Critical Appraisal of Studies of Aetiology

This article provides a critical appraisal of studies of aetiology, specifically focusing on the impact of oxidative stress-related gene polymorphisms on the risk of coronary heart disease in patients with type 2 diabetes. The study discusses the life course model and its relevance to understanding the socio-economic aspects and history of disease. The findings suggest that oxidative stress and genetic vulnerabilities play a significant role in the development of coronary heart disease in patients with diabetes. However, the study also highlights limitations in the research methodology and the need for further investigation.

Running head: CRITICAL APPRAISAL OF STUDIES OF AETIOLOGY
CRITICAL APPRAISAL OF STUDIES OF AETIOLOGY
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Article selected for this paper
Katakami, N., Kaneto, H., Matsuoka, T. A., Takahara, M., Osonoi, T., Saitou, M., ... &
Shimomura, I. (2014). Accumulation of oxidative stress-related gene polymorphisms and the risk
of coronary heart disease events in patients with type 2 diabetes–an 8-year prospective
study. Atherosclerosis, 235(2), 408-414.
Question 1
Life course model mentioned in the paper
As per Astell-Burt, Mitchell and Hartig (2014), the life course model of epidemiological
study of disease discusses about the physical and social exposure of people to different stressors
due to which, people and their health in later stage of life is affected. This life course model
helps the healthcare professionals to understand the socio- economic aspects, the history of
disease so that the occurrence of chronic disease and health outcomes could be achieved (Kuh et
al., 2014).
In this paper by Katakami et al. (2014), the discussed life curse model was related to
oxidative stress due to which patients with diabetes develops risk of coronary heart disease.
The period of the life course which was associated to this higher risk factor is more than 60 years
of age, when the environmental and life event stressors affects the cardiac system and modifies
the genotype to develop coronary heart disease among patients.
The paper provided a detailed hypothesis through which the life course incidence could
affect the life of the patient. Oxidative stress and resultant vulnerabilities are associated to the
genetic background of the person. As per Harris et al. (2015), glutathione is the primary

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antioxidant available in most of the cells and helps to regulate the redox state so that those cells
could be protected from the oxidative injury. However, due to the environmental stress, the
catalytic subunit of the Glutamate cysteine ligase, increases the rate of GSH limiting enzyme
synthesis. Due to this, the gene expression for the GSH prevented and the oxidative stress of the
person increases. However, in hypothesis for the increased risk factor for the coronary heart
disease and associated side effects of oxidative stress, determinants of these gene polymorphisms
and the predicted occurrence of coronary heart disease in patients with type 2 diabetes mellitus
was not provided strongly and hence, this was the research topic of this selected article.
While summarizing the findings of this paper, it was seen that after 7.5 years of exposure
to life events and stresses, 85 events of coronary heart disease was observed in the patients as
well as 198 cardio vascular diseases was observed (Katakami et al., 2014). All these participants
of the 3 participatory hospitals were analyzed and it was found that stress and depression was the
primary reasons due to which patients developed hypertension, and dyslipidemia. Further, due to
the 5 genotype associated polymorphism in the genotype of the patients, their risk of
development of coronary heart disease increased (Katakami et al., 2014). However, while
statistical analysis; no such significant data connecting both these events were identified.
Answer 2
As per this study, three type of study were conducted so that the association between the
environmental stressors, life events, gene-polymorphism and the occurrence of coronary heart
disease could be assessed (Katakami et al., 2014). These studies were finding connection
between individual oxidative stresses and gene polymorphism that leads to CHD, oxidative stress
associated factors that lead to gene polymorphism and the CHD and CVD associated results. For

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the first study, the associated was dependent on the 85 HD events, 13 peripheral heart diseases,
97 cerebro-vascular diseases, and 3 heart failure diseases were assessed so that the evidence
based on the disease association could be assessed (Katakami et al., 2014). Further, on the
second and third study, population of 11 subgroups of 3 hospitals were selected so that the
coronary risk factor such as BMI, hypertension, dyslipidemia, smoking status could be assessed
and the analysis of linkage between CHD and life event stressed could be assessed.
The study design selected for the paper was prospective study and depending on it, the
cohort study for the research process was selected. As per Katakami et al. (2014), the study
selected for this research process was successful in determining effectiveness of the chosen
strategy, preventive strategies, and public health interventions and so on. Hence, choosing this
study approach for this research process was effective in determining the association between the
life events, stress and environmental factors in exerting negative effects on the patient and
generation of coronary heart diseases. However, despite of proper result and analysis of the
research, statistical data did not showed any effective relationship between coronary heart
disease and hypertension (Katakami et al., 2014).
Answer 3
Starting from the disease association mishap, inability of the study approach to provide
accurate association between the diseases in concern, the study included several limitations
(Katakami et al., 2014). The first limitation was associated to the study population as within all
the participants included in the study, the number of minor allele’s homozygote was inadequate
due to which, it was difficult to find the association between the polymorphism and occurrence
of CHD (Katakami et al., 2014). Second limitation was associated to the measurement of

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oxidative stress which was inaccurate and hence, the influence of this specific aspect on the
occurrence was not assessed properly (Katakami et al., 2014). Third limitation was associated to
the study population and their risk factor related to CHD and type 2 diabetes mellitus. As per the
researchers the risk factor for CHD among Japanese people are very low and it is 5.7 people
within 1000 included. Further, it was also seen that among western community the rate of both
these disorders were higher. Hence, choosing western population would have provided the
researchers with abilities so that the link between the oxidation stress, and emerging CHD could
be assessed. These were the key limitations of the methodology of the study conducted by
Katakami et al. (2014). Besides these, the study did not included the very important perspective
of smoking habit, gender and the connection of these with increased stress on the human and
hence, only polymorphism with oxidative stress were mentioned. However, as per Angiolillo et
al. (2014), these factors are also associated to the emergence of CHD in patients with type 2
diabetes mellitus. Hence, these aspects contributed to the non-casual mechanism.

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References
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Shimomura, I. (2014). Accumulation of oxidative stress-related gene polymorphisms and
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