1. Introduction
Resting blood pressure (BP) is an independent determinant of left ventricular mass (LVM) [
1]. Conversely, LVM is a common biomarker of heart pathology [
2,
3,
4] and a useful predictor of hypertension development [
2,
5,
6]. Several chronic nutritional and socio-environmental factors affect resting BP and therefore LVM. These include chronic excesses in caloric [
7] or sodium [
8] intake, lack of leisure-time physical activity [
9], and low educational attainment and income [
10]. Additionally, BP is acutely elevated during activities of daily life like exercise, mental tasks/mental stress, cold exposure, and occupational standing [
11,
12]. These acute pressor responses contribute to the stress on the heart and have a cumulative effect on LVM. Therefore, LVM is actually an index of BP over time and in response to lifestyle/socio-environmental stressors [
2]. The factors affecting BP and LVM vary in their level of personal control, but exercise is likely one of the more modifiable factors.
As a modifiable lifestyle factor that influences BP and LVM, exercise is especially appealing because it delivers favorable outcomes on most health parameters and provides the greatest dose–response effect on health at low volumes/intensities [
13]. Regular exercise decreases resting BP and body mass in those with elevated levels, which typically leads to favorable decreases in LVM [
14]. Importantly, habitual exercise decreases resting systolic BP (SBP) more than resting diastolic BP (DBP) [
15], and resting SBP is more closely associated with LVM [
1,
16]. However, during moderate-to-vigorous intensity exercise, the pressures experienced by the heart display a large acute increase and can independently increase LVM [
17,
18,
19,
20] and alter heart function [
21,
22]. Of note, the exercise-induced increases in LVM are typically considered healthy [
21], but may increase linearly with the degree of BP responsiveness during exercise. Thus, it is important to study the BP stresses (e.g., SBP) placed on the heart during exercise as they can be more informative than resting BP alone in those who habitually exercise. Exercising SBP (eSBP) is predictive of hypertension development [
23] and is augmented in adults with a genetically increased risk of future hypertension [
24]. Therefore, young adults who display a high eSBP may develop greater LVM within subclinical ranges. However, an elevated eSBP also suggests they will eventually develop resting hypertension, which will further increase LVM to approach levels of clinical importance. Interestingly, young adults with a genetically increased risk of future hypertension have higher LVM that is not fully explained by resting SBP [
1]. These associations show the importance of answering the following question: does eSBP predict LVM?
Prior research examining the relationship between eSBP and LVM has primarily found a direct association between these variables [
12,
16,
25,
26,
27,
28,
29,
30,
31,
32,
33,
34,
35,
36,
37,
38], but this is not a universal finding [
12,
27,
28,
30,
39,
40]. When examining the results that do not support the association between eSBP and LVM, the participants did not habitually exercise [
12,
27,
28,
30,
39,
40]. Studies which have compared habitual exercisers to non-exercise controls have found a significant eSBP-to-LVM relationship only in the habitual exercisers [
28,
30]. This suggests that exercise promotes greater LVM development in those with greater eSBP only when the exercise stimulus on the heart is routinely applied. Unfortunately, women have often been excluded as research participants [
41], and none of the studies which targeted adults who habitually exercise included women. Because of this, the literature on the relationship between eSBP and LVM in women is less clear, with some showing a significant relationship [
26,
32] and others showing no relationship [
12,
27]. None of the available literature examines how habitual exercise effects this relationship in women.
With the recent cultural shifts promoting women’s fitness as a part of a normal healthy lifestyle, there has been a surge in popularity of resistance exercise for women [
42]. However, none of the prior investigations examining the association between eSBP and LVM examined resistance exercise, regardless of sex. It is possible that this relationship is different when examining resistance exercise as eSBP is greater during resistance exercise compared to aerobic exercise, though it is sustained for less time per session [
43] Further, the stresses placed on the heart during resistance exercise are different than during aerobic exercise (i.e., greater afterload but less volume load). This complicates the applicability of prior research findings when assessing the potential relationship between peak eSBP during resistance exercise and LVM in women participating in regular resistance exercise. Importantly, the relationship between muscular fitness (i.e., muscular endurance via 2 min sit-up test) and LVM has been found to be different in men and women with similar military physical training [
44]. In that prior study, high muscular endurance in men was associated with greater LVM, while this was not the case in women. Therefore, it is difficult to determine what the relationship will be between eSBP during resistance exercise and LVM in women who habitually participate in resistance exercise.
While exercise is unequivocally good for health, these prior studies suggest individuals with exaggerated eSBP responses may warrant special interventions (e.g., modified exercise programs, dietary, or stress management) to prevent excessive LVM development. Without research examining the relationship between eSBP during resistance exercise in resistance-trained women, we cannot appropriately determine needs or best strategies for potential lifestyle interventions. Based on the literature summarized previously, we hypothesized that a direct correlation exists between eSBP during resistance exercise and LVM in apparently healthy resistance-trained women.
4. Discussion
In this investigation, we hypothesized a direct correlation between eSBP and LVM/BSA in apparently healthy resistance-trained women. While the two variables appear to be correlated, the relationship was inversed. Both resting SBP and eSBP were independent predictors of LVM/BSA, but in opposite directions. Higher resting SBP was associated with higher LVM/BSA, and higher eSBP was associated with lower LVM/BSA. When attempting to determine the factors that affected eSBP, there were direct correlations with eTPR, maximal muscular strength (i.e., 1RM), and thus the weight lifted during the set (~70% 1RM). This suggests that high muscular strength, and therefore high absolute training load, resulted in greater eTPR and consequently greater eSBP. Others have recently found exercise BP responses to matched relative exercise loads to be affected by muscular strength (i.e., greater absolute exercise loads in those with greater strength) as well [
55]. It appears likely that in the present investigation greater training loads resulted in greater compressive forces placed on the blood vessels during resistance exercise movements, thus limiting resistance exercise-mediated vasodilation and decreases in eTPR. It should be noted that the weight lifted during the set was not statically independent (
p = 0.060) of LVM/BSA as a predictor for eSBP.
When examining the effect of the variables used to calculate LVM on eSBP, only LVIDd was an independent predictor of eSBP, and it was so with an inverse relationship, suggesting that increased eSBP may lead to a decrease in left ventricular chamber size (i.e., LVIDd). Conversely, resting SBP was not correlated to LVIDd, but was directly correlated to muscle wall thickness (both IVSd and PWTd), leading to a positive association with LVM/BSA. Therefore, our participant population responded differently to SBP during rest and in response to leg extension resistance exercise. Interestingly, women with pathologic aortic stenosis leading to chronic left ventricular pressure overload (experienced at rest and during physical exertion) exhibit exaggerated LVM and shrinking LVIDd compared to males with the same condition [
56]. The decreased LVIDd in women with aortic stenosis, and healthy women from the current study with high eSBP is likely an adaptive function to decrease myocardial work [
57]. According to Laplace’s law, the tension of a spherical wall is proportional to its radius and pressure yet inversely related to wall thickness.
where wall tension ≈ myocardial work, transmural pressure ≈ systolic pressure during the contraction phase of the cardiac cycle, chamber radius ≈ ½ LVIDd, and wall thickness ≈ average of IVSd and PWTd [
58].
Thus, a decreased LVIDd would lower myocardial wall tension/work even in the absence of wall thickening.
In women, low testosterone levels likely decrease the prospect of myocardial muscle thickening. In a 70-day old rat gonadectomy model (i.e., removing endogenous sex hormones) [
59], male rats had a decrease in heart mass, which was partially corrected with 3 mg/day of exogenous testosterone administration. In female rats, gonadectomy did not impact heart mass, nor did subsequent supplementation of estrogen, progesterone, or estrogen + progesterone. Subsequent supplementation with 2 mg/day of testosterone did increase heart mass in female gonadectomized rats. These results, and the results of similar animal investigations [
60], highlight the important role of testosterone in LVM hypertrophy. In human studies, serum testosterone levels correlate with LVM/BSA in older women [
61]. Similarly, exogenous testosterone administration is typically associated with LVM hypertrophy [
62], though this is not a universal finding [
63]. Estrogens provide a complex and incompletely understood set of direct and indirect effects on the myocardium, but generally play a cardioprotective role [
64]. Current understanding suggests that estrogen directly opposes LVM growth due to exercise training using multiple mechanisms [
41]. Therefore, the sex hormone profile of women likely leads to a decreased LVIDd in response to high eSBP instead of increased wall thickness.
Nearly half (n = 15) of the participants in the current investigation displayed concentric remodeling of the left ventricle. This is due to an elevated RWT (normal ≤ 0.42 [
50]; study mean = 0.43 (
Table 1)), which is due to decreased LVIDd. Despite the lack of increased LVM/BSA in this condition, it is believed that this is an early response to left ventricular pressure overload with a trajectory leading to higher LVM/BSA and concentric hypertrophy [
57]. “Physiological hypertrophy” (i.e., healthy hypertrophy) is characterized as an increase in LVIDd and LVM/BSA so that RWT remains normal [
57]. This results from equal adaptation to pressure and volume overload and is common in many types of athletes [
57]. In the current investigation, only women who resistance train regularly (average 3.7 days/week;
Table 1) were included in this analysis, though many also reported regular aerobic training (i.e., primarily volume overload) (average 2.6 days/week;
Table 1). An intervention to increase the aerobic training volume of our participants would likely result in the “physiological hypertrophy” phenotype with preserved LVIDd. Importantly, aerobic training is a potent stimulant for SV improvement, which is limited by concentric remodeling of the left ventricle. Therefore, increasing aerobic exercise may be a useful lifestyle intervention in resistance-trained women with elevated resting SBP and eSBP, as our results suggest these individuals would be at the greatest risk for elevated LVM/BSA and reduced LVIDd (i.e., concentric hypertrophy). This intervention may warrant future research.
While the young, healthy participants of the current investigation likely have minimal cardiovascular risk, with aging, the risk of comorbidities like hypertension increases dramatically [
65]. This will complicate left ventricular geometry, warranting lifestyle interventions such as aerobic training (discussed above) and dietary interventions to prevent the development of concentric hypertrophy. These may include dietary emphasis on proper weight maintenance [
7] and sodium reduction [
8]. Other blood pressure-lowering lifestyle interventional strategies may include stress reduction, adequate sleep, and increased leisure-time physical activity [
9]. These lifestyle intervention strategies are likely impacted by a variety of socio-environmental factors that lead to accessibility issues and other barriers.
The current investigation is not without limitations. We studied young women at low risk of current cardiovascular disease. However, cardiovascular disease risk later in life is a result of behaviors across the lifespan. Therefore, it is important to study the early effects of lifestyle choices to better understand how they may impact risk later on. The emphasis of this investigation was on LVM/BSA, which typically becomes dangerous when hypertrophic cardiomyopathy is present. The dogma in the past 30 years for this condition has been that it is a genetic disease rather than a lifestyle disease. However, recent evidence suggests a non-genetic lifestyle component of the disease, as most with the condition test negative for known genetic mutations, and many with these genetic mutations do not develop the condition [
66]. Regardless, a high eSBP suggests an increased likelihood of future hypertension. Thus, studying the physiology of young individuals likely to develop pathology later in life is important for characterizing the development of the pathology in its subclinical stages. Additionally, we found that elevated eSBP is associated with decreased LVIDd in young adulthood, which may be complicated later in life when resting blood pressure begins to reach clinically significant levels. Our study sample did not just perform resistance exercise. Therefore, some effects of aerobic exercise likely confound our data. However, there is a strong bias towards resistance training in our sample as the participants completed nearly double the minimum recommended resistance exercise frequency according to the American College of Sports Medicine but did not reach the minimal recommended aerobic exercise frequency. Extensive training histories of the participants were not recorded. Therefore, conclusions regarding training experience (e.g., months or years) or resistance training focus (e.g., muscle power vs. local muscular endurance) cannot be determined. However, resistance training characteristics (e.g., sets, repetitions, movement speed, etc.) usually change over time and vary person-to-person at any one point in time, likely limiting the usefulness of such data in a heterogeneous group. Likewise, we did not collect data on some potentially confounding variables such as socio-economic status, aerobic fitness level, activities of daily living, nutritional intakes, etc. Future studies should determine the modulating impact of these and other confounding variables. The current investigation has a cross-sectional study design, limiting mechanistic insight. However, the mechanisms discussed here are supported by other experimental studies in varying populations and different stress-inducing protocols. Despite this, the authors believe longitudinal testing should be performed to confirm the findings of this investigation. Additionally, cross-sectional studies comparing populations with different sex hormone profiles (e.g., healthy resistance-trained women vs. men) would help to support the proposed mechanisms of this investigation. Therefore, blood biomarker analysis should be conducted in future studies to assess testosterone, estrogen, serum myostatin levels, and other markers of hypertrophy. The current investigation utilized a widely used and validated [
51] research technique of non-invasive finger photoplethysmography to continuously monitor blood pressure during the resistance exercise bout. This technique is not perfect, and could have modified our results as it assesses finger blood pressure rather than the standard brachial artery blood pressure. This is important as blood pressure values vary throughout the vascular network [
67,
68,
69]. We attempted to address this by level-correcting the resting finger blood pressure values to resting brachial artery blood pressure values. Finger blood pressure monitoring can also result in errors in blood pressure values when the hand being assessed is not fully relaxed [
51]. A single researcher assessed the blood pressure tracings of every participant and excluded participants whose signals included significant error.