Prognostic power of conventional echocardiography in individuals without history of cardiovascular diseases: A systematic review and meta-analysis

Luciana Pereira Fernandes Ana Terra Fonseca Barreto Mansueto Gomes Neto Edmundo José Nassri Câmara André Rodrigues Durães Leonardo Roever Roque Aras-Júnior About the authors

Abstract

Echocardiographic abnormalities are associated with a higher incidence of adverse cardiovascular outcomes. This systematic review and meta-analysis aimed to evaluate whether echocardiographic abnormalities are predictors of cardiovascular events in individuals without previous cardiovascular diseases. The PubMed, Scopus, and SciELO databases were searched for longitudinal studies investigating the association between echocardiographic abnormalities and cardiovascular events among individuals without known cardiovascular diseases. Two independent reviewers analyzed data on the number of participants, age and sex, echocardiographic alterations, follow-up time, and cardiovascular outcomes. The meta-analysis estimated the risk ratio (RR) and 95% confidence interval (CI). Heterogeneity was assessed using I2 test. Twenty-two longitudinal studies met the eligibility criteria, comprising a total of 55,603 patients. Left ventricular hypertrophy (LVH) was associated with non-fatal cardiovascular events (RR 2.16; 95% CI 1.22-3.84), death from cardiovascular disease (RR 2.58; 95% CI 1.83- 3.64), and all-cause mortality (RR 2.02; 95% CI 1.34-3.04). Left ventricular diastolic dysfunction (LVDD) and left atrial dilation (LA) were associated with fatal and non-fatal cardiovascular events (RR 2.01; 95% CI 1.32-3.07) and (RR 1.78; 95% CI 1.16-2.73), respectively. Aortic root dilation was associated with non-fatal cardiovascular events (RR 1.25; 95% CI 1.09-1.43). In conclusion, LVH, LVDD, dilations of the LA, and of the aortic root were associated with an increased risk of adverse events in individuals without previous cardiovascular diseases. This study suggests that simple data obtained on conventional echocardiography can be an important predictor of cardiovascular outcomes in a low-risk population.

Echocardiography; Risk; Cardiovascular Disease; Cerebrovascular Accident; Mortality


INTRODUCTION

Cardiovascular diseases are the subject of extensive research because of their significant impact on morbidity and mortality worldwide (11. WHO. Cardiovascular diseases (CVDs). Available from: https://www.who.int/health-topics/cardiovascular-diseases/#tab=tab_1
https://www.who.int/health-topics/cardio...
). Echocardiography plays an important role in the initial investigation of cardiovascular risk and accounts for a high volume of cardiac imaging tests performed (22. Steeds RP, Garbi M, Cardim N, Kasprzak JD, Sade E, Nihoyannopoulos P, et al. EACVI appropriateness criteria for the use of transthoracic echocardiography in adults: a report of literature and current practice review. Eur Heart J Cardiovasc Imaging. 2017;18(11):1191-204. https://doi.org/10.1093/ehjci/jew333.
https://doi.org/10.1093/ehjci/jew333...
). Easy access and non-invasiveness have facilitated its widespread application, and has also increased the detection and diagnosis of several abnormalities in individuals without cardiovascular disease (33. Kerley RN, Thornton KP, Kelly RM, O’Flynn S. Appropriate use criteria for transthoracic echocardiography: Are they relevant to European centers? Echocardiography. 2018;35(1):17-23. https://doi.org/10.1111/echo.13730.
https://doi.org/10.1111/echo.13730...
).

In this context, studies have reported different results regarding the prognostic impact of echocardiographic abnormalities in asymptomatic individuals (44. Drazner MH, Rame JE, Marino EK, Gottdiener JS, Kitzman DW, Gardin JM, et al. Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the Cardiovascular Health Study. J Am Coll Cardiol. 2004;43(12):2207-15. https://doi.org/10.1016/j.jacc.2003.11.064.
https://doi.org/10.1016/j.jacc.2003.11.0...
,55. Zhou D, Huang Y, Fu M, Cai A, Tang S, Feng Y. Prognostic value of tissue Doppler E/e’ ratio in hypertension patients with preserved left ventricular ejection fraction. Clin Exp Hypertens. 2018;40(6):554-9. https://doi.org/10.1080/10641963.2017.1407332.
https://doi.org/10.1080/10641963.2017.14...
). To the best of our knowledge, no previous systematic review has analyzed echocardiographic abnormalities as predictors of cardiovascular risk. Accordingly, this systematic review and meta-analysis aimed to analyze published studies that investigated whether echocardiographic abnormalities are predictors of adverse cardiovascular outcomes in patients without previous cardiovascular diseases (e.g., myocardial infarction [MI], heart failure [HF], stroke, and atrial fibrillation [AF]).

METHODS

This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (66. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1-34. https://doi.org/10.1016/j.jclinepi.2009.06.006.
https://doi.org/10.1016/j.jclinepi.2009....
). The review protocol was registered in the PROSPERO database (CRD42018117704). Given the retrospective nature of the study (i.e., review and meta-analysis) and the use of anonymized data, the requirement for informed consent was waived.

Eligibility criteria

Longitudinal studies that addressed the association between echocardiographic abnormalities and adverse cardiovascular outcomes, including fatal and non-fatal MI, fatal and non-fatal stroke, HF, AF, and all-cause mortality in adults >18 years of age were included. Studies using other diagnostic imaging methods that analyzed other outcomes or whose participants had already experienced one of the outcomes were excluded.

Eligible studies were identified by searching the PubMed, Scopus, and Scientific Electronic Library Online (SciELO) databases up to December 2019 without language or publication status restrictions. Manual searches of relevant studies were also performed using Google Scholar. A standard protocol was used for the literature search and, whenever possible, using controlled vocabulary (i.e., MeSH term for PubMed). In the search strategy, three groups of keywords and their synonyms were used: study design, participants, and exposure. The optimally sensitive search strategy was used to identify studies in MEDLINE and PubMed. The full search strategy is presented in Table S1.

Data extraction

Two members of the study team (LPF and ATFB) independently evaluated a list of tittles and abstracts from each data source to identify potentially eligible studies for the systematic review. If at least one of the members considered a reference eligible, a full-text article was obtained for complete assessment.

Data regarding the following variables were extracted from each study: first author, year and country of publication, number of participants, age and sex, echocardiographic parameters analyzed, follow-up, and outcomes evaluated (Table 1). The extracted data were independently verified (i.e., double verification) by two members of the study team (LPF and ATFB). Disagreements were resolved by consensus or discussion with a third investigator (MGN).

Table 1
Characteristics of the included studies.

Study quality

The Newcastle-Ottawa Quality Assessment Scale (77. Wells G, Shea BJ, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Non-Randomized Studies in Meta-Analysis.Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
http://www.ohri.ca/programs/clinical_epi...
) for cohort studies was used to assess the quality of the included studies. The scale consisted of three categories: 1. Selection (sample representativeness, selection of the unexposed cohort, determination of exposure, and absence of selection bias); 2. Comparison between groups; 3. Outcome (analysis of outcomes, follow-up time, and adequacy of follow-up time). The total quality score was reported as the average score of the two researchers.

Statistical analysis

Risk ratio (RR) was calculated from the number of events and participants in each group (left ventricular diastolic dysfunction [LVDD] versus [vs.] control, left ventricular hypertrophy [LVH] vs. control, left atrial [LA] enlargement vs. control, and aortic root dilation vs. control) and used to compare dichotomous variables. Cardiovascular events (fatal and non-fatal), cardiovascular mortality, and all-cause mortality were analyzed. Pooled RR was calculated.

All p-values were two-tailed, with a statistical significance of 0.05, and confidence intervals (CIs) were calculated at the 95% level. The RR and 95% CIs were calculated. The heterogeneity of the treatment effect in the meta-analysis was examined using the I2 statistic. The I2 values >40% were considered to be indicative of high heterogeneity and, in this case, a random-effects model was chosen. Meta-analysis was conducted using Review Manager (version 5.3; Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration) (88. Collaboration TC. Available from: http://www.cochrane.org
http://www.cochrane.org...
). We only included the studies that presented the same type of exposure in the meta-analysis and analyzed the same outcomes.

RESULTS

Description of selected studies

The initial search retrieved 16,544 abstracts, of which 89 studies were considered potentially relevant and were included in the detailed analysis. Ultimately, 22 studies (99. Lind L, Sundström J. Change in left ventricular geometry over 10 years in the elderly and risk of incident cardiovascular disease. J Hypertens. 2019;37(2):325-30. https://doi.org/10.1097/HJH.0000000000001897.
https://doi.org/10.1097/HJH.000000000000...

10. Desai CS, Bartz TM, Gottdiener JS, Lloyd-Jones DM, Gardin JM. Usefulness of Left Ventricular Mass and Geometry for Determining 10-Year Prediction of Cardiovascular Disease in Adults Aged >65 Years (from the Cardiovascular Health Study). Am J Cardiol. 2016;118(5):684-90. https://doi.org/10.1016/j.amjcard.2016.06.016.
https://doi.org/10.1016/j.amjcard.2016.0...

11. Lieb W, Gona P, Larson MG, Aragam J, Zile MR, Cheng S, et al. The natural history of left ventricular geometry in the community: clinical correlates and prognostic significance of change in LV geometric pattern. JACC Cardiovasc Imaging. 2014;7(9):870-8. https://doi.org/10.1016/j.jcmg.2014.05.008.
https://doi.org/10.1016/j.jcmg.2014.05.0...

12. Armstrong AC, Jacobs DR Jr, Gidding SS, Colangelo LA, Gjesdal O, Lewis CE, et al. Framingham score and LV mass predict events in young adults: CARDIA study. Int J Cardiol. 2014;172(2):350-5. https://doi.org/10.1016/j.ijcard.2014.01.003.
https://doi.org/10.1016/j.ijcard.2014.01...

13. Lai CL, Chien KL, Hsu HC, Su TC, Chen MF, Lee YT. Left ventricular mass and risk of cardiovascular events and all-cause death among ethnic Chinese-the Chin-Shan Community Cardiovascular Cohort study. Int J Cardiol. 2011;149(3):347-52. https://doi.org/10.1016/j.ijcard.2010.02.015.
https://doi.org/10.1016/j.ijcard.2010.02...

14. Krumholz HM, Larson M, Levy D. Prognosis of left ventricular geometric patterns in the Framingham Heart Study. J Am Coll Cardiol. 1995;25(4):879-84. https://doi.org/10.1016/0735-1097(94)00473-4.
https://doi.org/10.1016/0735-1097(94)004...

15. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;322(22):1561-6. https://doi.org/10.1056/NEJM199005313222203.
https://doi.org/10.1056/NEJM199005313222...

16. Nayor M, Cooper LL, Enserro DM, Xanthakis V, Larson MG, Benjamin EJ, et al. Left Ventricular Diastolic Dysfunction in the Community: Impact of Diagnostic Criteria on the Burden, Correlates, and Prognosis. J Am Heart Assoc. 2018;7(11):e008291. https://doi.org/10.1161/JAHA.117.008291
https://doi.org/10.1161/JAHA.117.008291...

17. AlJaroudi WA, Alraies MC, Halley C, Menon V, Rodriguez LL, Grimm RA, et al. Incremental prognostic value of diastolic dysfunction in low risk patients undergoing echocardiography: beyond Framingham score. Int J Cardiovasc Imaging. 2013;29(7):1441-50. https://doi.org/10.1007/s10554-013-0246-2.
https://doi.org/10.1007/s10554-013-0246-...

18. Desai CS, Colangelo LA, Liu K, Jacobs DR Jr, Cook NL, Lloyd-Jones DM, et al. Prevalence, prospective risk markers, and prognosis associated with the presence of left ventricular diastolic dysfunction in young adults: the coronary artery risk development in young adults study. Am J Epidemiol. 2013;177(1):20-32. https://doi.org/10.1093/aje/kws224.
https://doi.org/10.1093/aje/kws224...

19. Kardys I, Deckers JW, Stricker BH, Vletter WB, Hofman A, Witteman JC. Echocardiographic parameters and all-cause mortality: the Rotterdam Study. Int J Cardiol. 2009;133(2):198-204. https://doi.org/10.1016/j.ijcard.2007.12.031.
https://doi.org/10.1016/j.ijcard.2007.12...

20. Bombelli M, Facchetti R, Cuspidi C, Villa P, Dozio D, Brambilla G, et al. Prognostic significance of left atrial enlargement in a general population results of the PAMELA study. Hypertension. 2014;64(6):1205-11. https://doi.org/10.1161/HYPERTENSIONAHA.114.03975.
https://doi.org/10.1161/HYPERTENSIONAHA....

21. Armstrong AC, Liu K, Lewis CE, Sidney S, Colangelo LA, Kishi S, et al. Left atrial dimension and traditional cardiovascular risk factors predict 20-year clinical cardiovascular events in young healthy adults: the CARDIA study. Eur Hear J Cardiovasc Imaging. 2014;15(8):893-9. https://doi.org/10.1093/ehjci/jeu018.
https://doi.org/10.1093/ehjci/jeu018...

22. Kizer JR, Bella JN, Palmieri V, Liu JE, Best LG, Lee ET, et al. Left atrial diameter as an independent predictor of first clinical cardiovascular events in middle-aged and elderly adults: the Strong Heart Study (SHS). Am Heart J. 2006;151(2):412-8. https://doi.org/10.1016/j.ahj.2005.04.031.
https://doi.org/10.1016/j.ahj.2005.04.03...

23. Laukkanen JA, Kurl S, Eränen J, Huttunen M, Salonen JT. Left atrium size and the risk of cardiovascular death in middle-aged men. Arch Intern Med. 2005;165(15):1788-93. https://doi.org/10.1001/archinte.165.15.1788.
https://doi.org/10.1001/archinte.165.15....

24. Tsang TS, Barnes ME, Gersh BJ, Takemoto Y, Rosales AG, Bailey KR, et al. Prediction of risk for first age-related cardiovascular events in an elderly population: the incremental value of echocardiography. J Am Coll Cardiol. 2003;42(7):1199-205. https://doi.org/10.1016/S0735-1097(03)00943-4.
https://doi.org/10.1016/S0735-1097(03)00...

25. Cuspidi C, Facchetti R, Bombelli M, Re A, Cairoa M, Sala C, et al. Aortic root diameter and risk of cardiovascular events in a general population: data from the PAMELA study. J Hypertens. 2014;32(9):1879-87. https://doi.org/10.1097/HJH.0000000000000264.
https://doi.org/10.1097/HJH.000000000000...

26. Lai CL, Chien KL, Hsu HC, Su TC, Chen MF, Lee YT. Aortic root dimension as an independent predictor for all-cause death in adults <65 years of age (from the Chin-Shan Community Cardiovascular Cohort Study). Echocardiography. 2010;27(5):487-95. https://doi.org/10.1111/j.1540-8175.2009.01072.x.
https://doi.org/10.1111/j.1540-8175.2009...

27. Gardin JM, Arnold AM, Polak J, Jackson S, Smith V, Gottdiener J. Usefulness of aortic root dimension in persons > or = 65 years of age in predicting heart failure, stroke, cardiovascular mortality, all-cause mortality and acute myocardial infarction (from the Cardiovascular Health Study). Am J Cardiol. 2006;97(2):270-5. https://doi.org/10.1016/j.amjcard.2005.08.039.
https://doi.org/10.1016/j.amjcard.2005.0...

28. Völzke H, Haring R, Lorbeer R, Wallaschofski H, Reffelmann T, Empen K, et al. Heart valve sclerosis predicts all-cause and cardiovascular mortality. Atherosclerosis. 2010;209(2):606-10. https://doi.org/10.1016/j.atherosclerosis.2009.10.030.
https://doi.org/10.1016/j.atherosclerosi...

29. Kizer JR, Wiebers DO, Whisnant JP, Galloway JM, Welty TK, Lee ET, et al. Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study. Stroke. 2005;36(12):2533-7. https://doi.org/10.1161/01.STR.0000190005.09442.ad.
https://doi.org/10.1161/01.STR.000019000...
-3030. Gardin JM, McClelland R, Kitzman D, Lima JA, Bommer W, Klopfenstein HS, et al. M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study). Am J Cardiol. 2001;87(9):1051-7. https://doi.org/10.1016/S0002-9149(01)01460-6.
https://doi.org/10.1016/S0002-9149(01)01...
) met the eligibility criteria, and nine were included in the meta-analysis (1313. Lai CL, Chien KL, Hsu HC, Su TC, Chen MF, Lee YT. Left ventricular mass and risk of cardiovascular events and all-cause death among ethnic Chinese-the Chin-Shan Community Cardiovascular Cohort study. Int J Cardiol. 2011;149(3):347-52. https://doi.org/10.1016/j.ijcard.2010.02.015.
https://doi.org/10.1016/j.ijcard.2010.02...

14. Krumholz HM, Larson M, Levy D. Prognosis of left ventricular geometric patterns in the Framingham Heart Study. J Am Coll Cardiol. 1995;25(4):879-84. https://doi.org/10.1016/0735-1097(94)00473-4.
https://doi.org/10.1016/0735-1097(94)004...

15. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;322(22):1561-6. https://doi.org/10.1056/NEJM199005313222203.
https://doi.org/10.1056/NEJM199005313222...
-1616. Nayor M, Cooper LL, Enserro DM, Xanthakis V, Larson MG, Benjamin EJ, et al. Left Ventricular Diastolic Dysfunction in the Community: Impact of Diagnostic Criteria on the Burden, Correlates, and Prognosis. J Am Heart Assoc. 2018;7(11):e008291. https://doi.org/10.1161/JAHA.117.008291
https://doi.org/10.1161/JAHA.117.008291...
,1818. Desai CS, Colangelo LA, Liu K, Jacobs DR Jr, Cook NL, Lloyd-Jones DM, et al. Prevalence, prospective risk markers, and prognosis associated with the presence of left ventricular diastolic dysfunction in young adults: the coronary artery risk development in young adults study. Am J Epidemiol. 2013;177(1):20-32. https://doi.org/10.1093/aje/kws224.
https://doi.org/10.1093/aje/kws224...
,2020. Bombelli M, Facchetti R, Cuspidi C, Villa P, Dozio D, Brambilla G, et al. Prognostic significance of left atrial enlargement in a general population results of the PAMELA study. Hypertension. 2014;64(6):1205-11. https://doi.org/10.1161/HYPERTENSIONAHA.114.03975.
https://doi.org/10.1161/HYPERTENSIONAHA....
,2626. Lai CL, Chien KL, Hsu HC, Su TC, Chen MF, Lee YT. Aortic root dimension as an independent predictor for all-cause death in adults <65 years of age (from the Chin-Shan Community Cardiovascular Cohort Study). Echocardiography. 2010;27(5):487-95. https://doi.org/10.1111/j.1540-8175.2009.01072.x.
https://doi.org/10.1111/j.1540-8175.2009...
,2727. Gardin JM, Arnold AM, Polak J, Jackson S, Smith V, Gottdiener J. Usefulness of aortic root dimension in persons > or = 65 years of age in predicting heart failure, stroke, cardiovascular mortality, all-cause mortality and acute myocardial infarction (from the Cardiovascular Health Study). Am J Cardiol. 2006;97(2):270-5. https://doi.org/10.1016/j.amjcard.2005.08.039.
https://doi.org/10.1016/j.amjcard.2005.0...
,2929. Kizer JR, Wiebers DO, Whisnant JP, Galloway JM, Welty TK, Lee ET, et al. Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study. Stroke. 2005;36(12):2533-7. https://doi.org/10.1161/01.STR.0000190005.09442.ad.
https://doi.org/10.1161/01.STR.000019000...
). The PRISMA flow diagram of the studies in this review is presented in Figure 1. The results of the assessment of the Newcastle-Ottawa Quality Assessment Scale are presented individually in Table S2.

Figure 1
PRISMA flow diagram showing study identification, selection, eligibility, and inclusion.

Study characteristics

The studies were conducted in seven countries between 1990 and 2019, including a total of 55,603 patients in the systematic review and 24,639 patients in the meta-analysis. There was a predominance of females (55.6%), with an average age of 55.4 years. Most studies included adults >40 years of age, six elderly individuals, three healthy young individuals, and two evaluated Native Americans. North American population studies (14 studies) predominated, followed by six European and two Chinese studies. The mean follow-up period was 10.4 years. All studies, except for two (1717. AlJaroudi WA, Alraies MC, Halley C, Menon V, Rodriguez LL, Grimm RA, et al. Incremental prognostic value of diastolic dysfunction in low risk patients undergoing echocardiography: beyond Framingham score. Int J Cardiovasc Imaging. 2013;29(7):1441-50. https://doi.org/10.1007/s10554-013-0246-2.
https://doi.org/10.1007/s10554-013-0246-...
,2424. Tsang TS, Barnes ME, Gersh BJ, Takemoto Y, Rosales AG, Bailey KR, et al. Prediction of risk for first age-related cardiovascular events in an elderly population: the incremental value of echocardiography. J Am Coll Cardiol. 2003;42(7):1199-205. https://doi.org/10.1016/S0735-1097(03)00943-4.
https://doi.org/10.1016/S0735-1097(03)00...
), were prospective cohorts, and all were adjusted for possible confounding variables (sociodemographic, clinical, or echocardiographic) using multivariate analysis. The characteristics of the included studies are summarized in Table 1.

The effects of echocardiographic abnormalities on clinical results

Four studies (99. Lind L, Sundström J. Change in left ventricular geometry over 10 years in the elderly and risk of incident cardiovascular disease. J Hypertens. 2019;37(2):325-30. https://doi.org/10.1097/HJH.0000000000001897.
https://doi.org/10.1097/HJH.000000000000...

10. Desai CS, Bartz TM, Gottdiener JS, Lloyd-Jones DM, Gardin JM. Usefulness of Left Ventricular Mass and Geometry for Determining 10-Year Prediction of Cardiovascular Disease in Adults Aged >65 Years (from the Cardiovascular Health Study). Am J Cardiol. 2016;118(5):684-90. https://doi.org/10.1016/j.amjcard.2016.06.016.
https://doi.org/10.1016/j.amjcard.2016.0...
-1111. Lieb W, Gona P, Larson MG, Aragam J, Zile MR, Cheng S, et al. The natural history of left ventricular geometry in the community: clinical correlates and prognostic significance of change in LV geometric pattern. JACC Cardiovasc Imaging. 2014;7(9):870-8. https://doi.org/10.1016/j.jcmg.2014.05.008.
https://doi.org/10.1016/j.jcmg.2014.05.0...
,1414. Krumholz HM, Larson M, Levy D. Prognosis of left ventricular geometric patterns in the Framingham Heart Study. J Am Coll Cardiol. 1995;25(4):879-84. https://doi.org/10.1016/0735-1097(94)00473-4.
https://doi.org/10.1016/0735-1097(94)004...
) that analyzed the association between left ventricular (LV) geometry and the incidence of adverse cardiovascular outcomes reported that individuals with concentric or eccentric hypertrophy had higher cardiovascular risk.

Regarding the association between LV mass and cardiovascular outcomes, Armstrong et al. (1212. Armstrong AC, Jacobs DR Jr, Gidding SS, Colangelo LA, Gjesdal O, Lewis CE, et al. Framingham score and LV mass predict events in young adults: CARDIA study. Int J Cardiol. 2014;172(2):350-5. https://doi.org/10.1016/j.ijcard.2014.01.003.
https://doi.org/10.1016/j.ijcard.2014.01...
) found that adding LV mass to the Framingham score modestly increased discrimination. Lai et al. (1313. Lai CL, Chien KL, Hsu HC, Su TC, Chen MF, Lee YT. Left ventricular mass and risk of cardiovascular events and all-cause death among ethnic Chinese-the Chin-Shan Community Cardiovascular Cohort study. Int J Cardiol. 2011;149(3):347-52. https://doi.org/10.1016/j.ijcard.2010.02.015.
https://doi.org/10.1016/j.ijcard.2010.02...
) found a significant association among Chinese individuals. Levi et al. (1515. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;322(22):1561-6. https://doi.org/10.1056/NEJM199005313222203.
https://doi.org/10.1056/NEJM199005313222...
) observed an association between an increase in LV mass and a higher risk of adverse cardiovascular outcomes in the Framingham cohort.

A meta-analysis of the association between LVH and non-fatal cardiovascular events, fatal cardiovascular events, and all-cause mortality is shown in Figures 2.1, 2.2, and 2.3. The RR of the associations of LVH with non-fatal cardiovascular events, fatal cardiovascular events and with mortality from all causes were: 2.16 (95% CI 1.22-3.84), 2.58 (95% CI 1.83-3.64), and 2.02 (95% CI 1.34-3.04), respectively, indicating a significantly increased risk for these events in the LVH group versus the non-LVH group (p<0.01).

Figure 2.1
The Risk Ratio and 95% confidence interval (CI) in the cardiovascular events (non-fatal), for Left Ventricular Hypertrophy group versus the Control group.
Figure 2.2
The Risk Ratio and 95% confidence interval (CI) in the cardiovascular mortality, for Left Ventricular Hypertrophy group versus the Control group.
Figure 2.3
The Risk Ratio and 95% confidence interval (CI) in the all-cause mortality, for Left Ventricular Hypertrophy group versus the Control group.

Meta-analysis of the association between LVDD and cardiovascular events (fatal and non-fatal), LA enlargement and cardiovascular events (fatal and non-fatal), aortic root dilation and all-cause mortality, aortic root dilation, and non-fatal cardiovascular events are shown in Figures 3.1, 3.2, 3.3, and 3.8, respectively.

Figure 3.1
The Risk Ratio and 95% confidence interval (CI) in the cardiovascular events (fatal and non-fatal), for Left Ventricular Diastolic Dysfunction group versus the Control group.
Figure 3.2
The Risk Ratio and 95% confidence interval (CI) in the cardiovascular events (fatal and non-fatal), for Left Atrial enlargement group versus the Control group.
Figure 3.3
The Risk Ratio and 95% confidence interval (CI) in the all-cause mortality, for aortic root dilation group versus the Control group.
Figure 3.4
The Risk Ratio and 95% confidence interval (CI) in the cardiovascular events (non-fatal), for aortic root dilation group versus the Control group.

Among the studies that evaluated LVDD (1616. Nayor M, Cooper LL, Enserro DM, Xanthakis V, Larson MG, Benjamin EJ, et al. Left Ventricular Diastolic Dysfunction in the Community: Impact of Diagnostic Criteria on the Burden, Correlates, and Prognosis. J Am Heart Assoc. 2018;7(11):e008291. https://doi.org/10.1161/JAHA.117.008291
https://doi.org/10.1161/JAHA.117.008291...

17. AlJaroudi WA, Alraies MC, Halley C, Menon V, Rodriguez LL, Grimm RA, et al. Incremental prognostic value of diastolic dysfunction in low risk patients undergoing echocardiography: beyond Framingham score. Int J Cardiovasc Imaging. 2013;29(7):1441-50. https://doi.org/10.1007/s10554-013-0246-2.
https://doi.org/10.1007/s10554-013-0246-...

18. Desai CS, Colangelo LA, Liu K, Jacobs DR Jr, Cook NL, Lloyd-Jones DM, et al. Prevalence, prospective risk markers, and prognosis associated with the presence of left ventricular diastolic dysfunction in young adults: the coronary artery risk development in young adults study. Am J Epidemiol. 2013;177(1):20-32. https://doi.org/10.1093/aje/kws224.
https://doi.org/10.1093/aje/kws224...
-1919. Kardys I, Deckers JW, Stricker BH, Vletter WB, Hofman A, Witteman JC. Echocardiographic parameters and all-cause mortality: the Rotterdam Study. Int J Cardiol. 2009;133(2):198-204. https://doi.org/10.1016/j.ijcard.2007.12.031.
https://doi.org/10.1016/j.ijcard.2007.12...
), Nayor et al. (1616. Nayor M, Cooper LL, Enserro DM, Xanthakis V, Larson MG, Benjamin EJ, et al. Left Ventricular Diastolic Dysfunction in the Community: Impact of Diagnostic Criteria on the Burden, Correlates, and Prognosis. J Am Heart Assoc. 2018;7(11):e008291. https://doi.org/10.1161/JAHA.117.008291
https://doi.org/10.1161/JAHA.117.008291...
) assessed the impact of age- and sex-specific criteria on the diagnosis of LVDD and found that, based on these criteria, LVDD assessment was less age-dependent and more associated with incidental cardiovascular disease. Aljaroudi et al. (1717. AlJaroudi WA, Alraies MC, Halley C, Menon V, Rodriguez LL, Grimm RA, et al. Incremental prognostic value of diastolic dysfunction in low risk patients undergoing echocardiography: beyond Framingham score. Int J Cardiovasc Imaging. 2013;29(7):1441-50. https://doi.org/10.1007/s10554-013-0246-2.
https://doi.org/10.1007/s10554-013-0246-...
) evaluated the incremental prognostic value of LVDD in the Framingham risk score and observed that, even after adjusting for age, sex, and race, LVDD remained an independent predictor of death from all causes. Desai et al. (1818. Desai CS, Colangelo LA, Liu K, Jacobs DR Jr, Cook NL, Lloyd-Jones DM, et al. Prevalence, prospective risk markers, and prognosis associated with the presence of left ventricular diastolic dysfunction in young adults: the coronary artery risk development in young adults study. Am J Epidemiol. 2013;177(1):20-32. https://doi.org/10.1093/aje/kws224.
https://doi.org/10.1093/aje/kws224...
) evaluated the prevalence and prognosis of LVDD in young adults and found that LVDD was associated with high cardiovascular morbidity and mortality. Finally, in a cohort of the Rotterdam Study, Kardys et al. (1919. Kardys I, Deckers JW, Stricker BH, Vletter WB, Hofman A, Witteman JC. Echocardiographic parameters and all-cause mortality: the Rotterdam Study. Int J Cardiol. 2009;133(2):198-204. https://doi.org/10.1016/j.ijcard.2007.12.031.
https://doi.org/10.1016/j.ijcard.2007.12...
) found that asymptomatic individuals with LVDD had a higher risk of death from all causes.

In this study, we found a significant increase in the risk of fatal and non-fatal cardiovascular events in the LVDD group compared to the control group, with an RR of 2.01 (95% CI 1.32-3.07), as shown in Figure 3.1.

Five studies assessed the association between LA dilation and the risk of cardiovascular events (2020. Bombelli M, Facchetti R, Cuspidi C, Villa P, Dozio D, Brambilla G, et al. Prognostic significance of left atrial enlargement in a general population results of the PAMELA study. Hypertension. 2014;64(6):1205-11. https://doi.org/10.1161/HYPERTENSIONAHA.114.03975.
https://doi.org/10.1161/HYPERTENSIONAHA....

21. Armstrong AC, Liu K, Lewis CE, Sidney S, Colangelo LA, Kishi S, et al. Left atrial dimension and traditional cardiovascular risk factors predict 20-year clinical cardiovascular events in young healthy adults: the CARDIA study. Eur Hear J Cardiovasc Imaging. 2014;15(8):893-9. https://doi.org/10.1093/ehjci/jeu018.
https://doi.org/10.1093/ehjci/jeu018...

22. Kizer JR, Bella JN, Palmieri V, Liu JE, Best LG, Lee ET, et al. Left atrial diameter as an independent predictor of first clinical cardiovascular events in middle-aged and elderly adults: the Strong Heart Study (SHS). Am Heart J. 2006;151(2):412-8. https://doi.org/10.1016/j.ahj.2005.04.031.
https://doi.org/10.1016/j.ahj.2005.04.03...

23. Laukkanen JA, Kurl S, Eränen J, Huttunen M, Salonen JT. Left atrium size and the risk of cardiovascular death in middle-aged men. Arch Intern Med. 2005;165(15):1788-93. https://doi.org/10.1001/archinte.165.15.1788.
https://doi.org/10.1001/archinte.165.15....
-2424. Tsang TS, Barnes ME, Gersh BJ, Takemoto Y, Rosales AG, Bailey KR, et al. Prediction of risk for first age-related cardiovascular events in an elderly population: the incremental value of echocardiography. J Am Coll Cardiol. 2003;42(7):1199-205. https://doi.org/10.1016/S0735-1097(03)00943-4.
https://doi.org/10.1016/S0735-1097(03)00...
). Bombelli et al. (2020. Bombelli M, Facchetti R, Cuspidi C, Villa P, Dozio D, Brambilla G, et al. Prognostic significance of left atrial enlargement in a general population results of the PAMELA study. Hypertension. 2014;64(6):1205-11. https://doi.org/10.1161/HYPERTENSIONAHA.114.03975.
https://doi.org/10.1161/HYPERTENSIONAHA....
) found that LA dilation was an independent factor for the incidence of cardiovascular events in the general population. In contrast, Armstrong et al. (2121. Armstrong AC, Liu K, Lewis CE, Sidney S, Colangelo LA, Kishi S, et al. Left atrial dimension and traditional cardiovascular risk factors predict 20-year clinical cardiovascular events in young healthy adults: the CARDIA study. Eur Hear J Cardiovasc Imaging. 2014;15(8):893-9. https://doi.org/10.1093/ehjci/jeu018.
https://doi.org/10.1093/ehjci/jeu018...
) did not observe any increase in cardiovascular risk prediction when LA dimensions were added to the Framingham risk score. Kizer et al. (2222. Kizer JR, Bella JN, Palmieri V, Liu JE, Best LG, Lee ET, et al. Left atrial diameter as an independent predictor of first clinical cardiovascular events in middle-aged and elderly adults: the Strong Heart Study (SHS). Am Heart J. 2006;151(2):412-8. https://doi.org/10.1016/j.ahj.2005.04.031.
https://doi.org/10.1016/j.ahj.2005.04.03...
) found that LA dilation was an independent predictor of first cardiovascular events in a population of middle-aged and elderly adults. Laukkanen et al. (2323. Laukkanen JA, Kurl S, Eränen J, Huttunen M, Salonen JT. Left atrium size and the risk of cardiovascular death in middle-aged men. Arch Intern Med. 2005;165(15):1788-93. https://doi.org/10.1001/archinte.165.15.1788.
https://doi.org/10.1001/archinte.165.15....
) did not find a statistically significant association between LA dilation and cardiovascular mortality after adjusting for LV mass in a cohort of middle-aged men. Finally, Tsang et al. (2424. Tsang TS, Barnes ME, Gersh BJ, Takemoto Y, Rosales AG, Bailey KR, et al. Prediction of risk for first age-related cardiovascular events in an elderly population: the incremental value of echocardiography. J Am Coll Cardiol. 2003;42(7):1199-205. https://doi.org/10.1016/S0735-1097(03)00943-4.
https://doi.org/10.1016/S0735-1097(03)00...
) found that LA dilation was a robust predictor of first cardiovascular events in the elderly population.

As seen in Figure 3.2, we observed in this study a significantly increased risk of cardiovascular events in the group with increased LA compared to the control group with RR of 1.78 (95% CI 1.16-2.73).

Three studies estimated the association between aortic root dilation and cardiovascular risk (2525. Cuspidi C, Facchetti R, Bombelli M, Re A, Cairoa M, Sala C, et al. Aortic root diameter and risk of cardiovascular events in a general population: data from the PAMELA study. J Hypertens. 2014;32(9):1879-87. https://doi.org/10.1097/HJH.0000000000000264.
https://doi.org/10.1097/HJH.000000000000...

26. Lai CL, Chien KL, Hsu HC, Su TC, Chen MF, Lee YT. Aortic root dimension as an independent predictor for all-cause death in adults <65 years of age (from the Chin-Shan Community Cardiovascular Cohort Study). Echocardiography. 2010;27(5):487-95. https://doi.org/10.1111/j.1540-8175.2009.01072.x.
https://doi.org/10.1111/j.1540-8175.2009...
-2727. Gardin JM, Arnold AM, Polak J, Jackson S, Smith V, Gottdiener J. Usefulness of aortic root dimension in persons > or = 65 years of age in predicting heart failure, stroke, cardiovascular mortality, all-cause mortality and acute myocardial infarction (from the Cardiovascular Health Study). Am J Cardiol. 2006;97(2):270-5. https://doi.org/10.1016/j.amjcard.2005.08.039.
https://doi.org/10.1016/j.amjcard.2005.0...
). Cuspidi et al. (2525. Cuspidi C, Facchetti R, Bombelli M, Re A, Cairoa M, Sala C, et al. Aortic root diameter and risk of cardiovascular events in a general population: data from the PAMELA study. J Hypertens. 2014;32(9):1879-87. https://doi.org/10.1097/HJH.0000000000000264.
https://doi.org/10.1097/HJH.000000000000...
) found a significant association between height-indexed aortic root dilation and cardiovascular risk in middle-aged individuals. Lai et al. (2626. Lai CL, Chien KL, Hsu HC, Su TC, Chen MF, Lee YT. Aortic root dimension as an independent predictor for all-cause death in adults <65 years of age (from the Chin-Shan Community Cardiovascular Cohort Study). Echocardiography. 2010;27(5):487-95. https://doi.org/10.1111/j.1540-8175.2009.01072.x.
https://doi.org/10.1111/j.1540-8175.2009...
) observed an increase in the incidence of cardiovascular events in a Chinese population aged <65 years with aortic root dilation. Finally, Gardin et al. (2727. Gardin JM, Arnold AM, Polak J, Jackson S, Smith V, Gottdiener J. Usefulness of aortic root dimension in persons > or = 65 years of age in predicting heart failure, stroke, cardiovascular mortality, all-cause mortality and acute myocardial infarction (from the Cardiovascular Health Study). Am J Cardiol. 2006;97(2):270-5. https://doi.org/10.1016/j.amjcard.2005.08.039.
https://doi.org/10.1016/j.amjcard.2005.0...
) observed that elderly individuals with aortic root dilation demonstrated an increased risk of cardiovascular events, except for acute MI.

In this study, we found no association between dilation of the aortic root and mortality from all causes, with RR=1.64; 95% CI 0.92-2.94 (Figure 3.3), but we found in relation to non-fatal cardiovascular events, with RR=1.25; 95% CI 1.09-1.43 (Figure 3.4).

Three studies analyzed the association between aortic valve (AV) sclerosis and mitral annular calcification (MAC) and the risk of cardiovascular events in healthy individuals (2828. Völzke H, Haring R, Lorbeer R, Wallaschofski H, Reffelmann T, Empen K, et al. Heart valve sclerosis predicts all-cause and cardiovascular mortality. Atherosclerosis. 2010;209(2):606-10. https://doi.org/10.1016/j.atherosclerosis.2009.10.030.
https://doi.org/10.1016/j.atherosclerosi...

29. Kizer JR, Wiebers DO, Whisnant JP, Galloway JM, Welty TK, Lee ET, et al. Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study. Stroke. 2005;36(12):2533-7. https://doi.org/10.1161/01.STR.0000190005.09442.ad.
https://doi.org/10.1161/01.STR.000019000...
-3030. Gardin JM, McClelland R, Kitzman D, Lima JA, Bommer W, Klopfenstein HS, et al. M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study). Am J Cardiol. 2001;87(9):1051-7. https://doi.org/10.1016/S0002-9149(01)01460-6.
https://doi.org/10.1016/S0002-9149(01)01...
). Völzke et al. (2828. Völzke H, Haring R, Lorbeer R, Wallaschofski H, Reffelmann T, Empen K, et al. Heart valve sclerosis predicts all-cause and cardiovascular mortality. Atherosclerosis. 2010;209(2):606-10. https://doi.org/10.1016/j.atherosclerosis.2009.10.030.
https://doi.org/10.1016/j.atherosclerosi...
) found that both AV sclerosis and MAC increased the risk of all-cause and cardiovascular mortality. Kizer et al. (2929. Kizer JR, Wiebers DO, Whisnant JP, Galloway JM, Welty TK, Lee ET, et al. Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study. Stroke. 2005;36(12):2533-7. https://doi.org/10.1161/01.STR.0000190005.09442.ad.
https://doi.org/10.1161/01.STR.000019000...
) reported an increased risk of stroke among Native Americans with MAC, but not among those with AV sclerosis. Finally, Gardin et al. (3030. Gardin JM, McClelland R, Kitzman D, Lima JA, Bommer W, Klopfenstein HS, et al. M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study). Am J Cardiol. 2001;87(9):1051-7. https://doi.org/10.1016/S0002-9149(01)01460-6.
https://doi.org/10.1016/S0002-9149(01)01...
) concluded that MAC was a predictor of incidental coronary heart disease in an elderly cohort. However, it was not possible to perform meta-analyses in these studies.

DISCUSSION

Echocardiography is a non-invasive and easy-to-perform test that can detect many changes in cardiac structure and function frequently associated with cardiovascular prognosis in different situations, and it should also be used for this purpose.

To the best of our knowledge, this is the first meta-analysis to specifically investigate the role of some typical parameters of a conventional echocardiogram in a long-term prognosis in individuals without known previous cardiovascular events, including a total of 55,603 patients in the systematic review and 24,639 in the meta-analysis.

LVH, LVDD, LA enlargement, and aortic root dilation were associated with an incremental risk of adverse cardiovascular outcomes in this population, including fatal and non-fatal events, as well as all-cause mortality for LVH.

LVH and geometric patterns have long been recognized as predictors of increased cardiovascular risk. A meta-analysis published in 2001 reported that patients with LVH had twice the risk of cardiovascular events and death, regardless of other risk factors (3131. Vakili BA, Okin PM, Devereux RB. Prognostic implications of left ventricular hypertrophy. Am Heart J. 2001;141(3):334-41. https://doi.org/10.1067/mhj.2001.113218.
https://doi.org/10.1067/mhj.2001.113218...
). Our findings are consistent with this finding, even in an asymptomatic population.

An important finding of this meta-analysis is the significant association of any grade of diastolic dysfunction with fatal and non-fatal cardiovascular events in individuals without known previous cardiovascular diseases. This reinforces the view that the finding of LVDD should not be directed towards the diagnosis of HF, but should also be valued as an early marker of cardiovascular prognosis.

LVDD is typically seen in patients with hypertension but can also occur in a variety of other clinical disorders and has a particularly high prevalence in the elderly population (3232. Aziz F, Tk LA, Enweluzo C, Dutta S, Zaeem M. Diastolic heart failure: a concise review. J Clin Med Res. 2013;5(5):327-34. https://doi.org/10.4021/jocmr1532w.
https://doi.org/10.4021/jocmr1532w...
). The association between LVDD and fatal and non-fatal cardiovascular events that we found was also seen by Seko et al. (3333. Seko Y, Kato T, Shiba M, Morita Y, Yamaji Y, Haruna Y, et al. Association of the low e′ and high E/e′ with long-term outcomes in patients with normal ejection fraction: a hospital population-based observational cohort study. BMJ Open. 2019;9(11):e032663. https://doi.org/10.1136/bmjopen-2019-032663
https://doi.org/10.1136/bmjopen-2019-032...
), who, found a statistically significant association between LVDD and all-cause mortality. Other community studies involving the general population also demonstrated a significant predictive value of LVDD for cardiovascular events and mortality (3434. Kuznetsova T, Thijs L, Knez J, Herbots L, Zhang Z, Staessen JA. Prognostic value of left ventricular diastolic dysfunction in a general population. J Am Heart Assoc. 2014;3(3):e000789. https://doi.org/10.1161/JAHA.114.000789
https://doi.org/10.1161/JAHA.114.000789...
,3535. Wang JN, Biering-Sørensen T, Jørgensen PG, Jensen JS, Mogelvang R. Left ventricular filling pressure by septal and lateral E/e′ equally predict cardiovascular events in the general population. Int J Cardiovasc Imaging. 2017;33(5):653-61. https://doi.org/10.1007/s10554-016-1052-4.
https://doi.org/10.1007/s10554-016-1052-...
).

LA enlargement is a highly valued finding in echocardiography, which provides supportive evidence of structural alteration(s) of the heart. It is a parameter of LVDD and has been considered a predictor of cardiovascular events, HF, arrhythmias (atrial fibrillation), and mortality (2020. Bombelli M, Facchetti R, Cuspidi C, Villa P, Dozio D, Brambilla G, et al. Prognostic significance of left atrial enlargement in a general population results of the PAMELA study. Hypertension. 2014;64(6):1205-11. https://doi.org/10.1161/HYPERTENSIONAHA.114.03975.
https://doi.org/10.1161/HYPERTENSIONAHA....

21. Armstrong AC, Liu K, Lewis CE, Sidney S, Colangelo LA, Kishi S, et al. Left atrial dimension and traditional cardiovascular risk factors predict 20-year clinical cardiovascular events in young healthy adults: the CARDIA study. Eur Hear J Cardiovasc Imaging. 2014;15(8):893-9. https://doi.org/10.1093/ehjci/jeu018.
https://doi.org/10.1093/ehjci/jeu018...

22. Kizer JR, Bella JN, Palmieri V, Liu JE, Best LG, Lee ET, et al. Left atrial diameter as an independent predictor of first clinical cardiovascular events in middle-aged and elderly adults: the Strong Heart Study (SHS). Am Heart J. 2006;151(2):412-8. https://doi.org/10.1016/j.ahj.2005.04.031.
https://doi.org/10.1016/j.ahj.2005.04.03...

23. Laukkanen JA, Kurl S, Eränen J, Huttunen M, Salonen JT. Left atrium size and the risk of cardiovascular death in middle-aged men. Arch Intern Med. 2005;165(15):1788-93. https://doi.org/10.1001/archinte.165.15.1788.
https://doi.org/10.1001/archinte.165.15....
-2424. Tsang TS, Barnes ME, Gersh BJ, Takemoto Y, Rosales AG, Bailey KR, et al. Prediction of risk for first age-related cardiovascular events in an elderly population: the incremental value of echocardiography. J Am Coll Cardiol. 2003;42(7):1199-205. https://doi.org/10.1016/S0735-1097(03)00943-4.
https://doi.org/10.1016/S0735-1097(03)00...
). Froehlich et al. (3636. Froehlich L, Meyre P, Aeschbacher S, Blum S, Djokic D, Kuehne M, et al. Left atrial dimension and cardiovascular outcomes in patients with and without atrial fibrillation: a systematic review and meta-analysis. Heart. 2019;105(24):1884-91. https://doi.org/10.1136/heartjnl-2019-315174.
https://doi.org/10.1136/heartjnl-2019-31...
) found that LA enlargement is associated with cardiovascular outcomes in patients with and mainly without atrial fibrillation. According to the authors, LA myopathy is the main cause of these results. This study reinforces our finding that LA enlargement is significantly associated with cardiovascular events in individuals without previous cardiovascular diseases.

Concerning aortic root dilation, our results are consistent with those of the Framingham Heart Study cohort (3737. Lam CS, Gona P, Larson MG, Aragam J, Lee DS, Mitchell GF, et al. Aortic root remodeling and risk of heart failure in the Framingham Heart study. JACC Hear Fail. 2013;1(1):79-83. https://doi.org/10.1016/j.jchf.2012.10.003.
https://doi.org/10.1016/j.jchf.2012.10.0...
) which found that aortic root remodeling was associated with the risk of HF with reduced ejection fraction.

An important contribution of our review stems from the fact that echocardiographic abnormalities were diagnosed using simple and widely available methods (Table S3). Thus, these parameters can be used to assess the risk of cardiovascular outcomes in most echocardiography services without requiring more sophisticated techniques, benefiting a larger number of patients.

The findings of this study may have important implications for clinical practice because it increases awareness that individuals with echocardiographic abnormalities, even those who are asymptomatic and without previous diseases, should be monitored more carefully.

Two questions are presented here for discussion. LVH, LVDD, LA enlargement and also aortic dilation often occur together, and it is not possible to separate in a meta-analysis study like ours, the weight and independence of each of these parameters, as well as the association of some of them, on future cardiovascular disease events. Studies are needed to create a risk score associated with these factors. Another problem is that many of the studies that make up this meta-analysis used the m-mode to estimate the mass, measure the LA and the diameter of the aortic root. Likewise, for the diastolic function, some studies did not use tissue Doppler and other criteria according to the new guidelines. Therefore, it is possible that using more recent validated methods, different predictive values, and perhaps more significant RRs, can be found.

Currently, the concept of multimodal imaging has become increasingly reinforced (3838. de Lemos JA, Ayers CR, Levine BD, deFilippi CR, Wang TJ, Hundley WG, et al. Multimodality Strategy for Cardiovascular Risk Assessment: Performance in 2 Population-Based Cohorts. Circulation. 2017;135(22):2119-32. https://doi.org/10.1161/CIRCULATIONAHA.117.027272.
https://doi.org/10.1161/CIRCULATIONAHA.1...
). Two important biomarkers/predictors of cardiovascular risk are the coronary artery calcium score and the ratio of carotid artery intima-media thickness/atherosclerotic plaques (3939. Nakanishi R, Li D, Blaha MJ, Whelton SP, Darabian S, Flores FR, et al. All-cause mortality by age and gender based on coronary artery calcium scores. Eur Heart J Cardiovasc Imaging. 2016;17(11):1305-14. https://doi.org/10.1093/ehjci/jev328.
https://doi.org/10.1093/ehjci/jev328...
,4040. Gepner AD, Young R, Delaney JA, Budoff MJ, Polak JF, Blaha MJ, et al. Comparison of Carotid Plaque Score and Coronary Artery Calcium Score for Predicting Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc. 2017;6(2):e005179. https://doi.org/10.1161/JAHA.116.005179
https://doi.org/10.1161/JAHA.116.005179...
). It is necessary to investigate whether some of the echocardiographic parameters described here using appropriate methods are additive for these biomarkers/predictors.

Our study had some limitations. First, the reviewed articles used different echocardiographic approaches, thus increasing heterogeneity in the meta-analysis. Second, only 9 of 22 studies could be selected for meta-analysis, as there were few studies addressing the same exposure or with the same outcomes that could be grouped in the same meta-analysis. In this sense, further research is warranted to assess the contribution of echocardiography in monitoring asymptomatic patients without known previous cardiovascular events.

CONCLUSIONS

This systematic review and meta-analysis revealed that LVH, LVDD, LA enlargement, and aortic root dilation were associated with an increased risk of adverse cardiovascular outcomes in individuals without known cardiovascular diseases. These findings are important because they confirm the clinical value of monitoring patients with echocardiographic abnormalities to prevent major cardiovascular events, using simple data obtained on conventional echocardiography, even if further studies using more homogeneous methods, populations, and outcomes are still needed.

ACKNOWLEDGMENTS

CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior).

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APPENDIX   SUPPLEMENTARY MATERIAL

Table S1
The full search strategy MEDLINE/PUBMED. No Language, article type, or publication date restrictions.

Table S2
The Newcastle-Ottawa Quality Assessment Scale for cohort studies.
Table S3
Methods used to assess echocardiographic abnormalities, cardiovascular outcomes and risk found in the selected studies.

Publication Dates

  • Publication in this collection
    28 June 2021
  • Date of issue
    2021

History

  • Received
    14 Jan 2021
  • Accepted
    24 May 2021
Creative Common - by 4.0
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