The decreasing trend (from 66.9% to 54.4%) of seroprevalence of H. pylori over 13 years was explained by birth cohort analysis, and a relationship between H. pylori infection and high cholesterol level was found in this large cohort.
A drop in the seroprevalence of H. pylori infection has been observed in previous studies [2, 3, 13]. This trend was most often explained by a combination of various factors including rapid economic growth, improved sanitation, and widespread use of antibiotics and proton pump inhibitors [2, 3]. Similarly, the overall seroprevalence of H. pylori significantly decreased in the last survey of the Korean population in 2005 [9] compared with that in 1998 [10], but the declining trend was different depending on the age groups and areas. Although the drop in H. pylori infection was bigger in younger age groups of subjects 40 years old or less for seven years from 1998 to 2005, the difference of seroprevalence in older groups during same periods was smaller, as shown in the upper two lines of figure 2C. In addition, regarding areas, only subjects who lived in Seoul (capital) and Gyeonggi province which surrounds the capital, showed a clear declining trend during the same periods, but not in all districts in previous study [9]. Furthermore, subjects who lived in Chungcheong province showed a slight increase between 1998 and 2005.
However, when we extended the time period to 2011 in this study, this decreasing trend was more prominent for all ages over 13 years. Similarly, a Japanese study of seropositivity trends of H. pylori over a period of 10 years from 1992 to 2002–2006 also found declining trends of seropositivity for all age groups [13]. Regarding province, there was no increasing pattern in any province, and a statistically significant decreasing trend was observed in all provinces except two provinces, Kyungsang and Kangwon areas.
We also analyzed birth cohort effects. In the cross sectional study, the prevalence of H. pylori infection increased till 40 – 49 years of age, after which it remained steady. When we graphically drew the prevalence in H. pylori infection by birth cohort to differentiate the increase of infection during aging, the seroprevalence was lower in younger birth cohort (i.e. people who were born later) than the older birth cohort (people who were born earlier) at the same age, showing a clear cohort effect in subjects up to 40–45 years of age. This phenomenon could be explained by continuous influx of younger birth cohorts [7]. A similar birth cohort effect for H. pylori infection was observed in Western studies [2, 3, 7, 8]. In addition, H. pylori infection in adults is mostly acquired by the age of 15 years [7, 8]. One study which followed children (1–3 years old) for 21 years indicated that the annual seroconversion rate had a highest risk at the age of 4–5 years, and newly acquired H. pylori infections mostly occurred by the age of 10 years [14]. However, there is a doubt whether only a birth cohort effect could explain this pattern. That is, one study in Canada mentioned that an increasing pattern of H. pylori infection with advancing age may be due to the continuous risk of infection in adults rather than cohort effects [6]. The decrease of H. pylori seroprevalence with advancing age within the same birth cohort in our study strongly suggests that aging is not likely to raise risk of H. pylori infection. There was a decreasing effect with advancing age within the same birth cohorts. This might have occurred as a result of cases taking antibiotics or proton pump inhibitors even without formal eradication therapy of H. pylori[15].
There have been several studies regarding risk factors of H. pylori infection [9, 14, 16–18], but their results are still unclear, except socioeconomic status as the risk factors. Our results also showed that lower social economic status is associated with the risk of H. pylori infection in a cross sectional analysis. Furthermore, subjects with lower social economic status had a lower likelihood of taking H. pylori eradication therapy in the present study. Interestingly, our study showed a relationship between cholesterol level and seropositivity of H. pylori. Subjects who had a TC level of ≥240 mg/dl were 1.3 times more likely to be seropositive for H. pylori. In frequency analysis, higher levels of TG and glucose as well as TC were also associated with H. pylori infection, but after adjusting for demographic variables, clinical information, and socioeconomic status(i.e. age, BMI, income and etc.), only TC among metabolic parameters was related to H. pylori infection. So far, the results regarding the relationship between lipid parameters such as TC, TG and low-density lipoprotein cholesterol (LDL-C) levels and H. pylori seropositivity have not been consistent. Some studies [19–21] reported no relationship, but several studies reported higher atherogenic lipid parameter levels in H. pylori seropositive subjects in comparison with seronegative ones [22–24] as seen in the present study. Our study results could be convincing for demonstrating the effect of H. pylori infection on atherosclerotic disease because the positive relationship between TC and H. pylori seropositivity was persistent even after adjustment for BMI and age in a large cohort. The mechanism of how H. pylori infection modifies the serum lipid profiles is still not clear, but a plausible explanation is that systemic inflammatory response to the bacterium induces changes in lipid and lipoprotein metabolism [25]. That is, chronic H. pylori infection has been postulated to shift the lipid profile toward an atherogenic direction via the action of proinflammatory cytokines, such as interleukins 1 and 6, interferon-alpha, and tumor necrosis factor-alpha. These cytokines are capable of affecting lipid metabolism in various ways, including activation of adipose tissue lipoprotein lipase, stimulation of hepatic fatty acid synthesis, influencing lipolysis and the increasing hepatic HMG-CoA reductase activity [26, 27]. Thus, H. pylori infection could play a role in the atherosclerotic process and may be a reliable indicator for the assessment of cardiovascular disease risk.
There are several limitations which should be acknowledged in this study. First, the relationship between H. pylori infection and its risk factors in the cross sectional study could not be proven conclusively. However, this is an unavoidable limitation in the cross sectional study. Second, we compared the time trends of seroprevalence of H. pylori using two previous studies [9, 10]. However, the responsible author (N.K.) did play main role in these previous studies, and the population in 2011 study was restricted to have comparability of H. pylori seroprevalence. In other words, the subjects in 2011 study were restricted to asymptomatic people without a history of H. pylori eradication and GI operation. Moreover, this study was carried out nationwide, so our findings represent a national trend, not a local phenomenon. Nonetheless, the study subjects in 1998 involved a relatively lower population from Seoul and Gyeonggi, (capital city and its near city) compared with the population in 2005 and 2011. Generally people in capital cities have higher socioeconomic conditions than those living in other areas. It may account for much higher seroprevalence in 1998 compared with 2005/2011. However, the change of seroprevalence by the strata (e.g. age, sex, region, etc.) over time periods may indicate that our overall result is not much influenced by a different proportion of subjects from provinces. Third, for the generation of synthetic cohort, cross-sectional data should have the same interval. However, our data did not have the same interval as the previous data. This is the reason why we considered the data from 1998 as equivalent to those from 1999. This intentional modification could have caused bias, but we think that the bias may be negligible because H.pylori seroprevalence was not changed much by one-year.