Heart Diseases of Uncertain Etiology: Epidemiological Observations Compared with Clinical Experience

Main Article Content

Paolo Emilio Puddu, Prof. Alessandro Menotti, Prof.

Abstract

Backgrounds and Aims: Simple, long-term epidemiological observations allowed to identify a heterogeneous group of heart diseases manifested only as heart failure, arrhythmia and blocks in the absence of typical coronary syndromes, that we arbitrarily called initially atypical Coronary Heart Disease (CHD) and then Heart Disease of Uncertain Etiology (HDUE) in 12 published investigations.


Methods and Results: This group of heart diseases covered about 20% of all CVD mortality and about 10% of all-cause mortality in population cohorts close to extinction and compared with typical CHD was characterized by a strong association with age and the absence or an inverse association with serum cholesterol, dietary habits and physical activity. Moreover, HDUE appeared at an older age and had a higher age at death. Blood pressure and smoking habits (the latter with some uncertainties) were directly associated with the disease. Old pathology findings had already segregated the large myocardial scars due to gross atheroma of coronary arteries from small multiple sclerotic/fibrotic scars that seem independent and unrelated to coronary atheroma.


Conclusion: Etiology of HDUE, although probably multiple, is still vague and elusive, and the Literature was little informative about its relative frequency and possible causality. Future investigations might be stimulated by this review. To segregate HDUE from CHD should be important to correctly assess relationships among multiple risk factors and differential or condensed outcomes.

Keywords: Atypical CHD, HDUE, risk factors, age at death, outcome, etiology

Article Details

How to Cite
PUDDU, Paolo Emilio; MENOTTI, Alessandro. Heart Diseases of Uncertain Etiology: Epidemiological Observations Compared with Clinical Experience. Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2981>. Date accessed: 24 nov. 2024. doi: https://doi.org/10.18103/mra.v10i9.2981.
Section
Research Articles

References

1.Keys A (ed), Blackburn H, Menotti A, Buzina R, Mohacek I, Karvonen MJ, Punsar S, Aravanis C, Corcondilas A, Dontas AS, Lekos D, Fidanza F, Puddu V, Taylor HL, Monti M, Kimura N, Van Buchem FSP, Djordjevic BS, Strasser T, Anderson JT, Den Hartog C, Pekkarinen M, Roine P, Sdrin H. Coronary heart disease in seven countries. Circulation 1970; 41 (suppl 1): 1-211.
2.Keys A (ed), Aravanis C, Blackburn H, Buzina R, Djordjevic BS, Dontas AS, Fidanza F, Karvonen MJ, Kimura N, Menotti A, Mohacek I, Nedeljkovic S, Puddu V, Punsar S, Taylor HL, Van Buchem F. Seven Countries Study. A multivariate analysis of death and coronary heart disease. Harvard Univ Press, Cambridge Mass 1980, 1-381.
3.Kromhout D, Menotti A, Blackburn H. Prevention of coronary heart disease. Diet, lifestyle and risk factors in the Seven Countries Study. Kluwer Publ. Norwell Ma, USA and Dordrecht, NL, 2002: 1-267.
4.Menotti A, Blackburn H, Seccareccia F, Kromhout D, Nissinen A, Karvonen M, Fidanza F, Giampaoli S, Buzina R, Mohacek I, Nedeljkovic S, Aravanis C, Dontas A. Relationship of some risk factors with typical and atypical manifestations of coronary heart disease. Cardiology 1998; 89: 59-67.
5.Menotti A, Lanti M, Maiani G, Kromhout D. Forty-year mortality from cardiovascular diseases and their risk factors in men of the Italian rural areas of the Seven Countries Study. Acta Cardiol 2005; 60: 521-531.
6.Menotti A, Lanti M, Nedeljkovic S, Nissinen A, Kafatos A, Kromhout D. The relationship of age, blood pressure, serum cholesterol and smoking habits with the risk of typical and atypical coronary heart disease death in the European cohorts of the Seven Countries Study. Int J Cardiol 2005; 106: 157-163.
7.Menotti A, Puddu PE, Lanti M, Kromhout D, Tolonen H, Parapid B, Kircanski B, Kafatos A, Adachi H. Epidemiology of typical coronary heart disease versus heart disease of uncertain etiology (atypical) fatalities and their relationships with classic coronary risk factors. Int J Cardiol 2013; 168: 3963-3967.
8.Puddu PE, Terradura Vagnarelli O, Mancini M, Zanchetti A, Menotti A. Typical and atypical coronary heart disease deaths and their different relationships with risk factors. The Gubbio residential cohort Study. Int J Cardiol 2014; 173: 300-304.
9.Menotti A, Puddu PE. Lifetime prediction of coronary heart disease and heart disease of uncertain etiology in a 50-year follow-up population study. Int J Cardiol 2015; 196: 55-60.
10.Puddu PE, Menotti A. Natural history of coronary heart disease and heart disease of uncertain etiology: findings from a 50-year population study. Int J Cardiol 2015; 197: 260-264.
11.Menotti A, Puddu PE, Maiani G, Catasta G. Lifestyle behaviour and lifetime incidence of heart diseases. Int J Cardiol 2015; 201: 293-299.
12.Menotti A, Puddu PE, Maiani G, Catasta G. Cardiovascular and other causes of death as a function of lifestyle in a quasi-extinct middle-aged male population. A 50-year follow-up study. Int J Cardiol 2016; 201:173-178.
13.Puddu PE, Piras P, Menotti A. Lifetime competing risks between coronary heart disease mortality and other causes of death during 50 years of follow-up. Int J Cardiol 2017; 228: 359-363.
14.Menotti A, Puddu PE, Tolonen H, Adachi H, Kafatos A, Kromhout D. Age at death of major cardiovascular diseases in 13 cohorts. The seven countries study of cardiovascular diseases 45-year follow-up. Acta Cardiol 2019; 74: 66-72.
15.Menotti A, Puddu PE. Epidemiology of heart disease of uncertain etiology: a population study and review of the problem. Medicina 2019; 55: 687.
16.Puddu V, Menotti A. Unsicherheit der Grenzen und diagnostichen Kriterien der ischaemischen Kardiopathie. Arzt Forsch 1965, 19: 175-179.
17.WHO International Classification of Diseases (WHO-ICD-9) World Health Organization. International classification of diseases and causes of death. 9th Revision. Geneva: WHO; 1975.
18.WHO International Classification of Diseases (WHO-ICD-10) International Statistical Classification of Diseases and Related Health Problems, 10th Revision. Geneva: WHO; 1992.
19.WHO International Classification of Diseases (WHO-ICD-8) World Health Organization. International classification of diseases and causes of death. 8th Revision. Geneva: WHO; 1965
20.Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55000 vascular deaths. Lancet 2007; 370: 1829-1839.
21.WEB Site. Verbal Autopsy Standards. The 2012 WHO Verbal Autopsy Instruments. Release Candidate 1, WHO, Geneva, February 2015 (Visited).
22.Classification des Lésions d’athérosclerose. Organization Mondiale de la Santé. Rep Techn Ser n:143. 1958
23.Hypertension and Coronary Heart Disease. Classification and Criteria for Epidemiological Studies. World Health Organization. Rep Techn Ser n:168, 1959.
24.Burgess AM, Feifar Z, Kagan A. Hypertension arterielle et cardiopathie ischémiques. Comparibilité des études epidemiologiques. Organizaion Mondiale de la Santé, Geneve, 1963.
25.Nomenclature and criteria for diagnosis of ischemic heart disease. Report of the Joint International Society of Cardiology and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Circulation 1979;59: 607-609.
26.Bartel A, Heyden S, Tyroler HA, Tabesh E, Cassel JC, Hames CG. Electrocardiographic predictors of coronary heart disease. Arch Intern Med 1971; 128: 929-937.
27.Schwartz CJ, Mitchell JR. The relation between myocardial lesions and coronary artery disease. i. An unselected necropsy study. Br Heart J 1962; 24: 761-786.
28.Mitchell JR, Schwartz CJ. The relation between myocardial lesions and coronary artery disease ii. A selected group of patients with massive cardiac necrosis or scarring. Br Heart J 1963; 25: 1-24.
29.Anonimous. Myocardial Fibrosis. Br Med J 1963; 1(5341): 1304.
30.Bernecker OY, Huq F, Heiat EK, Podesser BK, Hajjar RJ. Apoptosis in heart failure and the senescent heart. Cardiovasc Toxicol 2003; 3: 183-190.
31.Murdoch DR, Love MP, Robb SD, McDonagh TA, Davie AP, Ford I, Capewell S, Morrison CE, McMurray JJ. Importance of heart failure as a cause of death. Changing contribution to overall mortality and coronary heart disease mortality in Scotland 1979-1992. Eur Heart J 1998; 19: 1829-1835.
32.Mendy VL, Vargas R, Payton M. Trends in mortality rates by subtypes of heart disease in Mississippi, 1980-2013. BMC Cardiovasc Disord 2017; 17: 158.
33.Fabbri G, Gorini M, Maggioni AP, Cacciatore G, Di Lenarda A. [Italian Network on Congestive Heart Failure: ten-year experience].[Article in Italian] G Ital Cardiol (Rome) 2006; 10: 689-694.
34.Parameshwar J, Shackell MM, Richardson A, Poole-Wilson PA, Sutton GC. Prevalence of heart failure in three general practices in north west London. Br J Gen Pract 1992; 42: 287-289.
35.Mair FS, Crowley TS, Bundred PE. Prevalence, aetiology and management of heart failure in general practice. Br J Gen Pract 1996; 46:77-79.
36.Dawber TR. The Framingham Study. The epidemiology of atherosclerotic disease. Harward Univ Press, Cambradge Mass, USA, and London England. 1980: 1-257.
37.Kannel WB. Vital epidemiologic clues in heart failure. J Clin Epidemiol 2000; 53: 229-235.
38.Remes J, Reunanen A, Aromaa A, Pyörälä K. Incidence of heart failure in eastern Finland: a population-based surveillance study. Eur Heart J 1992; 13: 588-593.
39.Mahmood SS, Levy D, Vasan RS, Wang TJ. The Framingham Heart Study and the epidemiology of cardiovascular diseases: a historical perspective. Lancet 2014; 383: 999-1008.
40.Mayosi BM. Contemporary trends in the epidemiology and management of cardiomyopathy and pericarditis in sub-Saharan Africa. Heart 2007; 93: 1176-1183.
41.Falase AO, Ogah OS. Cardiomyopathies and myocardial disorders in Africa: present status and the way forward. Cardiovasc J Afr 2012; 23: 552-562.
42.Sliwa K, Mayosi BM. Recent advances in the epidemiology, pathogenesis and prognosis of acute heart failure and cardiomyopathy in Africa. Heart 2013; 99: 1317-1322.
43.Kwan GF, Jean-Baptiste W, Cleophat P, Leandre F, Louine M, Luma M , Benjamin EJ , Mukherjee JS, Bukhman G, Hirschhorn LR. Descriptive epidemiology and short-term outcomes of heart failure hospitalisation in rural Haiti. Heart 2016; 102: 140-146.
44.Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile of heart failure. Nat Rev Cardiol 2011; 8: 30-41.
45.Khatibzadeh, S, Farzadfar F, Oliver J, Ezzati M, Moran A. Worldwide risk factors for heart failure: a systematic review and pooled analysis. Int J Cardiol 2013; 168: 1186-1194.
46.Ho KKL, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol 1993; 22 (Suppl. A1): A6-A13.
47.Gottdiener JS, Arnold AM, Aurigemma GP, Polak JF, Tracy RP, Kitzman DW, Gardin JM, Rutledge JE, Boineau R.. Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study. J Am Coll Cardiol 2000; 35: 1628-1637.
48.Wilhelmsen L, Rosengren A, Eriksson H, Lappas G. Heart failure in the general population of men. Morbidity, risk factors and prognosis. J Intern Med 2001; 106: 3068-3072.
49.Nago N, Ishikawa S, Goto T, Kayaba K. Low cholesterol is associated with mortality from stroke, heart disease, and cancer: the Jichi Medical School Cohort Study. J Epidemiol 2011; 21: 67-74.
50.Horwich TB, Hamilton MA, Maclellan WR, Fonarow GC. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 2002; 8: 216-224.
51.Rauchhaus M, Clark AL, Doehner W, Davos C, Bolger A, Sharma R, Coats AJ, Anker SD. The relationship between cholesterol and survival in patients with chronic heart failure. J Am Coll Cardiol 2003; 42: 1933-1940.
52.Sakatani T, Shirayama T, Suzaki Y, Yamamoto T, Mani H, Kawasaki T, Sugihara H, Matsubara H. The association between cholesterol and mortality in heart failure. Comparison between patients with and without coronary artery disease. Int Heart J 2005; 46: 619-629.
53.Afsarmanesh N, Horwich TB, Fonarow GC. Total cholesterol levels and mortality risk in non-ischemic systolic heart failure. Am Heart J 2006; 152: 1077-1083.
54.Skwarek M, Bilińska ZT, Mazurkiewicz Ł, Grzybowski J, Kruk M, Kurjata P, Piotrowski W, Ruzyłło W. Significance of dyslipidaemia in patients with heart failure of unexplained aetiology. Kardiol Pol 2008; 66: 515-522.
55.Yoon CH, Youn TJ, Ahn S, Choi DJ, Cho GY, Chae IH, Choi J, Cho H, Han S, Cho MC, Jeon ES, Chae SC, Kim JJ, Ryu KH, Oh BH. Low serum total cholesterol level is a surrogate marker, but not a risk factor, for poor outcome in patients hospitalized with acute heart failure: a report from the Korean Heart Failure Registry. J Card Fail 2012; 18: 194-201.
56.Greene SJ, Vaduganathan M, Lupi L, Ambrosy AP, Mentz RJ, Konstam MA, Nodari S, Subacius HP, Fonarow GC, Bonow RO, Gheorghiade M, EVEREST Trial Investigators. Prognostic significance of serum total cholesterol and triglyceride levels in patients hospitalized for heart failure with reduced ejection fraction (from the EVEREST Trial). Am J Cardiol 2013; 111: 574-581.
57.Kahn MR, Kosmas CE, Wagman G, Serrao GW, Fallahi A, Grady KM, Vittorio TJ.. Low-density lipoprotein levels in patients with acute heart failure. Congest Heart Fail 2013; 19: 85-91.
58.Bluemke DA. MRI of nonischemic cardiomyopathy. Am J Roentgenol. 2010; 195: 935-940.
59. Follath F. Ischemic versus non-ischemic heart failure: should the etiology be determined? Heart Fail Monit 2001; 1: 122-125.
60.Florian A, Ludwig A, Stubbe-Dräger B, Boentert M, Young P, Waltenberger J, Rösch S, Sechtem U, Yilmaz A. Characteristic cardiac phenotypes are detected by cardiovascular magnetic resonance in patients with different clinical phenotypes and genotypes of mitochondrial myopathy. J Cardiovasc Magn Reson 2015; 17: 40.
61.Moolman-Smook JC, Mayosi BM, Brink PA, Corfield VA. Molecular genetics of cardiomyopathy: changing times, shifting paradigms. Cardiovasc J South Afr 2003; 14: 145-155.
62.Asakura M, Kitakaze M. Global gene expression profiling in the failing myocardium. Circ J 2009; 73: 1568-1576.
63.Laonigro I, Correale M, Di Biase M, Altomare E. Alcohol abuse and heart failure. Eur J Heart Fail 2009; 11: 453-462.
64.Schoppet M, Maisch B. Alcohol and the heart. Herz 2001; 26: 345-52.
65.Aquaro GD, Gabutti A, Meini M, Prontera C, Pasanisi E, Passino C, Emdin M, Lombardi M. Silent myocardial damage in cocaine addicts. Heart 2011; 97: 2056-2062.
66.Chung YR, Park SJ, Moon KY, Choi SA, Lim HS, Park SW, Kim JH, Lee K. Diabetic retinopathy is associated with diastolic dysfunction in type 2 diabetic patients with non-ischemic dilated cardiomyopathy. Cardiovasc Diabetol 2017; 16: 82.
67.Cubbon RM, Adams B, Rajwani A, Mercer BN, Patel PA, Gherardi G, Gale CP, Batin PD, Ajjan R, Kearney L, Wheatcroft SB, Sapsford RJ, Witte KK, Kearney MT. Diabetes mellitus is associated with adverse prognosis in chronic heart failure of ischaemic and non-ischaemic aetiology. Diab Vasc Dis Res 2013; 10: 330-336.