIVES: To explore patient decision delay, the symptom experience and factors that motivated the patient experiencing myocardial infarction to go to the emergency department. BACKGROUND: Reperfusion for myocardial infarction is more effective if performed as soon as possible after the onset of symptoms. Multiple studies show that prehospital delay is long and can average several hours. DESIGN: A qualitative descriptive design using semi-structured interviews. METHODS: All consecutive myocardial infarction patients who between July 2013-January 2014 at a single-centre metropolitan tertiary hospital in Western Australia were included. Patient responses to an open-ended question were recorded and transcribed verbatim. Data were analysed using Braun & Clarke (Qual Res Psychol, 3, 2006, 77-101) thematic analysis method. RESULTS: Of the 367 eligible, 255 provided consent. Three themes emerged from the qualitative analyses: (1) onset and response to symptoms, and this included three subthemes: context of the event, diversity of symptom interpretation and response to symptoms; (2) help-seeking behaviour, and this included the patient seeking help from various lay and professional sources; and (3) help-seeking outcomes, which include calling the emergency ambulance, going to emergency department, seeing a general practitioner, seeing a general practitioner who advised them to go home. CONCLUSION: The context of the event, their symptomatology and the layperson who was the first point of contact influenced the decision for the patient to go to the emergency department. Many patients used private transport or contacted their general practitioner. New knowledge from this study emphasises the importance of the layperson understanding the appropriate response is to seek prompt care through immediate emergency transport by ambulance to emergency department. RELEVANCE TO CLINICAL PRACTICE: This study highlights the need to educate both the patient and the wider public, not only to seek prompt care but to also to call the emergency ambulance to arrange transport to the emergency department.

Improving Guideline Compliance in Australia With a National Percutaneous Coronary Intervention Outcomes Registry.

BACKGROUND: Secondary prevention strategies after percutaneous coronary intervention (PCI) include statins and dual anti-platelet therapy, however there are significant gaps between guidelines and practice. Contemporary PCI practice requires comprehensive data collection to allow dynamic auditing and benchmarking of key performance and safety indices. Genesis HeartCare is Australia's largest collaborative venture of cardiologists, practising at over 40 public and private hospitals. We hypothesised that measurement and local reporting of data would improve patient outcomes through improving compliance with guideline therapies. METHODS: Real-time benchmarking via a national clinical quality and outcomes register, the Genesis Cardiovascular Outcomes Registry (GCOR-PCI). GCOR-PCI prospectively collected clinical, procedural, medication and outcomes data for 6720 consecutive patients undergoing PCI from 10 private hospitals across Australia. Key performance outcomes benchmarked against the aggregated study cohort and international standards were reported to individual sites. The main outcome measure was compliance with guideline medications (statins, anti-platelet agents). RESULTS: Early data identified specific practice patterns associated with lower rates of statin therapy post-PCI, which led to changes in practice. Between the first and latest year of data collection there was significant improvement in the rates of statin therapy at discharge (92.1 vs. 94.4% p<0.03) and 12 months post-PCI (87.0 vs. 92.2% p<0.001) and of antiplatelet therapy at 12 months (90.7 vs. 94.3% p<0.001). CONCLUSIONS: This large-scale collaboration provides a platform for the development of quality improvement initiatives. Establishment of this clinical quality registry improved patient care by identifying and monitoring gaps in delivery of appropriate therapies, driving key practice change.