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Biomedical subjects

Alawi A Alsheikh-Ali

Publications and source records attributed to Alawi A Alsheikh-Ali.

13 recordsLinked to original sources
PubMed2026

HPRC2: A human pangenome reference with near-complete coverage of common genetic variation.

A pangenome reference overcomes the inherent limitation of any individual reference genome by integrating the variation present in a population. We present the Human Pangenome Reference Consortium's (HPRC) Release 2 (HPRC2), an openly available, second phase pangenome that is an approximately fivefold expansion in genome number over HPRC Release 1 (HPRC1) and measurable improvement in genome completeness, contiguity, and accuracy. Selecting samples with a principled algorithm prioritising common variant coverage, HPRC2 contributes 460 haplotypes that together capture over 99% of common variation observed in the All of Us Research Program v8 cohort. Combining high-coverage long and ultra-long reads with modern assemblers and polishers, we produce thousands of telomere-to-telomere (T2T) chromosomes, and relative to HPRC1 halve the number of structurally unreliable regions as well as individual base errors per haplotype. We complement the assemblies with whole genome multiple alignments and gene annotations, and derive formal pangenome coordinate systems for addressing off-reference variation, demonstrating that individual human genomes contain more than one hundred thousand variants not succinctly described with respect to existing reference genomes. We also present the first matched long-read backed pantranscriptome and panepigenome at this scale, provide continuous local-ancestry estimates spanning every genome, and outline a host of new tools and applications that leverage the pangenome resource for improved genomics analysis.

Journal Article↗
PubMed2006

Extent to which accepted serum lipid goals are achieved in a contemporary general medical population with coronary heart disease risk equivalents.

This study examined lipid levels and the use of lipid-altering drugs in a contemporary general medical population without documented coronary heart disease (CHD) but with CHD risk equivalents. On the basis of present national guidelines, the following lipid values (in milligrams per deciliter) were considered optimal for this population: low-density lipoprotein cholesterol <100, high-density lipoprotein (HDL) cholesterol >or=40 in men and >or=50 in women, and non-HDL cholesterol <130 if triglycerides are >or=200. Of 44,052 active patients screened, 877 with CHD risk equivalents as defined by the Adult Treatment Panel III guidelines were identified. Most patients did not meet optimal lipid targets for low-density lipoprotein cholesterol (59%), HDL cholesterol (66%), and non-HDL cholesterol (72%). Indeed, 88% of patients did not meet >or=1 lipid goal. Statins were used in 57% of patients. In patients with low HDL cholesterol, only 4.7% were taking niacin and 4.9% fibrates. In the subgroup of patients with triglycerides >or=200 mg/dl, only 9.5% were taking fibrates and 8.2% niacin. In conclusion, the present analysis highlights the dramatic need to further improve preventive measures in a substantial proportion of high-risk patients with CHD risk equivalents.

Aged↗
PubMed2006

High-density lipoprotein cholesterol-raising strategies.

There is a distinct inverse relationship between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease risk. HDL-C mediates cholesterol efflux from the vasculature and promotes anti-oxidant, anti-inflammatory, and anti-thrombotic effects. There are multiple lifestyle and therapeutic interventions that raise HDL-C, and there is increasing evidence that these interventions improve cardiovascular outcomes. Recent findings regarding the role of HDL-C in cholesterol metabolism offer new strategies designed to target atherosclerosis. This review highlights the utility of existing HDL-C-raising strategies and examines new potential therapies.

Apolipoprotein A-I↗
PubMed2006

The renin-angiotensin system: a therapeutic target in atrial fibrillation.

There is growing evidence to suggest a role for the renin-angiotensin system (RAS) in the pathogenesis of atrial fibrillation (AF). Experimental animal data suggest RAS-dependent mechanisms for the development of a structural and electrophysiologic substrate for AF. This is consistent with clinical data demonstrating the effectiveness of RAS blockade in preventing new-onset or recurrent AF in a variety of patient populations including patients with hypertension and left ventricular hypertrophy, congestive heart failure, and those undergoing electrical cardioversion for AF. This review summarizes experimental and clinical evidence to date relating to the role of RAS in the pathogenesis of AF, and the efficacy of its inhibition in managing this common arrhythmia.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Evaluation of peripheral vascular endothelial function with a portable ultrasound device.

Endothelial function can be assessed noninvasively by imaging the brachial artery with ultrasound before and during reactive hyperemia. However, the standard ultrasound equipment typically used for this purpose is limited by size and expense of the machinery. In this study, we compared the ability of a portable ultrasound device to standard ultrasound equipment to visualize the brachial artery for purposes of assessing peripheral vascular endothelial function. The portable device provided comparable imaging of the brachial artery at rest and during hyperemia to that of standard ultrasound technology. These findings support the feasibility of noninvasive evaluation of peripheral endothelial function in the ambulatory setting.

Adult↗
PubMed2005

The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis.

BACKGROUND: Statins are currently the mainstay of dyslipidemia management for the primary and secondary prevention of cardiovascular disease. Controversial concerns about the safety of the newly marketed statin rosuvastatin have been raised on the basis of premarketing studies and a few postmarketing reports. METHODS AND RESULTS: We reviewed rosuvastatin-associated adverse events reported to the US Food and Drug Administration over its first year of marketing. On the basis of prescription data obtained from IMS Health, rates of adverse event reports (AERs) per million prescriptions were calculated. Rates of rosuvastatin-associated AERs over its first year of marketing were compared with those seen with atorvastatin, simvastatin, and pravastatin over the concurrent timeframe and during their respective first years of marketing. Comparison was also made to the first year of marketing of cerivastatin. The primary analysis examined the composite end point of AERs of rhabdomyolysis, proteinuria, nephropathy, or renal failure. With either timeframe comparison, rosuvastatin was significantly more likely to be associated with the composite end point of rhabdomyolysis, proteinuria, nephropathy, or renal failure AERs. Reported cases of rhabdomyolysis, proteinuria, or renal failure tended to occur early after the initiation of therapy and at relatively modest doses of rosuvastatin. The increased rate of rosuvastatin-associated AERs relative to other widely used statins was also observed in secondary analyses when other categories of AERs were examined, including adverse events with serious outcomes, liver toxicity, and muscle toxicity without rhabdomyolysis. CONCLUSIONS: The present analysis supports concerns about the relative safety of rosuvastatin at the range of doses used in common clinical practice in the general population.

Consumer Product Safety↗
PubMed2005

High-density lipoprotein cholesterol in the cardiovascular equation: does the "good" still count?

This article will discuss our current understanding of the role of HDL-C in the statin era, focusing on the question as to whether HDL-C still "counts" when determining cardiovascular risk. Epidemiologic evidence consistently demonstrates that low HDL-C is a strong and independent risk factor for CHD. The epidemiologic evidence is complimented by clinical data showing that interventions that raise HDL-C are associated with reductions in CHD risk, as well as by a growing body of experimental data demonstrating biologically plausible mechanisms that may underlie the observed clinical findings. Analyses of large statin trials also indicate that the significant and independent relationship between HDL-C and CHD risk persists despite the therapeutic effects of statins, and that HDL-C levels in statin-treated patients, both at baseline and in response to statin therapy, are relevant. Early studies on novel HDL targeting therapies are promising, but their long term safety profile and impact on clinical outcomes is yet to be determined in larger studies. Recent guidelines emphasize low HDL-C as an independent risk factor for cardiovascular disease, specifically identify HDL-C as a target for intervention, and encourage the use of HDL-C raising interventions in high-risk patients with low HDL-C levels.

Cardiovascular Diseases↗
PubMed2005

Adverse events with concomitant amiodarone and statin therapy.

The authors reviewed adverse events (AEs) reported to the United States Food and Drug Administration to determine the percentage of statin-associated AE reports with concurrent amiodarone use for simvastatin, atorvastatin, and pravastatin. AEs affecting the following organ systems were analyzed: muscle, liver, pancreas, and bone marrow. The percentage of simvastatin reports with concurrent amiodarone use was 1.0%, compared with 0.7% of the atorvastatin-associated reports (p = not significant). The percentage of pravastatin reports with concurrent amiodarone use was 0.4% (p < 0.05 for pravastatin vs. simvastatin). Muscle toxicity was the most commonly reported statin-amiodarone AE, accounting for 77% of the reports. AEs tended to occur in older male patients (mean age, 76 years), who were on multiple other medications (mean number of other medications, five). Clinicians should be vigilant about muscle-related complaints in patients concomitantly taking amiodarone, especially in elderly patients on multiple medications. Use of a statin not metabolized through the cytochrome P450-3A4 system may be appropriate in this setting.

Adverse Drug Reaction Reporting Systems↗
PubMed2004

Risk of adverse events with fibrates.

An increased risk for adverse events was observed with gemfibrozil relative to fenofibrate, predominantly driven by an increased rate of rhabdomyolysis. This difference was especially noticeable in patients taking the combination of gemfibrozil and a statin, particularly cerivastatin.

Aged↗
PubMed2004

Enalapril treatment and hospitalization with atrial tachyarrhythmias in patients with left ventricular dysfunction.

BACKGROUND: Experimental and clinical evidence suggests a preventive role for agiotensin-coverting enzyme (ACE) inhibitors on the development of atrial fibrillation. However, the effect of ACE inhibition on hospitalization with atrial tachyarrhythmias in patients with left ventricular (LV) dysfunction is not known. We sought to determine whether enalapril treatment reduced hospitalizations with atrial tachyarrhythmias in patients with LV dysfunction. METHODS: We performed a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) trial. Hospitalizations with atrial tachyarrhythmias were noted. RESULTS: A total of 192 hospitalizations with atrial tachyarrhythmias occurred in 158 patients during a follow-up period of 34 months. The time to first hospitalization with atrial tachyarrhythmias or death was significantly lower in the enalapril group (P =.005). In a multivariate analysis adjusting for the presence of atrial fibrillation at study entry, enalapril treatment was associated with a reduction in the rate of hospitalization with atrial tachyarrhythmias or death (RR, 0.87; 95% CI, 0.79-0.96; P =.007). The incidence of hospitalization with atrial tachyarrhythmias was 7.9 hospitalizations per 1000 patient-years of follow-up in the enalapril group, compared with 12.4 per 1000 patient-years in the placebo group (RR, 0.64; 95% CI, 0.48-0.85; P =.002). CONCLUSION: Enalapril is associated with a decreased incidence of hospitalization with atrial tachyarrhythmias in patients with LV dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗