Although common APOE genetic variation has a major influence on plasma LDL-cholesterol, its role in affecting HDL-cholesterol and triglycerides is not well established. Recent genome-wide association studies suggest that APOE also affects plasma variation in HDL-cholesterol and triglycerides. It is thus important to resequence the APOE gene to identify both common and uncommon variants that affect plasma lipid profile. Here, we have sequenced the APOE gene in 190 subjects with extreme HDL-cholesterol levels selected from two well-defined epidemiological samples of U.S. non-Hispanic Whites (NHWs) and African Blacks followed by genotyping of identified variants in the entire datasets (623 NHWs, 788 African Blacks) and association analyses with major lipid traits. We identified a total of 40 sequence variants, of which 10 are novel. A total of 32 variants, including common tagSNPs (≥5% frequency) and all uncommon variants (<5% frequency) were successfully genotyped and considered for genotype-phenotype associations. Other than the established associations of APOE*2 and APOE*4 with LDL-cholesterol, we have identified additional independent associations with LDL-cholesterol. We have also identified multiple associations of uncommon and common APOE variants with HDL-cholesterol and triglycerides. Our comprehensive sequencing and genotype-phenotype analyses indicate that APOE genetic variation impacts HDL-cholesterol and triglycerides in addition to affecting LDL-cholesterol.

The autonomic nervous system plays a key role in regulating changes in the cardiovascular system and its adaptation to various human body functions. The sympathetic arm of the autonomic nervous system is associated with the fight and flight response, while the parasympathetic division is responsible for the restorative effects on heart rate, blood pressure, and contractility. Disorders involving these two divisions can lead to, and are seen as, a manifestation of most common cardiovascular disorders. Over the last few decades, extensive research has been performed establishing imaging techniques to quantify the autonomic dysfunction associated with various cardiovascular disorders. Additionally, several techniques have been tested with variable success in modulating the cardiac autonomic nervous system as treatment for these disorders. In this review, we summarize basic anatomy, physiology, and pathophysiology of the cardiac autonomic nervous system including adrenergic receptors. We have also discussed several imaging modalities available to aid in diagnosis of cardiac autonomic dysfunction and autonomic modulation techniques, including pharmacologic and device-based therapies, that have been or are being tested currently.

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There is paucity of outcomes data on patients receiving fibrinolytic therapy (FT) for acute ST-elevation myocardial infarction (STEMI) in Indo-Asians. We conducted this study to determine survival as well as correlates of mortality in this population. Hospital charts of 230 patients receiving FT for acute STEMI between January 2002 and December 2004 were reviewed. Primary outcome variable was total mortality. Cox proportional hazards regression models were constructed. At a median follow-up of 717 days, 13.5% died, majority (23) during the in-hospital period. Multivariate predictors of mortality included (adjusted hazards ratio [HR], 95% confidence interval [CI]) age (HR 1.06, 95% CI 1.01-1.13), ejection fraction (HR 0.93, 95% CI 0.89-0.97), admission white cell count (HR 1.02, 95% CI 1.01-1.04) and change in ST-segment elevation (HR 0.96, 95% CI 0.92-0.99). We conclude that patients receiving FT for acute STEMI in Pakistan are a relatively high-risk group with a 10% in-hospital mortality and high frequency of recurrent events. Comparison data with primary angioplasty as an alternative strategy are needed.

Despite being one of the most prevalent cardiac arrhythmias, the cause of atrial fibrillation (AF) in a vast majority of patients remains unknown. There is growing evidence of associated AF in patients diagnosed with coronary arteriovenous fistula. In this discussion, we have included an example of a patient who presented with new-onset AF and was subsequently diagnosed with an anomalous fistula between the right coronary artery and the superior vena cava. Definitive treatment of the fistula resulted in permanent resolution of the AF. Based on this case and a similar case reported in the literature, it is proposed that further research will unmask this possibly underdiagnosed and very treatable cause of AF.

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