Increased western diet consumption combined with a sedentary lifestyle drives the global prevalence of being overweight and having obesity (1). While previously mostly seen in aging populations, today younger populations are more frequently affected (2). Consequently, the onset of both hypertension and type 2 diabetes (T2D) is also shifting to younger age groups (3, 4), subsequently increasing cardiovascular disease prevalence (5).

Non-ischemic cardiomyopathy is the most frequent cause of sudden cardiac death in the young, whereas the prevalence of ischemic cardiomyopathy increases with age (6). Young adults with non-specific cardiovascular symptoms are therefore often referred for MRI to rule out non-ischemic cardiomyopathy (7). Pathological cardiac MRI findings include left ventricular hypertrophy (LVH), chamber dilatation, and decreased ejection fraction (EF) (8). Early changes in cardiomyopathy are subtle and could overlap comparable alterations in overweight, hypertension, and T2D (9). Large cohort studies in mature adults (mean age, 55–62 years old) show overweight to be independently associated with increased LV mass and cardiac volumes, hypertension with increased LV mass, and T2D with smaller volumes (10–13). As included populations were asymptomatic and free of cardiovascular disease, the aforementioned alterations can be considered risk factor-related cardiac adaptation. To our best knowledge, the impact of these risk factors in younger adults has not been demonstrated yet.

Quantitative myocardial tissue characterization has an increasingly complementary role in the diagnosis of non-ischemic cardiomyopathies (14). For example, cardiomyopathies featuring myocardial fibrosis or edema show respectively prolonged native T₁ and T₂ mapping values (15, 16), and in some cases, also increased extracellular volume (ECV) (17). In high-risk populations, these mapping values could be different, which should be taken into account to avoid misdiagnosis. In athletes, for example, native T₁ and T₂ mapping and ECV have already been described to be discriminative for the athlete's heart and cardiomyopathy (14, 18). Previous studies in mature hypertensive populations have reported higher native T₁ values and ECV in presence of LVH (19), however, as these increases were smaller than seen in patients with hypertrophic cardiomyopathy (HCM), these markers may serve as potential discriminators (20). In mature patients with T2D, ECV was mainly higher without clear changes in native T₁ values (21). In both younger and older adult obese populations, no differences were reported in native T₁ values and ECV (22, 23). T₂ mapping values have only been reported in mature hypertensive and T2D subjects, both show higher values than in healthy controls (24, 25).

The aim was to investigate the impact and possible combined effects of overweight, hypertension, and T2D on cardiac morphology, function, and tissue characteristics in an asymptomatic young adult population.

In this cross-sectional cardiac MRI study, we demonstrated that cardiovascular risk factors in an asymptomatic young adult cohort are associated with subclinical cardiac alterations. Substantial variation in LV mass, LV mass/volume ratio, cardiac volumes, ECV, and T₂ values was explained by independent clinical variables related to overweight, hypertension, and T2D. Variation in EF and native T₁ values, however, was explained to a lesser extent.

With multivariate regression analysis, we showed that increased BMI, SBP, and HbA1c are independently associated with higher LV mass in young adults. The independent linkage of BMI and SBP on LV mass caused by respectively volume and pressure overload was in agreement with previous cardiac MRI findings in mature adult populations (age range, 41–85 years) (10–12) and an echocardiographic study in adolescents (mean age, 16 ± 2 years) that reported increasing LV mass with increasing blood pressure (34). The positive association between HbA1c and LV mass was in line with results in mature study cohorts (11, 35), but also with echocardiographic findings in young adults (mean age, 27 ± 7 years) (36). In the current study, risk factors explained less variation in LV mass compared to studies in mature populations (age range, 45–85 years) (10, 11). This difference might be age-related, as young adults are more likely to be exposed to these risk factors for a shorter period. Furthermore, in asymptomatic mature populations, increased LV mass is linked with heart failure events (37). This deleterious effect of increased LV mass could also occur in the growing young adult risk population, possibly worsening when conditions remain unchanged later in life.

Cardiac and SVs were significantly associated with BMI, waist-hip ratio, blood pressure, and HR, while associations with HbA1c were less obvious. In previous studies, being overweight was linked to chamber dilatation with BMI as an independent predictor (10–12, 38). Although BMI is the gold standard to define overweight, it does not reflect on the actual body fat distribution which strongly correlates with cardiovascular risk, therefore we also included waist-hip ratio as an independent variable (39). As expected, increased BMI was associated with higher cardiac volumes, but surprisingly, a higher waist-hip ratio was associated with lower cardiac volumes and increased mass/volume ratio. These results confirm that especially central body fat deposition is associated with adverse concentric remodeling (40). We also found that cardiac volumes are lower with increased HR, confirming results in a previous study (38). Another study hypothesized that increased resting HR contributes to initial cardiac remodeling, requiring smaller cardiac volumes, and this possibly also applies to our young population (41). The opposite effect of SBP and DBP on end-diastolic and SVs was also in concordance with previous findings in mature populations (10–12). In this study, HbA1c only showed a positive association with RV volumes, while no impact on the LV was found which confirmed findings in a previous study in young T2D subjects (aged 32 ± 7 years) that only examined the LV (4). In mature populations, however, T2D was associated with smaller LV and RV volumes (10, 11), suggesting that the impact of T2D on cardiac volumes could be age-related. As the aforementioned alterations in cardiac dimensions can overlap early findings in dilated cardiomyopathy, these need to be considered in imaging diagnostics (9).

The full models for LV and RV EF only explained respectively 5 and 20% of the existing variation. These low percentages, combined with the substantially higher explained variation for RV relative to LV function, confirmed regression models previously reported in mature populations (10–12). Similar to these studies, we showed that overweight-related variables had no impact on the EF (10–12). We also showed that SBP had a positive association, while DBP and HbA1c were negatively associated with EF. These results are in line with findings in older adult populations, suggesting that hypertension and T2D cause subclinical systolic changes irrespective of age.

To our best knowledge, this is the first study that explained variation in myocardial tissue characteristics (including T₁, T₂, and ECV) using multivariate regression analysis with cardiovascular risk factor-related predictors. BMI showed a significant association with native T₁ values, while previous studies showed similar T₁ values in both overweight (aged 41 ± 13 years) and obese subjects (aged 32 ± 7 years) relative to normal weights (22, 42). Comparable to our results, T2D populations had similar T₁ values relative to controls (21). Previous studies reported increased T₁ values in hypertensive subjects with LVH (15). We found no such association, which is probably related to the relatively small LV mass increase in our hypertensives.

Current results indicate that increased BMI and blood pressure are associated with reduced ECV, suggesting hypertrophy of myocytes similar as seen in athletes (43). Conversely, ECV is often increased in non-ischemic cardiomyopathies (14). ECV could therefore potentially discriminate adaptations associated with overweight, obesity, or hypertension from early pathology, such as previously suggested to distinguish the athlete's heart from HCM (20, 44). The positive association between HbA1c and ECV was in agreement with findings in subjects with T2D (21). Increased ECV is linked to heart failure (45), underlining the importance of its early recognition.

Heart rate was the most significant negatively associated predictor of T₂ values. This can be explained by the nature of the T₂-prepared SSFP sequence, which can produce incomplete T₁ relaxation during increased HRs, influencing T₂ values (46). Individuals with cardiovascular risk factors often have increased HRs, as confirmed in the current study (31). Using standard T₂-prepared SSFP sequences could therefore result in underestimation of true T₂ values in these populations, which needs to be taken into consideration (28).

Increased SBP was the only other independently associated predictor of (lower) T₂ values. Our findings confirm similar T₂ values reported for normal-weight and overweight subgroups (age 41 ± 13 years) (42), however, they are in contrast with studies reporting higher T₂ values in T2D populations (aged 56 ± 12 years) and hypertensives with LVH (aged 54 ± 16 years) (24, 25). Most likely, in the latter group, higher T₂ values are caused by the used scanning techniques, FLASH, which is not susceptible to HR effects. Discrepancies might be explained by longer exposure to risk factors causing T₂ alterations similar to those found in non-ischemic cardiomyopathies (16).

In summary, we showed in an asymptomatic young adult population that sedentary lifestyle-related risk factors are associated with subclinical cardiac alterations on MRI, and this needs to be considered in clinical decision-making. These findings are also comparable to studies in more mature populations, which already demonstrated that subclinical cardiac alterations are associated with long-term adverse cardiac events. If current trends in risk factor prevalence keep rising, this may cause additional cardiovascular disease burden, especially in Westernized countries.

The original contributions presented in the study are included in the article Supplementary Material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by Medical Ethics Committee of the University Medical Center Groningen (no. 2016/476). The patients/participants provided their written informed consent to participate in this study.

VD, RD, BV, and NP conceptualized the study. GS, MB, KH-O, and NP drafted the manuscript. GS, MB, RB, and NP contributed in data acquisition. GS and NP interpreted the data. RS, RD, and NP supervised the project. RD, RB, and NP were responsible for resources. RS, VD, CN, DS, and BV were responsible for review and editing. All authors approved the submitted manuscript.

This work was supported by the Dutch Heart Association (2016T042).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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