Personalized vascular medicine: Individualizing drug therapy

deGoma, Emil M.; Rivera, Giovanni; Lilly, Scott; Usman, Muhammad; Mohler, Emile R.

doi:10.1177/1358863x11422251

Cited by 20 publications

(14 citation statements)

References 119 publications

(147 reference statements)

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“…There are two different interpretations to Figs 7 and 8: 1) the genetic variant predicts the change in postprandial lipemia (personalized medicine perspective represented by the histograms), and 2) postprandial triglyceride concentrations predict the effect size of the genetic variant (quantile-dependent expressivity). Whereas, some advocate individualized drug prescriptions through the use of genetic markers to identify patients most likely to benefit from fenofibrate treatment [138], quantile-dependent Quantile-dependent expressivity of postprandial lipemia expressivity postulates that the results represent a basic phenomenon where the genetic effect size increases with plasma triglyceride concentration.…”

Section: Fenofibrate Treatmentmentioning

confidence: 99%

Quantile-dependent expressivity of postprandial lipemia

Williams

2020

PLoS ONE

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Purpose "Quantile-dependent expressivity" describes an effect of the genotype that depends upon the level of the phenotype (e.g., whether a subject's triglycerides are high or low relative to its population distribution). Prior analyses suggest that the effect of a genetic risk score (GRS) on fasting plasma triglyceride levels increases with the percentile of the triglyceride distribution. Postprandial lipemia is well suited for testing quantile-dependent expressivity because it exposes each individual's genotype to substantial increases in their plasma triglyceride concentrations. Ninety-seven published papers were identified that plotted mean triglyceride response vs. time and genotype, which were converted into quantitative data. Separately, for each published graph, standard least-squares regression analysis was used to compare the genotype differences at time t (dependent variable) to average triglyceride concentrations at time t (independent variable) to assess whether the genetic effect size increased in association with higher triglyceride concentrations and whether the phenomenon could explain purported genetic interactions with sex, diet, disease, BMI, and drugs. ResultsConsistent with the phenomenon, genetic effect sizes increased (P�0.05) with increasing triglyceride concentrations for polymorphisms associated with

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Section: Fenofibrate Treatmentmentioning

confidence: 99%

Quantile-dependent expressivity of postprandial lipemia

Williams

2020

PLoS ONE

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“…Prediction of the rate of progression will not only help in stratification of patients according to risk of ESRD but will also direct development/selection of specific therapies to prevent or delay the onset of ESRD. Such personalized approaches are being developed in other fields [54-56]. …”

Section: Progressive Renal Decline and Considerations For Therapeuticmentioning

confidence: 99%

Progressive renal decline as the major feature of diabetic nephropathy in type 1 diabetes

2013

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Despite almost universal implementation of reno-protective therapies over the last 25 years, risk of ESRD in type 1 diabetes (T1D) is not decreasing, and ESRD remains the major cause of excess morbidity and premature mortality [1]. Such a state of affairs prompts a call to action. In this review we re-evaluated the proteinuria-centric model of diabetic nephropathy and showed its deficiencies. On the basis of the extensive studies that we have been conducting in the population of the Joslin Clinic, we propose that progressive renal decline, not abnormalities in urinary albumin excretion, should be considered as the major feature of disease processes leading to ESRD in T1D. Etiology of diabetic nephropathy should be reconsidered in light of our new findings so our perspective can be broadened regarding new therapeutic targets available for interrupting the progressive renal decline in T1D. Reduction in the rate of GFR loss, not reduction of AER, should become the measure for evaluating the effectiveness of new therapeutic interventions. We need new accurate methods for early diagnosis of patients at risk of progressive renal decline or, better yet, for detecting in advance which patients will have rapid, moderate or minimal rate of progression to ESRD.

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“…A study by Degoma et al59) reviewed and classified four major pharmacotherapeutic drugs within vascular medicine; antiplatelet therapy {platelet aggregation assay (VeryfyNow® PRA-100), cytochrome P450 2C19 genotype, paraoxonase I genotype}, antihypertensive therapy (plasma rennin activity, bradykinin type I receptor haplotype, angiotensin II type I receptor haplotype), lipid-lowering therapy (solute carrier organic anion transporter family, member IBI genotype, apolipoprotein A5 genotype, Niemann-Pick C1 Like 1 haplotype), and antithrombotic therapy {cytochrome P450 2C9 (CYP2C9) genotype, vitamin K epoxide reductase complex genotype}.…”

Section: Personalized Medicine In Cardiovascular Diseases By Human Gementioning

confidence: 99%

Personalized Medicine in Cardiovascular Diseases

et al. 2012

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Personalized medicine is a novel medical model with all decisions and practices being tailored to individual patients in whatever ways possible. In the era of genomics, personalized medicine combines the genetic information for additional benefit in preventive and therapeutic strategies. Personalized medicine may allow the physician to provide a better therapy for patients in terms of efficiency, safety and treatment length to reduce the associated costs. There was a remarkable growth in scientific publication on personalized medicine within the past few years in the cardiovascular field. However, so far, only very few cardiologists in the USA are incorporating personalized medicine into clinical treatment. We review the concepts, strengths, limitations and challenges of personalized medicine with a particular focus on cardiovascular diseases (CVDs). There are many challenges from both scientific and policy perspectives to personalized medicine, which can overcome them by comprehensive concept and understanding, clinical application, and evidence based practices. Individualized medicine serves a pivotal role in the evolution of national and global healthcare reform, especially, in the CVDs fields. Ultimately, personalized medicine will affect the entire landscape of health care system in the near future.

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Personalized vascular medicine: Individualizing drug therapy

Cited by 20 publications

References 119 publications

Quantile-dependent expressivity of postprandial lipemia

Quantile-dependent expressivity of postprandial lipemia

Progressive renal decline as the major feature of diabetic nephropathy in type 1 diabetes

Personalized Medicine in Cardiovascular Diseases

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