Dataset Information

Thiazide Exposure and Cardiovascular Risk in Type 2 Diabetes Mellitus: A Point of Clarification.

ABSTRACT: A recently published analysis in Hypertension suggests that thiazide use, versus nonuse, is associated with excess risk of adverse cardiovascular outcomes in patients with diabetes mellitus enrolled in the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes). Here, we replicate these findings using the same publicly available datasets and following their reported methods. We further show that possible misclassification of thiazide exposure exists in the original analysis. We perform alternative analyses that correct for this misclassification to highlight the impact that misclassification can have on observed associations between an exposure (eg, thiazides) and outcomes (eg, stroke and major adverse cardiovascular events).

SUBMITTER: Smith SM

PROVIDER: S-EPMC7035168 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Thiazide Exposure and Cardiovascular Risk in Type 2 Diabetes Mellitus: A Point of Clarification.

Smith Steven M SM Winterstein Almut G AG Pepine Carl J CJ Cooper-DeHoff Rhonda M RM

Hypertension (Dallas, Tex. : 1979) 20200203 3

A recently published analysis in <i>Hypertension</i> suggests that thiazide use, versus nonuse, is associated with excess risk of adverse cardiovascular outcomes in patients with diabetes mellitus enrolled in the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes). Here, we replicate these findings using the same publicly available datasets and following their reported methods. We further show that possible misclassification of thiazide exposure exists in the original analysis. We p ...[more]

PMID: 32008437

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Project description:BackgroundType 2 diabetes mellitus (T2D), rapidly increasing to epidemic proportions, globally escalates cardiovascular disease risk. Although intensive interventions and comprehensive management of environmental risks factors for T2D are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic T2D risk. In this study we investigated possible associations of ACE2 polymorphisms and cardiovascular risks in Uygur patients with T2D.Methods275 Uygur T2D patients and 272 non-diabetic Uygur individuals were enrolled as study participants. 14 ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry.ResultsACE2 SNP rs1978124, rs2048683, rs2074192, rs233575, rs4240157, rs4646156, rs4646188 and rs879922 were associated with T2D (all P < 0.05). The 8 diabetic risk related ACE2 SNPs were further associated with diabetic related cardiovascular complications or events but exhibited heterogeneity as fellows: firstly, almost all diabetic risk related ACE2 SNPs (all P < 0.05) were associated with increased SBP except rs1978124 and rs2074192, while rs2074192, rs4646188 and rs879922 were associated elevated DBP (all P < 0.05). Secondly, SNP rs4646188 was not correlated with any type of dyslipidemia (TRIG, HDL-C, LDL-C or CHOL), and the other 7 diabetic risk related loci were at least correlated with one type of dyslipidemia (all P < 0.05). In particular, rs879922 were simultaneously correlated with four type of dyslipidemia (all P < 0.05). Thirdly, ACE2 SNP rs2074192 and rs879922 were associated with carotid arteriosclerosis stenosis (CAS) ≥ 50% (both P < 0.05). Fourthly, ACE2 SNP rs2074192, rs4240157, rs4646188 and 879922 were associated with increased MAU (all P < 0.05). In addition, ACE2 SNP rs2048683, rs4240157, rs4646156, rs4646188 and rs879922 were linked to heavier LVMI (all P < 0.05), but only rs4240157, rs4646156 and rs4646188 were associated with lower LVEF (all P < 0.05).ConclusionACE2 SNP rs879922 may be a common genetic loci and optimal genetic susceptibility marker for T2D and T2D related cardiovascular risks in Uygurs.

Dataset Information

Thiazide Exposure and Cardiovascular Risk in Type 2 Diabetes Mellitus: A Point of Clarification.

Publications

Thiazide Exposure and Cardiovascular Risk in Type 2 Diabetes Mellitus: A Point of Clarification.

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