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Use of pharmacogenomics in elderly patients treated for cardiovascular diseases.

ABSTRACT: Older people are increasingly susceptible to adverse drug reactions (ADRs) or therapeutic failure. This could be mediated by considerable polypharmacy, which increases the possibility of drug-drug and drug-gene interactions. Precision medicine, based on individual genetic variations, enables the screening of patients at risk for ADRs and the implementation of personalized treatment regimens. It combines genetic and genomic data with environmental and clinical factors in order to tailor prevention and disease-management strategies, including pharmacotherapy. The identification of genetic factors that influence drug absorption, distribution, metabolism, excretion, and action at the drug target level allows individualized therapy. Positive pharmacogenomic findings have been reported for the majority of cardiovascular drugs (CVD), suggesting that pre-emptive testing can improve efficacy and minimize the toxicity risk. Gene variants related to drug metabolism and transport variability or pharmacodynamics of major CVD have been translated into dosing recommendations. Pharmacogenetics consortia have issued guidelines for oral anticoagulants, antiplatelet agents, statins, and some beta-blockers. Since the majority of pharmacogenetics recommendations are based on the assessment of single drug-gene interactions, it is imperative to develop tools for the prediction of multiple drug-drug-gene interactions, which are common in the elderly with comorbidity. The availability of genomic testing has grown, but its clinical application is still insufficient.

SUBMITTER: Bozina N

PROVIDER: S-EPMC7230415 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Use of pharmacogenomics in elderly patients treated for cardiovascular diseases.

Božina Nada N Vrkić Kirhmajer Majda M Šimičević Livija L Ganoci Lana L Mirošević Skvrce Nikica N Klarica Domjanović Iva I Merćep Iveta I

Croatian medical journal 20200401 2

Older people are increasingly susceptible to adverse drug reactions (ADRs) or therapeutic failure. This could be mediated by considerable polypharmacy, which increases the possibility of drug-drug and drug-gene interactions. Precision medicine, based on individual genetic variations, enables the screening of patients at risk for ADRs and the implementation of personalized treatment regimens. It combines genetic and genomic data with environmental and clinical factors in order to tailor preventio ...[more]

PMID: 32378381

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Project description:The authors sought to examine the impact of multiple risk alleles for cognitive dysfunction and cardiovascular disease risk on cognitive function and to determine if these relationships varied by cognitive reserve (CR) or concomitant medication use in patients with schizophrenia. They conducted a cross-sectional study in ambulatory mental health centers. A total of 122 adults with a schizophrenia spectrum diagnosis who were maintained on a stable antipsychotic regimen for at least 6 months before study enrollment were included. Patients were divided into three CR groups based on years of formal education: no high school completion or equivalent (low-education group [18 patients]), completion of high school or equivalent (moderate-education group [36 patients], or any degree of post-high school education (high-education group [68 patients]). The following pharmacogenomic variants were genotyped for each patient: AGT M268T (rs699), ACE insertion/deletion (or ACE I/D, rs1799752), and APOE ε2, ε3, and ε4 (rs429358 and rs7412). Risk allele carrier status (identified per gene as AGT M268 T carriers, ACE D carriers, and APOE ε4 carriers) was not significantly different among CR groups. The Brief Assessment of Cognition in Schizophrenia (BACS) scale was used to assess cognitive function. The mean ± SD patient age was 43.9 ± 11.6 years. Cardiovascular risk factors such as hypertension and hyperlipidemia diagnoses, and use of antihypertensive and lipid-lowering agents, did not significantly differ among CR groups. Mixed modeling revealed that risk allele carrier status was significantly associated with lower verbal memory scores for ACE D and APOE ε4 carriers, but AGT T carrier status was significantly associated with higher verbal memory scores (p=0.0188, p=0.0055, and p=0.0058, respectively). These results were only significant in the low-education group. In addition, medication-gene interactions were not significant predictors of BACS scores. ACE D and APOE ε4 carrier status, independent of medication use, was associated with lower verbal memory scores in patients with schizophrenia who had relatively lower CR, as identified by formal education. These results suggest that increasing CR may be protective against cognitive impairment that may be worsened by select cardiovascular risk alleles in patients with schizophrenia.

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Dataset Information

Use of pharmacogenomics in elderly patients treated for cardiovascular diseases.

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Use of pharmacogenomics in elderly patients treated for cardiovascular diseases.

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