Genes regulating levels of ω-3 long-chain polyunsaturated fatty acids are associated with alcohol use disorder and consumption, and broader externalizing behavior in humans.

BACKGROUND: Individual variation in the physiological response to alcohol is predictive of an individual's likelihood to develop alcohol use disorder (AUD). Evidence from diverse model organisms indicates that the levels of long-chain polyunsaturated omega-3 fatty acids (ω-3 LC-PUFAs) can modulate the behavioral response to ethanol and therefore may impact the propensity to develop AUD. While most ω-3 LC-PUFAs come from diet, humans can produce these fatty acids from shorter chain precursors through a series of enzymatic steps. Natural variation in the genes encoding these enzymes has been shown to affect ω-3 LC-PUFA levels. We hypothesized that variation in these genes could contribute to the susceptibility to develop AUD. METHODS: We identified nine genes (FADS1, FADS2, FADS3, ELOVL2, GCKR, ELOVL1, ACOX1, APOE, and PPARA) that are required to generate ω-3 LC-PUFAs and/or have been shown or predicted to affect ω-3 LC-PUFA levels. Using both set-based and gene-based analyses we examined their association with AUD and two AUD-related phenotypes, alcohol consumption, and an externalizing phenotype. RESULTS: We found that the set of nine genes is associated with all three phenotypes. When examined individually, GCKR, FADS2, and ACOX1 showed significant association signals with alcohol consumption. GCKR was significantly associated with AUD. ELOVL1 and APOE were associated with externalizing. CONCLUSIONS: Taken together with observations that dietary ω-3 LC-PUFAs can affect ethanol-related phenotypes, this work suggests that these fatty acids provide a link between the environmental and genetic influences on the risk of developing AUD.

How common are non-acute coronary syndrome (ACS) diagnoses in patients with suspected ACS investigated with coronary angiography in New Zealand? (ANZACS-QI 58).

BACKGROUND AND AIMS: The last two decades in New Zealand have seen increased availability of primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) and early invasive coronary angiography (ICA) for other high-risk acute coronary syndrome (ACS) patients. One metric to assess the clinical appropriateness of these invasive strategies is to examine the false-positive rate for the investigation (ie, the rate of non-ACS diagnoses). METHODS: All patients presenting to New Zealand public hospitals with suspected ACS who underwent ICA between 2015 and 2019 were recorded prospectively in the All New Zealand Acute Coronary Syndrome Quality Improvement registry. The cohort was divided according to clinical impression at presentation: (1) suspected STEMI <24h and (2) other suspected ACS. The final discharge diagnosis for each patient were obtained from the registry. RESULTS: There were 6,059 (20%) patients with suspected STEMI <24h and 24,258 (80%) with other suspected ACS. Of the suspected STEMIs <24h, 90.6% had a final diagnosis of STEMI, 3.5% non-ST segment elevation ACS (NSTEACS) and only 5.9% had a non-ACS diagnosis. Of those with other suspected ACS, 80.7% had a final ACS diagnosis. Across all New Zealand district health boards (DHBs), the proportion of non-ACS diagnoses was similar for suspected STEMI presentations. However, for other suspected ACS, the proportions were higher in DHBs with rapid access to coronary interventional facilities than in those without (17.6% vs 7.0%, p<0.001). CONCLUSIONS: False-positive catheter laboratory activations for suspected STEMI patients are low across New Zealand. The differences in the proportion of non-ACS diagnoses according to DHB interventional capability for other suspected ACS requires further investigation.

Myocardial Infarction Without Obstructive Coronary Artery Disease is Not a Benign Condition (ANZACS-QI 10).

BACKGROUND: Non-obstructive coronary artery disease (CAD) on coronary angiography after myocardial infarction (MI) is associated with a lower risk of adverse outcomes, but the prognosis may not be benign. Our aim was to assess outcomes in MI with and without obstructive CAD, and in an age and sex matched comparison cohort without known cardiovascular disease. METHODS: We performed a single centre analysis of consecutive patients undergoing coronary angiography for MI between 2007 and 2012. Patients were classified into those with obstructive CAD (≥50% epicardial coronary artery stenosis) and those without obstructive CAD (<50%). Myocardial infarction patient data was collected in an electronic registry and linked anonymously to national hospitalisation and mortality records. Age and sex matched patients without known CVD were identified from the community PREDICT cohort. RESULTS: Of the 2070 patients with MI, 302 (15%) had non-obstructive CAD. Compared to patients with obstructive disease they were younger (mean 57 v 61 years, p<0.001), more likely to be women (50% vs 23%, p<0.001), to be of Maori or Pacific vs. European ethnicity (p<0.001), more likely to be lifelong non-smokers (46% v 38%, p=0.02), non-diabetic (80v 73%, p <0.01), have no ST-segment deviation (78% v 46%, p<0.001), and have a low risk Global Registry of Acute Coronary Events acute coronary syndrome (GRACE ACS) score (54 v 35%, p<0.001). They were also less likely to receive 'triple therapy' secondary prevention medications (81% v 94%, p<0.0001). The cumulative two-year Kaplan-Maier composite outcome of mortality or non-fatal MI was 14.3% for MI with obstructive CAD, 4.6% for MI without obstructive disease, and 2.2% for patients without prior CVD (p<0.001). CONCLUSION: Myocardial infarction without obstructive coronary disease is common (∼1 in 7 patients) and is not clinically benign, with an adverse outcome rate double that of age and sex matched patients without CVD.