Total impact of oxidative stress genes on cardiovascular events-a 7-year follow-up study

Abstract

Cardiovascular (CV) events are the number one cause of lifetime disability and deaths worldwide. It is well known that traditional risk factors do not fully correlate with clinical outcomes; therefore, searching for other markers that would explain CV events' occurrence seems essential. Of importance, one of the main factors at the origin of CV events is oxidative stress, causing inflammation and atherosclerotic plaque instability. Therefore, the present study was conducted to evaluate eight carefully selected genetic polymorphisms related to oxidative stress as risk modifiers for CV events. A cohort of 1020 patients with coronary atherosclerosis was analysed in a 7-year follow-up observational study. The following end points were assessed: CV death, myocardial infarction (MI) and a combined end point of CV death/MI/stroke. Our results show that single polymorphisms are not significant cardiovascular disease risk factors, but genetic risk score (GRS), defined as the accumulation of our eight studied polymorphisms, was significantly associated with the three. Specifically, low GRS was associated with a higher risk of CV death, MI and CV death/MI/stroke. In conclusion, when regarding CV events, GRS investigated here can become clinically meaningful and undoubtedly adds to the knowledge in stratifying the risk of CV events.

Keywords: CV events; Cardiovascular disease; GRS; Gene polymorphism; Oxidative stress; SNP.

Fig. 1

The inclusion and exclusion criteria of the patients recruited into the study

Fig. 2

Distribution of risk alleles and GRS models

Fig. 3

A The cumulative probability of CV death in patients with < 4, 4–5, 6–7 and ≥ 8 risk alleles. There was a trend that reveals differences in CV death rate between the GRS groups (p = 0.092). B The cumulative probability of CV death in patients with < 4 (n = 179) and ≥ 4 risk alleles (n = 843). The risk of CV death was significantly lower in the group with ≥ 4 atherosclerosis risk alleles (p = 0.024). 7-year Kaplan-Meyer curves of probability of CV death (95% Hall-Wellner bands (B)). A log-rank test was used to evaluate the difference in MI incidence between patients with various GRS

Fig. 4

A The cumulative probability of MI in patients with < 4, 4–5, 6–7 and ≥ 8 risk alleles. There was a trend that reveals differences in MI rate between the GRS groups (p = 0.069). B The cumulative probability of MI in patients with < 4 (n = 179) and ≥ 4 risk alleles (n =843). The risk of MI was significantly lower in the group with ≥ 4 atherosclerosis risk alleles (p = 0.0097). 7-year Kaplan-Meyer curves of probability of MI (95% Hall-Wellner bands (B)). A log-rank test was used to evaluate the difference in MI incidence between patients with various GRS

Fig. 5

A The [DCJR1] cumulative probability of CVdeath/MI/stroke in patients with < 4, 4–5, 6–7 and ≥ 8 risk alleles. There was a statistically significant difference in CVdeath/MI/stroke rate between the GRS groups (p = 0.031). B The cumulative probability of CVdeath/MI/stroke in patients with < 4 (n = 179) and ≥ 4 risk alleles (n = 843). The risk of CVdeath/MI/stroke was significantly lower in the group with ≥ 4 atherosclerosis risk alleles (p = 0.0035). 7-year Kaplan-Meyer curves of probability of CVdeath/MI/stroke (95% Hall-Wellner bands (B)). A log-rank test was used to evaluate the difference in CVdeath/MI/stroke incidence between patients with various GRS