The present analysis of a population-based study demonstrates that both high blood pressure and the use of BBL are associated with reduced lung function, whereas other antihypertensive medications have no effect on lung function.
Our findings are in line with previous observations that blood pressure and lung function are inversely associated [5, 6, 9]. But most of these studies did not differentiate between the effect of high blood pressure and the effect of antihypertensive medication on lung function. Instead they defined hypertension as elevated blood pressure or use of antihypertensive medication. One study, however, found no difference in FEV1 and FVC between hypertensive subjects that used or did not use beta blocking antihypertensives , but they did not specifically address the effect of antihypertensive medication independent of high blood pressure on lung function.
Thus, our study might substantially add to the question, whether antihypertensive BBL medication independent of high blood pressure has adverse effects on lung function. Beta-adrenergic receptors (β-ARs) play a key role in the regulation of bronchomotor tone . In the respiratory system most of the β-ARs are β2-ARs. However, there are β1-ARs, too, which are responsible for the respiratory effects of cardioselective β1-antagonists. Two systematic reviews suggest that cardioselective BBL do not produce adverse respiratory effects in patients with asthma or COPD [13, 14]. These randomized clinical trials examined only patients with already existing pulmonary diseases and not healthy subjects. Other studies provide evidence that BBL medication, even relatively cardioselective agents, produce bronchoconstriction and thereby worsen respiratory flows in asthmatic patients [10, 16]. Our results indicate that the use of BBL medication is associated with a slight reduction of FEV1 and FVC. Interestingly, the FEV1/FVC ratio was found not to be affected by BBL medication suggesting that the expired volume, FVC, is lowered in proportion. Indeed, the drug-specific effect of BBL medication is more pronounced on FVC than on FEV1. This supports the hypothesis that not airway obstruction, but rather restriction is the more likely mechanism involved in the effect of BBL medication on lung function. For instance, possible effects on the respiratory muscle strength have to be considered. It is well established that beta agonists improve the performance of skeletal muscles  and also positively affect respiratory muscle strength [23, 24]. The opposite effect by BBL medication is suggested by a recent study from Frankenstein et al. performed in patients with chronic heart failure . Thus, we hypothesize that BBL medication may result in a slight reduction of expiratory muscle strength causing a proportional decrease of FEV1 and FVC. However, further studies directly addressing this issue are required.
When reviewing our results, it becomes apparent that from a statistical point of view both high blood pressure and antihypertensive BBL medication have an effect on lung function measurements. But the observed lung function differences between exposed und non-exposed subjects are relatively small, meaning that they have no direct clinical consequence in healthy individuals. However, we could show that among treated but not controlled hypertensive subjects FEV1 had a lower volume of 160 mL compared to subjects with no high blood pressure and no antihypertensive medication. This finding might be of importance on the population level. One possible explanation for this significant lung function reduction might be an additive effect of both treatment and persistent high blood pressure. However, the cross-sectional study design makes it difficult to disentangle the effects of high blood pressure and antihypertensive medication. Thus, it allows only statements about a single point in time and does not allow evaluating the effect of long-standing high blood pressure. Another explanation for this lung function decrement could be that those with persistent hypertension despite medical treatment have a higher underlying blood pressure compared to effectively treated subject. Moreover, the effects of high blood pressure and antihypertensive medication are highly correlated. A detailed analysis of antihypertensive medication indicates that BBL medication and not any other antihypertensive medication is associated with a reduced lung function. This negative effect of BBL medication still remains, when BBL, other antihypertensive medication and high blood pressure are analysed in the same model. Besides, BBL are the most common prescribed antihypertensive medication and it has to be considered that BBL medication might be prescribed for other indications than hypertension, as for example, coronary heart diseases or heart failure, too. This again suggests that the effect of antihypertensive BBL medication on lung function is mainly ascribed to the medicament and not to the indication. Furthermore, a variety of confounders might affect the association between high blood pressure, antihypertensive medication and lung function. Cigarette smoking is a common risk factor for both impaired lung function and high blood pressure and BMI might have an effect on lung function. However, adjustment for these possible confounders did not influence our results. Moreover, we could show that the association was not affected by the concomitance of pulmonary diseases and that the negative effect of BBL medication on lung function is not modified by obstructive lung diseases. This supports our interpretation that BBL have an effect on lung function in the general population. Besides, our results suggest that there may be an effect modification by gender. We could show that in women the percent predicted lung function values did not differ between subjects with and without high blood pressure. Furthermore, the multivariable regression analysis revealed a significant interaction between gender and high blood pressure. This might possibly indicate that high blood pressure has minor effect on lung function in women compared to men.
The large sample size and the population-based setting are a major strength of this study. Furthermore, it is one of few investigations differentiating between the effect of blood pressure and antihypertensive drug treatment on lung function. Nevertheless, this study has some possible limitation. Methodological bias might lead to insufficient lung function measurements. Thus in patients with high blood pressure lung function tests might be stopped earlier, because the respiratory effort might cause an increase in blood pressure. However, we consider this possible bias unlikely to affect our findings. Besides, selection bias might limit the representative status of the population sample included in our analysis. We had to restrict our analysis to subjects aged 40-65 years, because only this age-restricted subset performed lung function tests. However, as this was a random sample, we consider that our population sample is highly representative for this age group of the Augsburg population. Moreover, the cross-sectional study design makes it difficult to make a clear statement about the temporal sequence and causality between high blood pressure, its treatment and lung function. Several prospective studies indicated that high blood pressure is a risk factor for reduced lung function as well as impaired lung function increases the risk for the development of high blood pressure [7–9, 26]. Besides, one has to consider the possible effect of long-standing high blood pressure. For example, subjects with currently normal blood pressure under medication might have had high blood pressure for a long time before it was recognized and treated. Therefore, it is necessary to evaluate the temporal sequence, acute and chronic effects and the causality between high blood pressure, its medical treatment and lung function in further prospective studies.