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Article ; Online: Renal Dysfunction and Outcomes in Patients With ST-Elevation Myocardial Infarction Treated With Percutaneous Coronary Intervention.

Abughofah, Yousaf / Anderson, Wesley L / Kreutz, Rolf P

2024 Volume 217, Page(s) 35–38

MeSH term(s)	Humans ; ST Elevation Myocardial Infarction ; Treatment Outcome ; Risk Factors ; Percutaneous Coronary Intervention/adverse effects ; Kidney Diseases/etiology
Language	English
Publishing date	2024-02-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	80014-4
ISSN	1879-1913 ; 0002-9149
ISSN (online)	1879-1913
ISSN	0002-9149
DOI	10.1016/j.amjcard.2024.01.039
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Article ; Online: IL-1R (Interleukin-1 Receptor) Signaling and Attenuated Hepatic CYP (Cytochrome P450) 2C Expression: Explanation for Higher Rate of Clopidogrel Resistance in Patients With Diabetes Mellitus?

Kreutz, Rolf P

Arteriosclerosis, thrombosis, and vascular biology

2020 Volume 40, Issue 6, Page(s) 1429–1431

MeSH term(s)	Animals ; Clopidogrel ; Cytochrome P-450 Enzyme System ; Diabetes Mellitus ; Diet ; Disease Models, Animal ; Humans ; Mice ; Obesity ; Receptors, Interleukin-1
Chemical Substances	Receptors, Interleukin-1 ; Cytochrome P-450 Enzyme System (9035-51-2) ; Clopidogrel (A74586SNO7)
Language	English
Publishing date	2020-05-27
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.120.314446
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Article ; Online: Isolated Right Ventricular Myocardial Infarction Presenting With Anterior ST-Segment Elevation.

Mallory, Ryan / Kreutz, Rolf P

JACC. Case reports

2022 Volume 4, Issue 9, Page(s) 556–558

Abstract: Isolated right ventricular myocardial infarctions (MIs) are rare, especially those presenting with anterior ST-segment elevation, which is normally seen in anterior MI. This occurs if the right coronary artery is nondominant. Differentiating between them ...

Abstract	Isolated right ventricular myocardial infarctions (MIs) are rare, especially those presenting with anterior ST-segment elevation, which is normally seen in anterior MI. This occurs if the right coronary artery is nondominant. Differentiating between them is important for clinical management. Our case demonstrates a right ventricular MI presenting as an anterior ST-segment elevation myocardial infarction. (
Language	English
Publishing date	2022-05-04
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-0849
ISSN (online)	2666-0849
DOI	10.1016/j.jaccas.2022.03.002
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Article ; Online: Sex specific differences of factor XI and relationship with other coagulation factors.

Kreutz, Rolf P / Ipe, Joseph / Skaar, Todd C

Thrombosis research

2023 Volume 226, Page(s) 156–158

MeSH term(s)	Male ; Female ; Humans ; Factor XI ; Blood Coagulation Factors ; Fibrinogen ; Factor XII
Chemical Substances	Factor XI (9013-55-2) ; Blood Coagulation Factors ; Fibrinogen (9001-32-5) ; Factor XII (9001-30-3)
Language	English
Publishing date	2023-04-21
Publishing country	United States
Document type	Letter
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2023.04.004
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Article ; Online: Measures of social deprivation and outcomes after percutaneous coronary intervention.

Torabi, Asad J / Von der Lohe, Elisabeth / Kovacs, Richard J / Frick, Kyle A / Kreutz, Rolf P

Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions

2023 Volume 101, Issue 6, Page(s) 995–1000

Abstract: ... comorbidities and a higher risk of death [hazard ratio (HR): 1.22 (95% confidence interval, CI: 1.1-1.39, p = 0 ... 004); log rank: p = 0.009] and CHF readmission [HR: 1.56 (1.39-1.75, p < 0.001); log rank: p < 0.001 ...

Abstract	Background: Disparities in socioeconomic status are a frequently cited factor associated with worse cardiovascular outcomes. The social deprivation index (SDI) can be used to quantify socioeconomic resources at the population level. Objectives: The aim of this study was to assess the association of SDI with clinical outcomes following percutaneous coronary interventions (PCI). Methods: This was a retrospective observational analysis of patients who underwent PCI and were included in a multicenter cardiac catheterization registry study. Baseline characteristics, congestive heart failure (CHF) readmission rates and survival were compared between patients with the highest and lower SDI. SDI was calculated based on the US community survey census tract-level data. Results: Patients within the highest SDI quintile (n = 1843) had more comorbidities and a higher risk of death [hazard ratio (HR): 1.22 (95% confidence interval, CI: 1.1-1.39, p = 0.004); log rank: p = 0.009] and CHF readmission [HR: 1.56 (1.39-1.75, p < 0.001); log rank: p < 0.001) as compared with those in the lower quintiles (n = 10,201) during mean follow-up of 3 years. Increased risk of highest SDI for all-cause mortality and CHF remained significant after adjustment in multivariable analysis for factors associated with highest SDI. Conclusions: Patients within the highest SDI quintile had a greater proportion of comorbidities as well as higher risk for adverse outcomes as compared with patients with a lower SDI following PCI.
MeSH term(s)	Humans ; Percutaneous Coronary Intervention/adverse effects ; Treatment Outcome ; Risk Factors ; Retrospective Studies ; Heart Failure/therapy ; Heart Failure/etiology ; Social Deprivation ; Coronary Artery Disease/diagnostic imaging ; Coronary Artery Disease/therapy ; Coronary Artery Disease/etiology
Language	English
Publishing date	2023-03-30
Publishing country	United States
Document type	Observational Study ; Multicenter Study ; Journal Article
ZDB-ID	1459995-8
ISSN	1522-726X ; 1522-1946
ISSN (online)	1522-726X
ISSN	1522-1946
DOI	10.1002/ccd.30642
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Article: Pharmacogenomics of Novel Direct Oral Anticoagulants: Newly Identified Genes and Genetic Variants.

Kanuri, Sri H / Kreutz, Rolf P

Journal of personalized medicine

2019 Volume 9, Issue 1

Abstract: ... drug interactions of dabigatran are mainly mediated by p-glycoprotein. Strong inhibitors and inducers of CYP3A4 and ... p-glycoprotein should be avoided in patients treated with rivaroxaban, apixaban, and edoxaban ...

Abstract	Direct oral anticoagulants (DOAC) have shown an upward prescribing trend in recent years due to favorable pharmacokinetics and pharmacodynamics without requirement for routine coagulation monitoring. However, recent studies have documented inter-individual variability in plasma drug levels of DOACs. Pharmacogenomics of DOACs is a relatively new area of research. There is a need to understand the role of pharmacogenomics in the interpatient variability of the four most commonly prescribed DOACs, namely dabigatran, rivaroxaban, apixaban, and edoxaban. We performed an extensive search of recently published research articles including clinical trials and in-vitro studies in PubMed, particularly those focusing on genetic loci, single nucleotide polymorphisms (SNPs), and DNA polymorphisms, and their effect on inter-individual variation of DOACs. Additionally, we also focused on commonly associated drug-drug interactions of DOACs. CES1 and ABCB1 SNPs are the most common documented genetic variants that contribute to alteration in peak and trough levels of dabigatran with demonstrated clinical impact. ABCB1 SNPs are implicated in alteration of plasma drug levels of rivaroxaban and apixaban. Studies conducted with factor Xa, ABCB1, SLCOB1, CYP2C9, and VKORC1 genetic variants did not reveal any significant association with plasma drug levels of edoxaban. Pharmacokinetic drug-drug interactions of dabigatran are mainly mediated by p-glycoprotein. Strong inhibitors and inducers of CYP3A4 and p-glycoprotein should be avoided in patients treated with rivaroxaban, apixaban, and edoxaban. We conclude that some of the inter-individual variability of DOACs can be attributed to alteration of genetic variants of gene loci and drug-drug interactions. Future research should be focused on exploring new genetic variants, their effect, and molecular mechanisms that contribute to alteration of plasma levels of DOACs.
Language	English
Publishing date	2019-01-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm9010007
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Article: Analysis of the Combined Effect of rs699 and rs5051 on Angiotensinogen Expression and Hypertension.

Powell, Nicholas R / Shugg, Tyler / Leighty, Jacob / Martin, Matthew / Kreutz, Rolf P / Eadon, Michael T / Lai, Dongbing / Lu, Tao / Skaar, Todd C

bioRxiv : the preprint server for biology

2023

Abstract: Hypertension (HTN) involves genetic variability in the renin-angiotensin system and characterizing this variability will help advance precision antihypertensive treatments. We previously reported that angiotensinogen ( ...

Abstract	Hypertension (HTN) involves genetic variability in the renin-angiotensin system and characterizing this variability will help advance precision antihypertensive treatments. We previously reported that angiotensinogen (
Language	English
Publishing date	2023-04-08
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.07.536073
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Article ; Online: MicroRNA sequencing in patients with coronary artery disease - considerations for use as biomarker for thrombotic risk.

Onuoha, Chimnonso P / Ipe, Joseph / Simpson, Edward / Liu, Yunlong / Skaar, Todd C / Kreutz, Rolf P

Clinical and translational science

2022 Volume 15, Issue 8, Page(s) 1946–1958

Abstract: ... between subjects with and without recurrent MI events (p < 0.05), with 69 remaining significant after ...

Abstract	MicroRNAs (miRNAs) are small RNAs integral in the regulation of gene expression. Analysis of circulating miRNA levels may identify patients with coronary artery disease (CAD) at risk for recurrent myocardial infarction (MI) after percutaneous coronary interventions (PCIs). Subjects with CAD were selected from the GENCATH cardiac catheterization biobank. Subjects with recurrent MI after PCI were compared with those without recurrent MI during follow-up in the initial (n = 48) and replication cohort (n = 67). Next generation MiRNA sequencing was performed on plasma samples and whole blood samples fixed with PAXGENE tubes upon collection. Overall, 164 miRNAs derived from whole blood were differentially expressed in the replication cohort between subjects with and without recurrent MI events (p < 0.05), with 69 remaining significant after false-discovery rate (FDR) correction. None of the miRNAs in plasma was significantly different by FDR among subjects with and without MI. Overall, correlation between direction of effects between plasma and whole blood assays was variable, and only two miRNAs were concordant and significant in both. Associations of miRNA with vascular disease, MI, and thrombosis were further explored. MiRNA profiling has potential as the future biomarker for disease prognosis and treatment response marker in secondary treatment of patients with CAD after PCI. Whole blood may be the preferred sample source as compared to plasma.
MeSH term(s)	Biomarkers ; Coronary Artery Disease/diagnosis ; Coronary Artery Disease/genetics ; Humans ; MicroRNAs/genetics ; Percutaneous Coronary Intervention/adverse effects ; Thrombosis/etiology ; Thrombosis/genetics
Chemical Substances	Biomarkers ; MicroRNAs
Language	English
Publishing date	2022-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2433157-0
ISSN	1752-8062 ; 1752-8054
ISSN (online)	1752-8062
ISSN	1752-8054
DOI	10.1111/cts.13307
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Article: Impact of Routine Platelet Reactivity Testing with VerifyNow Assay on Antiplatelet Choice After Percutaneous Coronary Intervention.

Mshelbwala, Fakilahyel S / Hugenberg, Daniel W / Kreutz, Rolf P

Clinical pharmacology : advances and applications

2020 Volume 12, Page(s) 35–41

Abstract: ... to those who did not have VN assay done (57% vs. 50%, p=0.039). There was no significant difference in 1-year net ... testing) as compared to standard of care group (adjusted HR:0.92, 95% CI: 0.54-1.5, p=0.74).: Conclusion ...

Abstract	Background: High on-treatment ADP platelet reactivity (HPR) measured by VerifyNow P2Y12 assay (VN) is an established risk factor for ischemic events after percutaneous coronary intervention (PCI). We hypothesized that routine use of VN at time of PCI in clinical practice may affect choice of P2Y12 antiplatelet therapy at discharge. Methods: In a single center retrospective analysis, we examined the influence of VN testing on choice of P2Y12 inhibitor post PCI in routine clinical practice. Assessment of HPR was used routinely in clinical care during the time period of analysis at discretion of clinical providers. Subjects with PRU>208 after the loading dose of clopidogrel or during clopidogrel steady state were switched to alternate P2Y12 inhibitors. Results: We identified 1001 patients with PCI during the time period specified. A total of 252 subjects underwent VN testing. Among those, 43% were found to have HPR on clopidogrel and were switched to alternate therapies (prasugrel [n=60], ticagrelor [n=48]). Patients who had VN platelet function testing were more likely to be discharged on clopidogrel as compared to those who did not have VN assay done (57% vs. 50%, p=0.039). There was no significant difference in 1-year net-MACE (CVD, MI, stent thrombosis, BARC 2 or higher bleeding) using tailored antiplatelet therapy (VN testing) as compared to standard of care group (adjusted HR:0.92, 95% CI: 0.54-1.5, p=0.74). Conclusion: Routine use of VN assay in personalized antiplatelet treatment decision-making after PCI is associated with lower likelihood of using novel P2Y12 inhibitors.
Language	English
Publishing date	2020-04-16
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2520726-X
ISSN	1179-1438
ISSN	1179-1438
DOI	10.2147/CPAA.S242675
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Article ; Online: Intensified P2Y12 inhibition for high-on treatment platelet reactivity.

Mshelbwala, Fakilahyel S / Hugenberg, Daniel W / Kreutz, Rolf P

Journal of thrombosis and thrombolysis

2020 Volume 50, Issue 3, Page(s) 619–627

Abstract: ... CI 1.1-11.1); p = 0.036)]. Propensity score matched analysis demonstrated higher event rates ... in patients with HPR on alternate P2Y12 inhibitor as compared to patients with LPR (log-rank: p = 0.044 ...

Abstract	High on treatment platelet reactivity (HPR) during treatment with clopidogrel has been consistently found to be strong risk factor for recurrent ischemic events after percutaneous coronary intervention (PCI). Insufficient P2Y12 receptor inhibition contributes to HPR measured by the VerifyNow (VN) assay. Prasugrel and ticagrelor are more potent P2Y12 inhibitors than clopidogrel and commonly substituted for clopidogrel when HPR is documented, however benefit of VN guided intensified antiplatelet therapy is uncertain. We identified patients who had undergone platelet reactivity testing after PCI with VN after pretreatment with clopidogrel (n = 252) in a single center observational analysis. Patients who had HPR defined as PRU > 208 were switched to alternate P2Y12 inhibitors. Primary clinical endpoint was 1-year post PCI combined cardiovascular death, myocardial infarction (MI), and stent thrombosis. One hundred and eight (43%) subjects had HPR and were switched to prasugrel (n = 60) and ticagrelor (n = 48). Risk of recurrent 1-year primary endpoint remained higher for HPR patients switched to either ticagrelor or prasugrel as compared to subjects who had low on treatment platelet reactivity (n = 144) (LPR) on clopidogrel [Hazard Ratio: 3.5 (95% CI 1.1-11.1); p = 0.036)]. Propensity score matched analysis demonstrated higher event rates in patients with HPR on alternate P2Y12 inhibitor as compared to patients with LPR (log-rank: p = 0.044). The increased risk of recurrent events associated with HPR measured by VN is not completely attenuated by switching to more potent P2Y12 inhibitors. Non-P2Y12 mediated pathways likely contribute to increased incidence of thrombotic events after PCI in subjects with HPR.
MeSH term(s)	Aged ; Blood Platelets/drug effects ; Blood Platelets/metabolism ; Clopidogrel/therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention/adverse effects ; Platelet Activation/drug effects ; Platelet Aggregation Inhibitors/therapeutic use ; Prasugrel Hydrochloride/therapeutic use ; Purinergic P2Y Receptor Antagonists/therapeutic use ; Receptors, Purinergic P2Y12/metabolism ; Retrospective Studies ; Thrombosis/etiology ; Thrombosis/prevention & control ; Ticagrelor/therapeutic use
Chemical Substances	P2RY12 protein, human ; Platelet Aggregation Inhibitors ; Purinergic P2Y Receptor Antagonists ; Receptors, Purinergic P2Y12 ; Clopidogrel (A74586SNO7) ; Prasugrel Hydrochloride (G89JQ59I13) ; Ticagrelor (GLH0314RVC)
Language	English
Publishing date	2020-03-10
Publishing country	Netherlands
Document type	Journal Article ; Observational Study
ZDB-ID	1230645-9
ISSN	1573-742X ; 0929-5305
ISSN (online)	1573-742X
ISSN	0929-5305
DOI	10.1007/s11239-020-02075-x
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