Discussion
We have evaluated the long-term effect of pregnancy on structural and functional echocardiographic measurements of RV and their association with the number of parity. Although the parameters used for evaluation of RV function had never been measured under the lower reference limit in the study population, these parameters have reduced in some extent. On the other hand, the structural changes of RV were more evident owing to the findings about RV dilation and RV hypertrophy meaning RV basal diameter and free wall thickness were above the upper reference limit. While the number of parities had a significant effect on these functional and structural changes of RV, giving a birth was found as independent risk factor for RV dilation.
The cardiovascular system undergoes several changes during pregnancy in order to supply metabolic demands for both mother and fetus (6). However, the interesting data demonstrated in our study, was the persistency of some of these physiological changes seen in RV after pregnancy and their relationship with the number of parity. The situation can be explained by cardiac remodeling which is defined as basic changes in geometry, wall thickness, size, and ventricular function by means of complex process including a group of molecular, cellular, and interstitial changes (7-10). Although the exact mechanism of cardiac remodeling is poorly understood, the renin-angiotensin system (RAS) is a key mediator involved in the pathogenesis of cardiac remodeling. Activation of RAS is essential for normal pregnancy in order to be able to cope with the increased demand for salt and water during pregnancy. Many studies have shown that in normal pregnancy there is an increase in almost all the components of the RAS. Therefore, irreversible changes in RV dimensions can be seen by means of remodeling related to activation of RAS in pregnancy (11-13). On the other hand, it should be kept in mind that RAS is activated in pregnancy because of maternal physiological demands and in healthy pregnancy it does not result in pathologic processes such as intrauterine growth restriction, preeclampsia etc. This data also can explain why RV dilation and hypertrophy have found in this study without RV dysfunction which are distinct components of RV remodeling (14-16).
The inflammatory process is also responsible for cardiac remodeling (17). While both pro-inflammatory and anti-inflammatory markers increase in pregnancy, a prospective study comparing the inflammatory mediators between late pregnancy and early postpartum, has showed that markers that have predominantly anti-inflammatory effect were higher in pregnancy (18). In addition, some of the autoimmune diseases such as rheumatoid arthritis can ameliorate during pregnancy in line with this prospective study. On the other hand, most of the physiologic changes resolve during the postpartum period in which pro-inflammatory markers are high. Each pregnancy means exposure of this pro-inflammatory postpartum period that may influence RV remodeling and this situation can be the reason of our finding about significant relation between number of parity and RV dilation and RV hypertrophy. Hormonal alterations have important roles in many physiological changes during pregnancy. Estrogen levels gradually increase and reach highest value in late pregnancy. Eghbali et al demonsrated the association between estrogen level and pregnancy-related heart hypertrophy in pregnant rats (19). Indeed this study is very supportive for our finding about association between RV hypertrophy and parity. Whatever the mechanism of cardiac changes during pregnancy, it is obvious that dilation and hypertrophy of cardiac chambers are compensatory alterations against increased plasma volume and cardiac output. Therefore, these changes are necessary for completion of normal pregnancy and the more pregnancy the woman has, the more she will be exposed to this condition. Thus, association between parity and structural changes of RV is reasonable.
According to our study the other independent risk factors for RV dilation were smoking, age and BMI. Indeed, systemic disease especially HT, DM, smoking, increasing age and obesity have negative effect on cardiac remodeling (20-21). In our study population there were neither resistant HT (HT controlled via ≥ 4 antihypertensive drugs) nor complicated DM. This can be the reason why we did not found relation between such diseases and RV dilation. Smoking has structural and functional cardiac effects related to tremendous mechanisms such as hemodynamic and neurohormonal changes, oxidative stress, inflammation etc. Although structural and functional effects of smoking on LV were more studied and well known, in a population-based cohort study, smoking was found independently related to worse RV outcomes (22). From this aspect, our study may give a little contribution to literature even though it was not the main purpose of study. Similarly, obesity has such cardiac alterations either by itself or high incidence of relation with comorbidities such as coronary artery disease, HT, DM. World Health Organization defines overweight and obesity as a BMI over 25 and BMI over 30 respectively. We did not use this classification in study but increasing BMI itself was found as independent risk factor for RV dilation. Again, in line with our study, it has shown in many studies that several structural and functional cardiac alterations are age-related irrespective of comorbidities (23-24).
Although relation between the number of parity and estimated PAP was found statistically significant, there was not any value exceeding 35 mmHg. In fact, transthoracic echocardiography is unreliable method for PAP and overestimates it (25-26). On the other hand, our study may point a linear increase in PAP with increasing number of parity other than causing clinically important outcomes. RA dimensions were also found higher in parous women and it was related to the number of parity. Scarcity of studies about RA and pregnancy makes it difficult to compare, but it can be handled with RV and commentions about RV can be applied to alterations about RA.
Echocardiography is method of choice for assessment of RV. It is widely available and provides useful information about the right heart chambers (27). We have assessed the right heart especially focusing on RV via echocardiography and evaluated the long-term effects of parity on RV and its relation of the number of parities. The studies about the right heart are very few when compared to the left heart and the number of studies declines when it is applied to pregnancy. What makes this study important is its uniqueness indicating the parity had long-term effects on RV and this association has increased in a number-related manner.