Global longitudinal strain (GLS) is a sensitive measure for detecting early cardiac dysfunction, but prone to variability by age, race/ethnicity, and sex. To date, GLS has not been described in Hispanics/Latinos, nor has GLS been associated with heart failure risk factors. Data from the Echocardiographic-Study of Latinos, a population-based study of Hispanics/Latinos in the United States, was used. A reference healthy sample was used to define the 95th-percentile lower limit of normal GLS value of–14.2% which was applied to the target population to describe the distribution of GLS across age, gender, and Hispanic/Latino background groups. The proportion of normal/abnormal GLS and left ventricular ejection fraction are described, as well as the proportion of abnormal GLS across prevalent heart failure risk factors (hypertension, obesity, and diabetes). Survey statistics and weighted frequencies were used in all analyses. The study sample consisted of 1,818 adult participants (mean age 56.4 years; 42.6% female). The overall ECHO-SOL target population had a mean GLS of–17.6% with 12.1% having prevalent abnormal GLS. GLS was significantly worse in men than women, and abnormal GLS was more prevalent among individuals of Cuban background than any other Hispanic/Latino background group. More than half (56.4%) of individuals with abnormal GLS had values within the normal left ventricular ejection fraction range, and there were worsening GLS values with increasing heart failure risk factor burden (p < 0.01). In conclusion, our study establishes the first Hispanic/Latino-specific GLS reference values, emphasizing the importance of representative populations in the derivation of myocardial deformation thresholds. Abnormal GLS was prevalent among Hispanics/Latinos, and increasing heart failure risk factor burden correlated with worsening GLS, reinforcing the role of risk factors in early cardiovascular risk assessment.
Myocardial deformation metrics are influenced by patient-specific characteristics and risk factors. Hispanic/Latino individuals are the largest minority group in the United States (US), comprising 19% of the population and projected to approach 30% by 2060. Despite evidence that Hispanic/Latino individuals experience a higher burden of cardiovascular disease, , no population-based studies have characterized the distribution of global longitudinal strain (GLS) measured by speckle-tracking echocardiography (STE) in this group. GLS is a well-validated measure of global and regional ventricular function that detects subclinical myocardial dysfunction beyond traditional 2D imaging. ,, GLS outperforms conventional echocardiography for predicting adverse events and risk stratification, ,,,, and its use has expanded to clinical conditions such as cardiovascular disease, , heart failure, chemotherapy cardiotoxicity and hypertensive emergencies. , GLS also offers greater prognostic value than left ventricular ejection fraction (LVEF) in heart failure, and may be useful in screening, monitoring, , and tailoring of treatment. , The present study utilized a large population-based cohort of Hispanic/Latino adults to: (1) describe the distribution of GLS, (2) evaluate differences by sex, age, and Hispanic/Latino background group, (3) compare normal and abnormal GLS with LVEF, and (4) examine abnormal GLS across increasing heart failure risk factor burden (obesity, hypertension [HTN], and type 2 diabetes mellitus [DM]).
Methods
The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a comprehensive population-based multi-center (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA) longitudinal cohort study ( N = 16,415 and mean age 43 years) of Hispanic/Latino individuals aged 18 to 74 years that were recruited between 2008 and 2011. Multi-stage complex survey design was utilized for sampling. Ineligibility criteria for the HCHS/SOL included: being on active military service, not currently living at home, planning to move from the area in the next 6 months, inability to complete the study in English or Spanish, and inability to attend the clinic examination. Details of sample design and cohort selection have been published previously. ,
The Echocardiographic Study of Latinos (ECHO-SOL) is an ancillary study of HCHS/SOL designed to provide the characteristics of abnormal cardiac structure and function and the association with acculturation and sociocultural factors among Hispanic/Latino adults. The study population of ECHO-SOL consists of 1,818 participants already enrolled in HCHS/SOL study across four US sites. Eligibility criteria for ECHO-SOL included: age 45 years or older, self-reported Hispanic/Latino background of Mexican, Puerto Rican, Cuban, Dominican, Central American, or South American, and 36 months or fewer from date of baseline visit. On average, ECHO-SOL had an ∼80% participation rate among eligible HCHS/SOL enrollees who were invited to participate. A detailed description of the design, rationale, and methods has been described previously. , The Institutional Review Board at each study site provided approval and oversight of all study materials and activities.
Consistent with prior literature, including meta-analysis on reference limits by the American Society of Echocardiography (ASE) and Hispanic/Latino population-based studies on echocardiographic reference values, our reference normal subgroup was selected using similar criteria. The ECHO-SOL reference healthy sample parameters included: systolic blood pressure (SBP) <140 mm Hg, diastolic blood pressure <90 mm Hg, no history of drug-treated HTN, no diagnosis of diabetes, fasting glucose <126 mg/dl, body mass index <30 kg/m 2, estimated glomerular filtration rate >60 ml/min/1.73 m 2 and no history of coronary heart disease.
Echocardiographic measurements
GLS measurements were performed by STE with vendor-independent TomTec Cardiac Performance Analysis software. Myocardial segments can be tracked along three orthogonal axes of the heart (radial, circumferential, and longitudinal) and provide a numerical value that represents the percent change in the shape of a myocardial segment from the end of diastole to peak contraction in a specific axis. GLS is the aggregate percent change of multiple segments along the longitudinal axis and is presented as a negative percentage. Apical 4-chamber and 2-chamber views of the LV were obtained to assess myocardial deformation. GLS was calculated by averaging strain values from 12 myocardial segments along the longitudinal axis during a cardiac cycle. More negative GLS values, larger absolute strain values denote better function. ,,
LVEF was derived from volumetric assessments and calculated following ASE guidelines by using the biplane method of discs (modified Simpson’s rule). The modified Simpson’s rule states that the volume of a 3-dimensional structure can be determined by dividing the structure into a sequence of 2-dimensional slices (or discs) and then summing the product of the cross-sectional area and thickness of each disc. End-diastolic (EDV) and end-systolic volumes (ESV) were measured using two-dimensional images optimized to avoid LV foreshortening or dropout and were used to ascertain LVEF. Stroke volume (SV) was calculated as the difference between EDV and ESV. LVEF was then derived using the formula: LVEF = (EDV– ESV)/EDV. Due to suboptimal image quality, LVEF could not be measured in approximately 4.9% of the ECHO-SOL cohort.
Statistical analysis
Survey methods that account for the complex survey design and sampling weights were applied to provide weighted frequencies of descriptive variables, and population estimates were used. Clinical and sociodemographic characteristics of the overall target population and the reference normal subgroup at the baseline visit are presented as means (standard errors) for continuous variables and as frequencies (percentages) for categorical variables. The distribution of the mean GLS was presented for the overall target population and further stratified by age, sex, and Hispanic/Latino background groups. We calculated overall and sex-specific summary statistics of GLS for the 25th, 90th, 95th, and 99th percentile values within the reference normal subgroup. The 95th percentile value of the reference normal population defined our lower limit of normal (LLN). The proportion of abnormal GLS was further stratified by sex, age groups (45 to 54, 55 to 64, >65), and Hispanic/Latino background groups were assessed with the Rao-Scott Chi-square test. We observed the frequencies and weighted proportions of abnormal LVEF and SV compared to the frequencies and proportions of abnormal GLS as defined by the reference healthy sample 95% LLN value. Normal LVEF was defined as 55%, and above. In addition, a sensitivity analysis was performed using the ASE cutoff of GLS–16% (which did not include Hispanic/Latinos in its derivation), to describe the proportion of abnormal GLS in comparison to our 95th percentile cutoff.
Means (standard errors) of GLS and frequencies (percentages) of the normal and abnormal for GLS were also examined by each major heart failure risk factor (HTN, obesity, and type 2 DM), and the cumulative number of risk factors. HTN was defined as a SBP ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or receiving antihypertensive medication. Obesity was defined as a BMI ≥ 30.0 kg/m 2. Type 2 DM was defined as a fasting plasma glucose ≥126 mg/dl, 2-hour postload plasma glucose ≥200 mg/dl, an HbA1c ≥6.5%, or use of antihyperglycemic medications. p Values were provided by linear regression for the comparison in mean values and the Rao-Scott Chi-square test for the comparison in proportion. Statistical significance was defined as p value <0.05. All reported values were weighted to adjust for sampling probability and nonresponse and accounted for the complex survey sampling design (clustering and stratification). All analyses were performed using PROC SURVEY with SAS version 9.3 (SAS Institute Inc., Cary, NC). Figures were created using GraphPad Prism version 8.0.0 for Windows.
Results
Our reference normal subpopulation consisted of 24.8% participants based on the criteria described. Baseline characteristics of the ECHO-SOL target population and the reference normal subpopulation ( Table 1 ) indicated that the two groups had fairly equal distribution by sex, but the reference normal subpopulation was slightly younger and had lower BMI than the overall target population. Clinical variables were similar in both groups, except for dyslipidemia. The reference normal subpopulation mean GLS was–18.2%, slightly lower (more negative value) than the overall target population mean GLS of–17.6%.
Table 1
Baseline demographic characteristics of the ECHO-SOL population and the reference normal subgroup
| Characteristics | Target population ( N = 1,818, 100%) | Reference normal subgroup ( N = 468, 24.8%) | |
|---|---|---|---|
| Age, years (mean [SE]) | 56.38 (0.37) | 53.23 (0.53) | |
| Male, % | 42.63% | 45.29% | |
| BMI, kg/m 2 (mean [SE]) | 30.11 (0.23) | 25.92 (0.15) | |
| BSA, m 2 (mean [SE]) | 1.84 (0.01) | 1.77 (0.01) | |
| Systolic BP, mm Hg (mean [SE]) | 136.19 (0.64) | 128.85 (1.14) | |
| Diastolic BP, mm Hg (mean [SE]) | 77.86 (0.42) | 75.58 (0.79) | |
| Fasting glucose, mg/dl (mean [SE]) | 106.32 (1.05) | 93.64 (0.42) | |
| HDL, mg/dL (mean [SE]) | 50.44 (0.41) | 53.31 (0.72) | |
| Total cholesterol, mg/dl (mean [SE]) | 208.61 (1.44) | 207.69 (2.26) | |
| Dyslipidemia, % | 40.95% | 31.02% | |
| Smoking, % | Current | 17.65% | 20.18% |
| Former | 25.69% | 25.51% | |
| Never | 56.66% | 54.31% | |
| Hispanic/Latino background group, % | Mexican | 20.41% | 30.48% |
| Puerto Rican | 17.13% | 10.54% | |
| Cuban | 31.62% | 31.03% | |
| South American | 6.17% | 7.24% | |
| Central American | 6.43% | 5.43% | |
| Dominican | 18.24% | 15.28% | |
All Ns are unweighted, and percentages (%) are weighted.
BMI = body mass index; BP = blood pressure; BSA = body surface area; HDL = high-density lipoprotein; SE = standard error.
The target population distribution of mean GLS was stratified by age, sex, and Hispanic/Latino background group ( Table 2 ). There were no significant differences in mean GLS across age groups (p = 0.09). When stratified by sex, females had a significantly lower mean GLS (more negative value) than males (–18.3% vs–16.5; p < 0.01). GLS significantly varied between Hispanic/Latino background groups (p < 0.01), with Hispanic/Latinos of Cuban background having the highest mean GLS (less negative value) and Hispanic/Latinos of South American background having the lowest mean GLS (more negative value). Table 3 lists the 25th, 90th, 95th, and 99th percentiles of GLS in the reference normal subpopulation. The sex-specific 95% percentile LLN for GLS established was lower (more negative value) for females (–14.8%) than for males (–13.0%).
Table 2
Distribution of global longitudinal strain in the target population stratified by age, sex, and Hispanic background group
| Overall target population GLS | Mean | Min | Max | N | SE | |
|---|---|---|---|---|---|---|
| –17.56 | –26.17 | –3.43 | 1,740.00 | 0.13 |
| GLS stratified by age | Mean | Min | Max | N | SE | p value |
|---|---|---|---|---|---|---|
| 45-54 years | –17.83 | –26.17 | –3.43 | 886 | 0.15 | 0.09 |
| 55-64 years | –17.51 | –25.70 | –5.84 | 647 | 0.15 | |
| 65+ years | –17.02 | –24.98 | –10.20 | 207 | 0.40 |
| GLS stratified by sex | Mean | Min | Max | N | SE | p value |
|---|---|---|---|---|---|---|
| Male | –16.49 | –24.96 | –3.43 | 594 | 0.16 | <0.01 |
| Female | –18.33 | –26.17 | –8.89 | 1,146 | 0.15 |
| GLS stratified by Hispanic/Latino background group | Mean | Min | Max | N | SE | p value |
|---|---|---|---|---|---|---|
| Dominican | –17.63 | –26.07 | –8.66 | 320 | 0.18 | <0.01 |
| Central American | –17.98 | –25.63 | –9.80 | 167 | 0.24 | |
| Cuban | –16.80 | –24.88 | –3.43 | 340 | 0.23 | |
| Mexican | –18.06 | –26.17 | –8.24 | 435 | 0.17 | |
| Puerto Rican | –17.80 | –23.68 | –5.84 | 330 | 0.41 | |
| South American | –18.44 | –25.27 | –10.49 | 144 | 0.27 |
All Ns are unweighted. Bolded values are statistically significant.
GLS = global longitudinal strain; SE = standard error.
Table 3
Percentiles * of global longitudinal strain for the reference normal subgroup and by sex-stratified subgroups
| Reference normal subgroup ( N = 468) | |||||
|---|---|---|---|---|---|
| Echocardiographic measures | Percentile | Value | SE | 95% CI | |
| GLS | Mean | –18.16 | 0.16 | –18.48 | –17.84 |
| 25th | –20.03 | 0.28 | –20.58 | –19.48 | |
| 90th | –14.73 | 0.32 | –15.35 | –14.11 | |
| 95th | –14.21 | 0.38 | –14.95 | –13.46 | |
| 99th | –11.81 | 1.16 | –14.09 | –9.53 | |
| Reference normal males subgroup ( N = 158) | |||||
|---|---|---|---|---|---|
| Echocardiographic measures | Percentile | Value | SE | 95% CI | |
| GLS | Mean | –17.09 | 0.25 | –17.58 | –16.61 |
| 25th | –18.57 | 0.35 | –19.27 | –17.88 | |
| 90th | –14.15 | 0.43 | –15.01 | –13.30 | |
| 95th | –12.99 | 0.65 | –14.28 | –11.71 | |
| 99th | –11.27 | . | . | . | |
| Reference normal females subgroup ( N = 310) | |||||
|---|---|---|---|---|---|
| Echocardiographic measures | Percentile | Value | SE | 95% CI | |
| GLS | Mean | –19.02 | 0.19 | –19.39 | –18.66 |
| 25th | –20.91 | 0.38 | –21.67 | –20.16 | |
| 90th | –15.48 | 0.43 | –16.34 | –14.63 | |
| 95th | –14.83 | 0.51 | –15.84 | –13.83 | |
| 99th | –14.35 | . | . | . | |
All Ns are unweighted.
CI = confidence intervals; GLS = global longitudinal strain; SE = standard error.
Based on the 95th percentile LLN in the overall normal reference group, abnormal GLS values were classified as greater than (less negative value)–14.2%. Applying the 95% percentile LLN values to the target ECHO-SOL population, we found 12.1% of the target population had abnormal GLS ( Figure 1 ), and the prevalence of abnormal GLS significantly varied by age, sex, and Hispanic/Latino background group. Abnormal GLS prevalence increased linearly with age, and more males had abnormal GLS than females (17.9% vs 7.8%, p < 0.01) ( Figure 1 ). Hispanic/Latino individuals of Central American background had the lowest prevalence of abnormal GLS, while Hispanic/Latinos of Cuban background had the highest (7.5% vs 18.9%, p < 0.01) ( Figure 1 ). In addition, our sensitivity analysis noted significant differences in abnormal GLS when using the ASE cutoff of–16% compared against our ECHO-SOL normal reference group cutoff resulting in a higher prevalence of abnormal GLS both overall (29.2% ASE vs 12.1% ECHO-SOL) and by group stratified analyses (age, sex, and Hispanic/Latino background) ( Supplementary Figure 1 ).
Weighted proportions of abnormal global longitudinal strain overall and across age, sex, and Hispanic/Latino background groups. Part (A) shows the weighted proportions of abnormal global longitudinal strain (GLS), defined using the 95% lower limit of normal (LLN) from the reference population (–14.2%), for the overall Hispanic/Latino population and across age and sex groups. Part (B) shows weighted proportions of abnormal GLS across disaggregated Hispanic/Latino background groups .
The proportion of normal and abnormal GLS values compared to the traditional echocardiographic measure of LVEF and SV were compared and shown in Figure 2 . More than half (56.4%) of individuals with abnormal GLS were classified as having normal LVEF. In addition, a smaller percentage of individuals with normal GLS were found to have abnormal LVEF (14%). Similarly, among abnormal GLS, only 52.8% of individuals had an abnormal SV. The ECHO-SOL target population was also stratified by the presence or absence of heart failure risk factors: HTN, obesity, and DM, as reported in Table 4 A. Individuals with HTN and DM had worse mean GLS (less negative value) compared to those without. The prevalence of HTN or DM was higher in individuals with abnormal GLS compared to those with normal GLS ( Table 4 B). The prevalence of obesity did not vary with normal versus abnormal GLS. Mean GLS significantly varied according to increasing heart failure risk factor burden (HTN, obesity, and/or DM) ( Table 4 C). As the number of comorbidities increased, mean GLS became worse (less negative). Individuals without any comorbidities had a mean GLS of–18.2%, compared to–16.3% in those with all three comorbidities (p < 0.01) ( Table 4 C). As the number of comorbidities increased, the percentage of participants with abnormal GLS also increased, with 25.6% of those with all three comorbidities having abnormal GLS.
Comparison of global longitudinal strain with left ventricular ejection fraction and stroke volume. Part (A) shows the weighted proportions of abnormal and normal global longitudinal strain (GLS) among participants with normal versus abnormal left ventricular ejection fraction (LVEF). Part (B) shows the weighted proportions of abnormal and normal GLS among participants with normal versus abnormal stroke volume (SV).
Table 4
Characterization of global longitudinal strain by risk factors
| (A)—Means for GLS according to each risk factor | |||||||
|---|---|---|---|---|---|---|---|
| Risk factors | GLS | ||||||
| Mean | SE | p value | |||||
| Hypertension (HTN) | No HTN | –18.04 | 0.14 | <0.01 | |||
| HTN | –16.96 | 0.22 | |||||
| Obesity | Nonobese | –17.58 | 0.14 | 0.83 | |||
| Obese | –17.53 | 0.21 | |||||
| Diabetes mellitus (DM) | Non-DM | –17.92 | 0.14 | <0.01 | |||
| DM | –16.62 | 0.21 | |||||
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