Obesity is recognized as an important contributor to heart failure and cardiovascular disease (CVD) independent of comorbid illnesses [1‐3]. The increase in body weight and composition was thought to be associated with the changes in left ventricular (LV) structure, attributable to increased hemodynamic load and a cluster of altered inflammatory and metabolic state [4‐6]. It has been well documented that chronic volume load in response to obesity exhibited increased LV mass and cavity size, resulting in eccentric left ventricular hypertrophy (LVH) [7, 8]. Likewise, concentric LVH characterized by an increase in LV wall thickness (LVWT) greater than the chamber radius and elevated mass-to-volume ratio, was largely related to the impact of excess adiposity [4, 8‐10]. Given that being the precursor for worsening cardiac function, LV structural abnormalities impose an elevated risk for progression of symptomatic heart failure and are considered as a powerful, integrated predictor of cardiovascular morbidity and mortality [11‐13]. On this basis, it is now becoming evident that the effect of obesity on LV remodeling offers a conceivable pathophysiologic explanation for the relationship of excess body fat with adverse cardiovascular outcomes. Determining which measure of adiposity and obesity contributes to the changes in LV geometry could promote early identification and prevention of cardiovascular events.

There is a diverse geometric pattern of left ventricle adaptations to fat distribution, in view of adipose depots inherently involve disparate metabolic process, structural composition, and functional manifestation [14]. In this context, a sample of 1073 young individuals from Bogalusa Heart Study revealed that increases in body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) were demonstrated to have independent influences on the development of eccentric LVH but not concentric LVH [15]. Interestingly, in a multiethnic cohort of 1262 adults from the Dallas Heart Study, the predominant impact of general or central adiposity on LV phenotype was concentric remodeling without additional ejection fraction change [16]. The notion that visceral adipose tissue, an index of central adiposity, was a key independent determinant of LV concentricity and unfavorable hemodynamics has been recently arisen from two observations [17, 18]. These findings placed particular emphasis on the potential role for adiposity and its distribution in LV morphology, accounting for the pathogenic correlates of future heart failure.

Lipid accumulation product (LAP) is an emerging central lipid accumulation parameter in the light of taking both waist circumference (WC) and triglyceride (TG) levels into account, with prior studies reporting its strong predictive of clinical cardiovascular consequences and all-cause mortality [19, 20]. Lately, a novel parameter, named cardiometabolic index (CMI), has been put forward by Ichiro Wakabayashi to adequately discriminate the presence of diabetes and atherosclerotic progression [21‐23]. It represents a combination of TG/ high-density lipoprotein cholesterol (HDL-C) ratio and WHtR, highlighting the product of them integrates the blood lipid and abdominal obesity into a clinically accessible and conceptually appealing marker. Of note, CMI could be clinically relevant with respect to the LV geometry, with insulin resistance and carotid intima-media thickness (IMT) having a substantial effect on cardiac remodeling [24, 25]. However, none of the studies that address the impact of measures of adiposity (CMI and LAP) on the pathogenesis of abnormal LV geometry has been specifically established. In effect, the gender difference in fat quantity, anatomic storage and consequent hemodynamic influence has been proposed to drive a better understanding of the link between obesity and LV remodeling. Accordingly, the aim of this study was to provide further insight into exploring CMI and LAP as a reliable biomarker for gender-specific identifying those subjects at higher risk for LV geometry in general population of rural China.

Novel findings in our study include an outstanding gender difference in the positive correlation of adiposity indices (CMI and LAP) with elevated likelihood for LV structural abnormality among the general Chinese population. The greater degree of eccentric and concentric LVH seen in obesity in response to increasing CMI and LAP is not only irrespective of conventional cardiovascular risk factors but is also pronounced in females than males, suggesting that excess adiposity per se influence abnormal LV geometry substantially more in females. Confirming CMI and LAP as a key independent determinant of LV hypertrophy and geometry had crucial implications for exploring potential areas of future investigations targeting CMI and LAP gender-specifically to prevent or weaken the effects of LV remodeling on heart disease.

Early data pointed out that due to a state of chronic volume overload, the prime effect of obesity on LV structure has been considered as eccentric LVH, with a resulting parallel increases in LV cavity size and LVWT and no alteration in RWT [7, 8, 34]. Instead, the results of recent studies consistently advocated a concentric pattern to be linked with increased weight, in nature with a greater extent increases in LVWT as compared to LVIDD accompanied by an increased RWT [4, 10, 35]. The majority of prior works evaluating the adverse impact of adiposity on LV geometry have mainly focused on parameters of general obesity such as BMI. The implication of BMI on eccentric LVH, represented by higher LVEDV, and concentric LVH geometric pattern, expressed by increased LVM/volume ratio, has been previously demonstrated in a cross-sectional fashion [4, 36]. A growing body of evidence supports the prognostic value of long-term change in BMI on certain aspects of LV geometry. Two researches from the Framingham Heart Study, performed in middle-aged adults, suggested that longitudinal tracking of LVWT, RWT and LV dimensions increased progressively with BMI over a 16 years period [37, 38]. Notably, in a Coronary Artery Risk Development in Young Adults (CARDIA) study, increasing BMI longitudinally over 25 years contributes to LV structural remodeling assessed by larger LV volume, greater LVM/height, and LVM/LVEDV ratio [39].

BMI has been the subject of numerous previous studies to interpret the influences of obesity on cardiovascular risk, while it was reported to be insusceptible to make a distinction between the excess adipose tissue and heavy muscle mass. It is now clear that body fat distribution, especially central adiposity, is believed to provide additional information than sheet quantity of body fat [40, 41]. The prospective cohort Atherosclerosis Risk in Communities study (ARIC) noted that greater metric of abdominal obesity, defined by WC, constituted an independent risk factor for subclinical abnormalities in LV structure [42]. In contrast to a recent study from Bogalusa Heart Study in which an eccentric LVH but not concentric LVH was predominant for WC [15], the Dallas Heart Study and a report from South African community proposed that WC raised considerably the possibility of concentric LV remodeling phenotype, which is prognostically worse due to a high risk for cardiovascular death [10, 16]. Furthermore, there have discrepant conclusions concerning the malefic health consequences of visceral adiposity index (VAI) as a valid estimate for the prediction of LV remodeling and geometry. Current investigations of LV morphology have elucidated that individuals with more visceral adiposity predisposed to greater LVM/volume ratio and LVWT concurrent with a decrease in LVEDV, which represented the summation of multiple diverse aspects of concentric LV remodeling [17, 18]. Conversely, Hu T and colleagues failed to support long-term increases, in both magnitude and velocity of VAI, as a marker associated with abnormal LV geometry [15]. Hence, it would be useful to embark on a novel and easily assessed marker of abdominal adiposity in clinical practice to stratify the risk of divergent cardiovascular structural and hemodynamic phenotypes given the paucity of efficient diastolic heart failure therapies.

It is noteworthy that LAP, which is computed from WC and fasting TG, has offered mechanistic insight into worse cardiometabolic profile given its independent relationship with incident cardiovascular events [19, 20, 43], yet is not quantified in the clinical setting of abnormal LV geometry. At present, CMI, a product of TG/HDL-C ratio and WHtR, has the advantage of being applicable in the assessment of diabetes and atherosclerotic progression [21‐23]. Ichiro Wakabayashi et al. reflected that contribution of elevated levels of CMI to the prevalent diabetes risk was somewhat stronger in females than in males [22]. A relevant study further expanded current knowledge by confirming the importance of central adiposity (by CMI) as a potential etiology of atherosclerotic progression (by IMT) in subjects with peripheral arterial disease [21]. Given the fact that diabetes and atherosclerosis have been the primary mediators of subclinical LV remodeling, it is likely that CMI could explain the adverse cardiovascular effects of central obesity [24, 25]. In this sense, this middle-aged, cross-sectional, population-based design is initiated to examine and validate the practicality of CMI and LAP as the key correlates of LV geometric abnormalities in rural China.

Our data underlined the clinical value of new central adiposity measures such as LAP and CMI in assessing the risk of LVH which differed somewhat by gender. There was a greater detrimental influence of CMI on abnormal LV morphology in females compared with males. Our findings were coherent with those of previous clinical studies in that obesity was proved to elicit a cluster of LV geometric abnormalities, which is especially evident in females. A community-based sample of the MONICA Augsburg cohort described that the rise of LVH prevalence in response to obesity and hypertension was generally higher in females [44]. In keeping with this, a large, biracial cohort of elderly participants speculated that obese females, but not males, were significantly accompanied by abnormal LV geometry [42]. In the 2919 members of the Strong Heart Study cohort, increased LV mass was a function of ascending waist-to-hip ratio, a typical index reported in the context of central obesity [45]. There was a further demonstration that females, in whom adipose tissue was much more abundant, denoted excess LV mass substantially greater than males. In our study, the statistical effect of visceral distribution on the variability of LV mass in females was indicated by the significant impact of CMI and LAP. At each BMI-level, the greater degree of adipose tissue in females provides an explanation for this differential response [46]. A considerable proportion of females possess a higher percentage of body fat than males, which may in turn expose them to central obesity [47]. In addition, as the average age of females in our study was 53.39 years where sex hormone levels have declined, the favorable cardiovascular effects of estrogen were inevitably disappeared. Owing to the fact that estrogen is believed to inhibit cardiac hypertrophy and testosterone promotes LV hypertrophy, endogenous sex hormone differences might account for gender difference in obesity-related LV remodeling [48]. On the other hand, central obesity can cause dramatic changes in the release of inflammatory markers [49], which is the major driving force for regulating cardiac energy metabolism [50]. It is well known that as for normotensive obese females, pro-inflammatory cytokines have been implicated in both echocardiographic abnormalities and the amount of visceral adipose tissue [51]. Obesity and female gender interacted in determining myocardial glucose uptake and insulin sensitivity, which demonstrated gender-related differences in the myocardial substrate metabolism due to obesity [52].

There has been a great interest in exploring the underlying mechanism regarding the potential adverse impact of CMI and LAP on morphologic LV abnormalities. The cardiac workload in visceral obesity is constantly increased, probably as a consequence of supplying the high energy demands of the adipose tissue [53, 54]. An increase in LVM might be the result of chronic volume overload and insufficient adaptation of peripheral resistance to the increased cardiac output, characterizing a state of increased stroke work [54]. Secondly, central fat distribution, which has been assumed to be the metabolically active compartment of fat deposits, could mediate increased LVM through the effects of expression of circulating inflammatory cytokines, elevated availability of angiotensinogen, and increased myocardial fibrosis [53, 55]. Pro-inflammatory visceral adipocytes generate a cascade of neuro-hormonal signals, which play a critical role in insulin resistance and cardiac remodeling [56, 57]. Also, the crucial importance of hyperinsulinemia and insulin resistance in favoring myocardial hypertrophy is well recognized in the context of growth-stimulating effect of insulin or expansion of blood volume [58]. Thirdly, exposure of the heart to deposition of fat tissue and the presence of high fatty acid and TG levels in the myocardium impair cardiac structure and induce an increase in LVM [58, 59]. Moreover, superimposing higher systolic blood pressures to obesity combines hemodynamic (pressure, volume overload) and non-hemodynamic stimuli (fat infiltration, inflammation), which together has an additive effect on concentric myocardial remodeling [60].

Our results from this study are subject to some limitations. First, the cross-sectional design allows for only determining an association of CMI and LAP with abnormal LV geometry, but no potential cause-effect relationships can be drawn. Further confirmations in prospective studies to assess the prognostic role of CMI and LAP in LV morphology are warranted. Secondly, more detailed and precise imaging phenotypes of adiposity tissue distribution such as visceral or abdominal subcutaneous fat are not available in our study. Thirdly, our sample is comprised of only Chinese adults, and it is unknown whether our findings are also applicable to other racial or ethnic populations. Notwithstanding these limitations, the potential public health implications for the prevention and treatment of LVH and heart failure also merit comment. Our population-based design (which permits extensive multivariable adjustment for several confounders) for the first time acknowledges that CMI and LAP have a fulfilling supplementary beneficial effect on predicting LV geometric pattern in a large sample of community members of Northeast China. Within the scope of the epidemiological study, CMI and LAP are much more cost-effective and clinically feasible parameter to evaluate obesity-related pathologic cardiac remodeling when compared with quantitative measurements of visceral fat from advanced imaging. Under this scenario, cardiovascular risk stratification might be improved by adoption of simple central adiposity measures (defined by CMI and LAP).

Females with greater CMI and LAP were more likely to lead in eccentric and concentric LVH with a concurrent decrement in their associations among males. Given the gender differences in LV adaptation to adiposity exists, our results add further impetus to translating CMI and LAP into a clinical and public health recommendations for reducing the burden of LVH. Efforts to target individuals at higher cardiometabolic risk on a gender-specific basis, integrating assessments of CMI and LAP may prevent abnormal LV geometry and incident heart failure.