Key result
The variant ALDH2*2 genotype exacerbated nitrate tolerance after 48h of continuous glyceryl trinitrate in coronary spastic angina patients compared to wild ALDH2*1/*1 (NMD 6.0% vs 12.2%, P=0.0002).
Why the study?
It was unknown whether NMD and FMD responses to continuous glyceryl trinitrate differ between wild ALDH2*1/*1 and deficient variant ALDH2*2 patients with CAD.
Does the variant ALDH2*2 genotype exacerbate nitrate tolerance and endothelial dysfunction compared to the wild ALDH2*1/*1 genotype in patients with coronary spastic angina receiving continuous glyceryl trinitrate?
Observational (n=55)
Single-blind
No
Does the variant ALDH2*2 genotype exacerbate nitrate tolerance and endothelial dysfunction compared to the wild ALDH2*1/*1 genotype in patients with coronary spastic angina receiving continuous glyceryl trinitrate?
Absolute Event Rate: 6% vs 12.2%
p-value: p=0.0002
Continuous administration of glyceryl trinitrate produces nitrate tolerance and endothelial dysfunction in patients with coronary spastic angina, which is significantly exacerbated in those with the variant ALDH2*2 genotype.
ALDH2*2 may worsen nitrate tolerance during continuous GTN in CSA; leaves open whether genotyping should inform therapy.
BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2) plays a central role in the biotransformation of glyceryl trinitrate (GTN) or nitroglycerin, which is widely used for the treatment of coronary artery disease (CAD). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. This study examined whether there are differences in nitroglycerine-mediated dilation (NMD) and flow-mediated dilation (FMD) response between wildALDH2*1/*1and variantALDH2*2patients with CAD. METHODS AND RESULTS: The study subjects comprised 55 coronary spastic angina (CSA) patients, confirmed by coronary angiography and intracoronary injection of acetylcholine (42 men and 13 women, mean age 68.0±9.0 years). They underwent NMD and FMD tests in the morning before and after continuous transdermal GTN administration for 48 h. NMD was lower at baseline inALDH2*2than in theALDH2*1/*1group (P=0.0499) and decreased significantly in both groups (P<0.0001 and P<0.0001, respectively) after GTN, with significantly lower levels in theALDH2*2group (P=0.0002). FMD decreased significantly in bothALDH2*1/*1andALDH2*2groups (P<0.0001and P=0.0002, respectively) after continuous GTN administration, with no significant differences between the 2 groups both before and after GTN. CONCLUSIONS: Continuous administration of GTN produced endothelial dysfunction as well as nitrate tolerance in bothALDH2*1/1andALDH2*2patients with CSA.ALDH2*2attenuated GTN response and exacerbated GTN tolerance, but not endothelial dysfunction, as compared toALDH2*1/*1in patients with CSA.
No takes yet. Share an insight, caveat, or question.
Mizuno et al. (2020) conducted an observational in Coronary spastic angina (n=55). Variant ALDH2*2 genotype vs. Wild ALDH2*1/*1 genotype was evaluated on Nitroglycerine-mediated dilation (NMD) after continuous GTN administration (p=0.0002). The variant ALDH2*2 genotype exacerbated nitrate tolerance after 48h of continuous glyceryl trinitrate in coronary spastic angina patients compared to wild ALDH2*1/*1 (NMD 6.0% vs 12.2%, P=0.0002).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: