This study was conducted to investigate the relationship of impaired lung functions with resting electrocardiographic ST-T abnormalities in a cross-sectional analysis of asymptomatic adults without past history of heart disease. We found that LFVC and probably low FEV1, but not low FEV1/FVC, were significantly associated with ST-T abnormalities, which was attenuated by further adjustment for cardiometabolic risk factors, diabetes (presumably mostly type 2 diabetes in this study), or MetS, but remained significant. Notably, cardiometabolic risk factors included circulating CRP and waist circumference, surrogate markers of systemic inflammation, and amount of abdominal fat, respectively. Collectively, the current findings suggest that LFVC, which often reflects restrictive pulmonary function pattern, may be independently associated with ST-T abnormalities irrespective of clinical confounders, diabetes, and MetS, whereas obstructive pulmonary function defects are not.
So far, no clinical study has examined the relationship of LFVC with electrocardiographic abnormalities with the exception of a study by Sideris and Katsadoros [23
]. This study reported a negative correlation between vital capacity and number of abnormalities, such as a rightward shift of the P-wave and clockwise rotation of QRS, but it did not address ST or T-wave abnormalities. Thus, to our knowledge, this study is the first to demonstrate the association between LFVC and ST-T abnormalities, which is conceivably prognostic for cardiovascular events in asymptomatic people [14
According to previous studies, LFVC and restrictive pulmonary defects have been associated with coronary artery calcification [5
] and arterial stiffness [3
]. Because artery calcification and arterial stiffness generally reflect atherosclerosis and ischemic cardiovascular diseases, the current results are consistent with these previous studies. Generally, ST-T abnormalities are observed in various conditions, such as ischemia, hypokalemia, cardiomyopathy, and pulmonary embolism [15
]. Ohira et al. [13
] mentioned that minor ST-T abnormalities may reflect an end-organ effect of long-term hypertension because hypertensive men with minor ST-T abnormalities tended to have longer durations of hypertension in their study. Indeed, arterial stiffness assessed with pulse-wave velocity is substantially affected by hypertension [24
]. Furthermore, a recent study showed that decline in FVC predicted incident hypertension in young apparently healthy individuals [22
]. Actually, in our study, LFVC was robustly associated with hypertension, even after full adjustments for critical confounders. Nevertheless, the significant association between LFVC and ST-T abnormalities persisted after further adjustments for confounders plus hypertension or medication for hypertension. Therefore, although hypertension likely contributes in part to the observed associations through the close interrelationship of lung with cardiovascular system, other unknown factors may principally interfere with the associations between LFVC and ST-T abnormalities.
Considering that LFVC was associated with ST-T abnormalities independently of cardiometabolic factors, circulating CRP, diabetes, and MetS, which are proatherosclerotic and proinflammatory [9
], several factors not examined in this study, such as insulin resistance, oxidative stress, or subclinical hypoxia, might interfere with the relationship between LFVC and ST-T abnormalities. In accordance with this, previous studies have hypothesized that insulin resistance is a fundamental element for the pathophysiology of LFVC and restrictive lung function [2
Meanwhile, many studies in the past decade have shown that a predisposition for cardiovascular disease and impaired pulmonary functions (low vital capacity and low FEV1
) are associated with low birth weight [25
], possibly via physiological alterations such as increased adrenocortical and sympathoadrenal responses to an adverse fetal environment [27
]. LFVC and ST-T abnormalities might then relate to such potential factors as epiphenomena.
Alternatively, physicochemical factors might interfere with the associations. Of note, the American Heart Association recently updated its scientific statement to describe that exposure to particulate-matter air pollution contributes to cardiovascular morbidity and mortality [28
]. It highlighted several possible biological mechanisms secondary to pulmonary oxidative stress, inflammation, and an impaired lung autonomic nervous system that might result in vascular dysfunction and ST-segment depression irrespective of metabolic abnormalities.
Several limitations should be mentioned. First, because of the nature of cross-sectional studies, causality remains unknown and must be elucidated in large prospective studies. Second, it was not possible to distinguish between major and minor ST-T abnormalities in this study because the electrocardiogram findings on individual checkup sheets in combinations of major and minor ST-T abnormalities were recorded together indistinguishably. However, most ST-T abnormalities were likely to be minor ST-T abnormalities because the prevalence of minor ST-T abnormalities is approximately 2-fold greater than that of major ST-T abnormalities in the Japanese population [13
Third, all subjects in this study were instructed by staff members trained in spirometry, and the subjects performed a few rehearsals. Nevertheless, it was not clear whether all subjects had acceptable results in the actual test, especially the elderly, regardless of cognitive status, physical performance, or education level. This is likely to result in potential bias of the outcomes.
Finally, most subjects were healthy with good profiles in terms of various parameters, although a small portion of them had several critical conditions such as diabetes or history of stroke. Therefore, the current findings may not be applicable to other populations that have more cardiometabolic risk factors and ST-T abnormalities, where the observed associations, if any, might be dependent on hypertension, diabetes, or metabolic syndrome.