Monoclonal antibodies, gene silencing and gene editing (CRISPR) therapies for the treatment of hyperlipidemia-The future is here

Hyperlipidemia is a significant risk factor for atherosclerotic cardiovascular disease. Undertreatment of elevated lipids persists despite existing therapies. Here, we provide an update on monoclonal antibodies, gene silencing therapies, and gene editing techniques for the management of hyperlipidemia. The current era of cutting-edge pharmaceuticals targeting low density lipoprotein cholesterol, PCSK9, lipoprotein (a), angiopoietin-like 3, and apolipoprotein C3 are reviewed. We outline what is known, studies in progress, and futuristic goals. This review of available and upcoming biotechnological lipid therapies is presented for clinicians managing patients with familial hyperlipidemia, statin intolerance, hypertriglyceridemia, or elevated lipoprotein (a) levels

Potential implications of coronary artery calcium testing for guiding aspirin use among asymptomatic individuals with diabetes.

ObjectiveIt is unclear whether coronary artery calcium (CAC) is effective for risk stratifying patients with diabetes in whom treatment decisions are uncertain.Research design and methodsOf 44,052 asymptomatic individuals referred for CAC testing, we studied 2,384 individuals with diabetes. Subjects were followed for a mean of 5.6 ± 2.6 years for the end point of all-cause mortality.ResultsThere were 162 deaths (6.8%) in the population. CAC was a strong predictor of mortality across age-groups (age <50, 50-59, ≥60), sex, and risk factor burden (0 vs. ≥1 additional risk factor). In individuals without a clear indication for aspirin per current guidelines, CAC stratified risk, identifying patients above and below the 10% risk threshold of presumed aspirin benefit.ConclusionsCAC can help risk stratify individuals with diabetes and may aid in selection of patients who may benefit from therapies such as low-dose aspirin for primary prevention

Frequency of Disc Degeneration at Different Levels of Cervical Vertebrae in Adult Patients with Neck Pain on Magnetic Resonance Imaging

Background:Disc degeneration is terminology used for heterogeneous changes affecting the anatomy and physiology of the intervertebral disc. Disc degeneration alters the material properties of the intervertebral disc leading to an unfavorable distribution and transmission of stress to adjacent spinal structures.Objective:The aim of the study was to determine the frequency of disc degeneration at different level of cervical vertebrae in adult patients with neck pain on magnetic resonance imaging.Methodology:In this descriptive study 180 adult patients were included. All patients had been collected from DHQ hospital Gilgit and Ghurki Trust teaching hospital. After informed consent, data were collected through 1.5 tesla GE (closed bore) and 0.35 tesla Hitachi (open bore) MRI machines.Results:Findings show that among 180 adult patients, 136 presented with disc degeneration among which 81 were males and 55 were females. Among 81 males, 63 had disc degeneration at multiple levels while 18 had single disc degeneration. In females 35 patients showed multiple disc degeneration while 20 involved a single disc.Conclusion:It is concluded that disc degeneration is prevalent in males than females. Disc degeneration at multiple levels is higher than single disc degeneration in both genders. Keywords: Disc degeneration, magnetic resonance imaging, intervertebral disc. DOI: 10.7176/JHMN/71-02 Publication date: February 29th 202

Role of A20 in cIAP-2 Protection against Tumor Necrosis Factor α (TNF-α)-Mediated Apoptosis in Endothelial Cells

Tumor necrosis factor α (TNF-α) influences endothelial cell viability by altering the regulatory molecules involved in induction or suppression of apoptosis. However, the underlying mechanisms are still not completely understood. In this study, we demonstrated that A20 (also known as TNFAIP3, tumor necrosis factor α-induced protein 3, and an anti-apoptotic protein) regulates the inhibitor of apoptosis protein-2 (cIAP-2) expression upon TNF-α induction in endothelial cells. Inhibition of A20 expression by its siRNA resulted in attenuating expression of TNF-α-induced cIAP-2, yet not cIAP-1 or XIAP. A20-induced cIAP-2 expression can be blocked by the inhibition of phosphatidyl inositol-3 kinase (PI3-K), but not nuclear factor (NF)-κB, while concomitantly increasing the number of endothelial apoptotic cells and caspase 3 activation. Moreover, TNF-α-mediated induction of apoptosis was enhanced by A20 inhibition, which could be rescued by cIAP-2. Taken together, these results identify A20 as a cytoprotective factor involved in cIAP-2 inhibitory pathway of TNF-α-induced apoptosis. This is consistent with the idea that endothelial cell viability is dependent on interactions between inducers and suppressors of apoptosis, susceptible to modulation by TNF-α

Sex Differences in the Association Between Cumulative Use of Cannabis and Cognitive Function in Middle Age: The Coronary Artery Risk Development in Young Adults Study.

Background: Cannabis use may impair cognitive function (CF) differently in men and women, due to sex-specific differences in neurobiological mechanisms and environmental risk factors. Objective: Assess sex differences in the association between cumulative exposure to cannabis and cognitive performance in middle age. Methods: We studied participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, including Black and White men and women 18-30 years old at baseline followed over 30 years. Our cross-sectional analysis of CF scores at year 30 was stratified by sex. We computed categories of cumulative exposure in "cannabis-years" (1 cannabis-year=365 days of use) from self-reported use every 2 to 5 years over 30 years. At years 25 and 30, we assessed CF with the Rey Auditory Verbal Learning Test (verbal memory), the Digit Symbol Substitution Test (processing speed), and the Stroop Interference Test (executive function). At year 30, additional measures included Category and Letter Fluency Test (verbal ability) and the Montreal Cognitive Assessment (global cognition). We computed standardized scores for each cognitive test and applied multivariable adjusted linear regression models for self-reported cumulative cannabis use, excluding participants who used cannabis within 24 h. In a secondary analysis, we examined the association between changes in current cannabis use and changes in CF between years 25 and 30. Results: By year 30, 1,352 men and 1,793 women had measures of CF; 87% (N=1,171) men and 84% (N=1,502) women reported ever cannabis use. Men had a mean cumulative use of 2.57 cannabis-years and women 1.29 cannabis-years. Self-reported cumulative cannabis use was associated with worse verbal memory in men (e.g., -0.49 standardized units [SU] for ≥5 cannabis-years of exposure; 95% CI=-0.76 to -0.23), but not in women (SU=0.02; 95% CI=-0.26 to 0.29). Other measures of CF were not associated with cannabis. Changes in current cannabis use between years 25 and 30 were not associated with CF in men or women. Conclusions: Self-reported cumulative cannabis exposure was associated with worse verbal memory in men but not in women. Researchers should consider stratified analyses by sex when testing the association between cannabis and cognition

Resting Heart Rate and Metabolic Syndrome in Patients With Diabetes and Coronary Artery Disease in Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial

The relation between the metabolic syndrome (MetS) and resting heart rate (rHR) in patients with diabetes and coronary artery disease is unknown. The authors examined the cross-sectional association at baseline between components of the MetS and rHR and between rHR and left ventricular ejection fraction in the population from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized clinical trial. The mean rHR in the MetS group was significantly higher than in those without (68.4±12.3 vs 65.6±11.8 beats per min, P=.0017). The rHR was higher (P<.001 for trend) with increasing number of components for MetS. Linear regression analyses demonstrated that as compared to individuals without MetS, rHR was significantly higher in participants with MetS (regression coefficient, 2.9; P=.0015). In patients with type 2 diabetes and coronary artery disease, the presence of higher rHR is associated with increasing number of criteria of MetS and the presence of ventricular dysfunction.Prev Cardiol. 2010;13:112–116. © 2009 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79383/1/j.1751-7141.2010.00067.x.pd

Closing the gaps in care of dyslipidemia: Revolutionizing management with digital health and innovative care models

Although great progress has been made in the diagnostic and treatment options for dyslipidemias, unawareness, underdiagnosis and undertreatment of these disorders remain a significant global health concern. Growth in digital applications and newer models of care provide novel tools to improve the management of chronic conditions such as dyslipidemia. In this review, we discuss the evolving landscape of lipid management in the 21st century, current treatment gaps and possible solutions through digital health and new models of care. Our discussion begins with the history and development of value-based care and the national establishment of quality metrics for various chronic conditions. These concepts on the level of healthcare policy not only inform reimbursements but also define the standard of care. Next, we consider the advances in atherosclerotic cardiovascular disease risk score calculators as well as evolving imaging modalities. The impact and growth of digital health, ranging from telehealth visits to online platforms and mobile applications, will also be explored. We then evaluate the ways in which machine learning and artificial intelligence-driven algorithms are being utilized to address gaps in lipid management. From an organizational perspective, we trace the redesign of medical practices to incorporate a multidisciplinary team model of care, recognizing that atherosclerotic cardiovascular disease risk is multifaceted and requires a comprehensive approach. Finally, we anticipate the future of dyslipidemia management, assessing the many ways in which atherosclerotic cardiovascular disease burden can be reduced on a population-wide scale

Association Between Modifiable Risk Factors and Pharmaceutical Expenditures Among Adults With Atherosclerotic Cardiovascular Disease in the United States: 2012–2013 Medical Expenditures Panel Survey

Background Atherosclerotic cardiovascular disease (ASCVD) causes most deaths in the United States and accounts for the highest healthcare spending. The association between the modifiable risk factors (MRFs) of ASCVD and pharmaceutical expenditures are largely unknown. Methods and Results We examined the association between MRFs and pharmaceutical expenditures among adults with ASCVD using the 2012 and 2013 Medical Expenditure Panel Survey. A 2‐part model was used while accounting for the survey\u27s complex design to obtain nationally representative results. All costs were adjusted to 2013 US dollars using the gross domestic product deflator. The annual total pharmaceutical expenditure among those with ASCVD was $71.6 billion, 33$519 [95% confidence interval (CI), $12–918; P=0.011]), dyslipidemia ($631 [95% CI, $168–1094; P=0.008]), hypertension: ($1078 [95% CI, $697–1460; P\u3c0.001)], and diabetes mellitus ($2006 [95% CI, $1470–2542]). Compared with those with optimal MRFs (0–1), those with average MRFs (2–3) spent an average of$1184 (95% CI, $805–1564; P\u3c0.001) more on medications, and those with poor MRFs (≥4) spent$2823 (95% CI, $2338–3307; P\u3c0.001) more. Conclusions Worsening MRFs were proportionally associated with higher annual pharmaceutical expenditures among patients with established ASCVD regardless of non‐ASCVD comorbidity. In‐depth studies of the roles played by other factors in this association can help reduce medication‐related expenditures among ASCVD patients