Echocardiographic left ventricular geometry profiles for prediction of stroke, coronary heart disease and all-cause mortality in the Chinese community: a rural cohort population study

Left ventricular (LV) remodeling can be defined as the process of LV structural change in response to alterations in intrinsic myocardial tissue feature and architecture, or to external stimuli caused by increased pressure or volume overload [1]. Echocardiography that is easily accessible, inexpensive and quick makes possible the recognition of specific LV geometry. In light of LV mass and wall thickness, four echocardiography-derived geometric patterns, including normal geometry, concentric remodeling, concentric hypertrophy and eccentric hypertrophy, are proposed to explain the pathophysiologic basis for cardiac remodeling [2]. The hypertrophic cardiomyopathy and systolic pressure load imposed on LV by hypertension or aortic valve stenosis frequently result in concentric remodeling or hypertrophy, whereas diastolic volume overload imposed on LV in dilated cardiomyopathy, coronary heart disease (CHD), and mitral or aortic regurgitation generally leads to eccentric hypertrophy [3]. Irrespective of etiology, abnormal LV geometry is considered a valuable echocardiographic phenotype that reflects the severity and chronicity of cardiovascular risk factors, suggesting their potential to offer better prognostic information than traditional ones [4‐7]. In this regard, the contribution of LV geometry to clinical prognosis has been extensively explored in a variety of cardiovascular disease (CVD) settings.

A number of epidemiological studies demonstrated that LV geometric changes predisposed individuals to increased risk of unfavorable CVD outcomes, including heart failure, cardiac arrhythmias and cerebrovascular disease [8‐11]. Conversely, Tovillas-Moran et al. found that the incidence of major adverse cardiovascular events (MACEs) was similar in the four geometric pattern groups, and there was no significant evidence for an association between LV geometry and MACEs in hypertensive patients [12]. It should also be noted that, within subtypes of LV geometry, there is disagreement between studies as to which pattern is the most predictive. Although most population studies have consistently linked LV concentric hypertrophy with poor outcomes [4, 13‐15], the reports regarding the adverse impact of LV concentric remodeling and eccentric hypertrophy on prognosis are conflicting [16‐18]. Until now, most researches have been restricted to European or American populations and often are quite limited in sample size. However, there is a paucity of data on the possible link between abnormal LV geometric patterns and incident adverse outcomes in Asians. Additionally, the prognostic implications of echocardiographic LV geometry in predicting both cardiovascular events and all-cause mortality are incompletely understood, especially in the general population. And few studies have investigated sex-related influence of LV geometry on the prediction of clinical poor outcomes.

Hence, the purpose of this large-scale epidemiological follow-up study was to assess the overall and sex-specific prognostic significance of different LV geometric patterns by echocardiographic measures for incident stroke/CHD and all-cause mortality in a general Chinese population.

To the best of our knowledge, this is the first study to investigate the predictive influence of LV geometric patterns on the risk of adverse outcomes in a general Chinese population of nearly ten thousand with a median follow-up of 4.66 years. The major finding of current cohort is that abnormal echocardiographic LV geometry may be an independent and incremental prognostic factor for stroke/CHD and all-cause mortality, and there are some sex differences in the relation between LV geometric patterns and adverse outcomes. Our results may help augment the understanding of LV remodeling-associated stroke/CHD risk and sudden death in clinical practice.

Given that the plasticity of LV remodeling is influenced by differences in adverse stimuli and exposure duration to risk factors, and involves structural, metabolic and functional maladaptive alterations, it is biologically plausible that abnormal LV geometry may add prognostic information for cardiovascular risk [29]. Although LV geometric abnormality has been reported to have a notable prognostic importance and be associated with unfavorable cardiovascular outcomes [4, 8, 17], the contribution of different geometric subtypes to CVD and all-cause death risk is debated [30, 31]. In most population-based prospective studies, LV concentric hypertrophy has been confirmed to carry the greatest risk of future cardiovascular morbid events or all-cause mortality in patients with hypertension, myocardial infarction, AF or ischemic stroke [2, 32‐34]. Our cohort demonstrated that LV concentric and eccentric hypertrophy were independent risk factors for both stroke/CHD and all-cause death incidence, while LV concentric remodeling was only associated with the risk of incident stroke/CHD in total population. There are several explanations that may underlie our findings. First, hemodynamics, neurohumoral activation, oxidative stress, coronary microcirculation dysfunction and inflammation implicated in the pathophysiology of LV remodeling are possible links between abnormal LV geometry and adverse cardiovascular events [32]. Second, hypertension plays an essential role in the progression of LV hypertrophy and cardiac-cerebral vascular disease [7, 10, 35]. Third, concentric remodeling is earliest change and a compensatory adaptation to LV systolic pressure overload, but concentric and eccentric hypertrophy have an association with the greater LVMI, which is a marker of more advanced end-organ damage and a leading risk for CVD morbidity and all-cause mortality [9]. In addition, LV remodeling causes LA enlargement, which is a significant predictor of adverse cardiovascular events [36]. Taken together, echocardiographic LV geometry as a key parameter has important implications for enhancing risk stratification and prediction. The early control and reversal of LV remodeling, especially concentric and eccentric hypertrophy may be a therapeutic target for decreasing future adverse events. However, further researches need to explore the mechanisms responsible for cardiac geometry-induced poor outcomes and investigate an effective way to improve prognosis in the general population with LV geometry change.

Based on 8848 hypertensive patients from the Campania Salute Network, de Simone et al. found that LV concentric and eccentric hypertrophy were associated with a marked increase in major cardiovascular risk, whereas no significant risk was detected for LV concentric remodeling [13]. In the Prospective Study of the Vasculature in Uppsala Seniors study, a 2.3-fold increased risk of future CVD was seen for LV concentric hypertrophy as compared to normal group, but LV concentric remodeling and eccentric hypertrophy were not associated with an increased risk of CVD in elderly individuals without myocardial infarction [14]. By assessing all-cause mortality in hypertensive patients, Milani et al. found a significant link between abnormal LV geometry and increased risk of all-cause mortality when compared to normal geometry, and mortality was elevated 2.0-fold in LV concentric remodeling, similar to eccentric hypertrophy [37]. A cohort study in New Zealand reported that LV concentric remodeling and eccentric hypertrophy were independently associated with higher all-cause mortality in people of advanced age [38]. However, our general population-based study found no significant results with respect to the ability of LV concentric remodeling to predict all-cause mortality. A consistent findings were observed in the Losartan Intervention for Endpoint Reduction (LIFE) echocardiography study, Bang et al. demonstrated that LV concentric and eccentric hypertrophy, but not concentric remodeling, were relevant to an increased risk of all-cause mortality in hypertensive patients [15]. A possible explanation for above discrepancy may be attributable to differences in study cohorts, including population selection, sample size, disease type, reported outcomes, follow-up length and ethnicity [12, 35].

Furthermore, current study examined the prognostic relevance of geometric patterns in sex-specific subgroups. After adjusting for the potential confounders, the association between LV eccentric hypertrophy and stroke/CHD incidence was revealed in men, whereas in women, LV concentric hypertrophy was associated with both incident stroke/CHD and all-cause mortality, and eccentric hypertrophy was related to all-cause mortality. These results suggested that echocardiographic predictors of adverse outcomes might differ between men and women, favoring the due consideration of sex-dependent influence in the risk prediction tool. In a prior report, Framingham investigators observed that LV concentric hypertrophy was associated with an increased risk of death and incident CVD in preselected healthy people, particularly in men [17]. In a recent prospective study with 3754 CHD patients, Miller et al. illustrated that LV concentric hypertrophy was correlated with elevated all-cause mortality in both women and men, while eccentric hypertrophy was to increase the risk for all-cause mortality in women but not in men [39]. The reasons for these sex differences in the adaptation of LV remodeling to develop into different outcomes are not clear, but different responses to the same stimuli and altered compensatory pathways in men and women have been demonstrated [10, 39]. In extent, the sex differences may be attributed to sex differences in applicability of the European definitions for LV remodeling on Asian cohorts. Additional pathophysiologic studies are warranted to elucidate the mechanisms underlying these sex-specific associations.

Several limitations exist in our study. First, this was a single center study and some participants were excluded due to a lack of ultrasonic data, which perhaps resulted in a selection bias. Second, we used European definitions on Asian population because of the lack of echocardiographic definitions of LV remodeling profiles for Asians. Third, although we tried to adjust for potential risk factors, there might be residual confounding. In addition, the limited number of end events in this study might restrict the interpretation of results. Therefore, further longitudinal studies involving larger and multiethnic samples with longer follow-up time are warranted to confirm our observation.

Overall, abnormal echocardiographic LV geometry carried a significant increase in the risk for stroke/CHD and all-cause death incidence. LV eccentric hypertrophy was associated with an elevated risk of incident stroke/CHD in men, whereas concentric or eccentric hypertrophy had an association with the incidence of stroke/CHD or all-cause mortality in women. Thus, the efforts should be made to emphasize the importance of preventing LV remodeling in order to reduce future adverse events in the general population.