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Review

The Epidemiology of Isolated (Independent) Heart Failure Is Still Looking for Authors?

by
Paolo Emilio Puddu
1,2,* and
Alessandro Menotti
1
1
Association for Cardiac Research, 00182 Rome, Italy
2
EA 4650, Signalisation, Électrophysiologie et Imagerie des Lésions D’ischémie Reperfusion Myocardique, Normandie Université, UNICAEN, 14000 Caen, France
*
Author to whom correspondence should be addressed.
J. Vasc. Dis. 2025, 4(3), 30; https://doi.org/10.3390/jvd4030030
Submission received: 12 May 2025 / Revised: 15 July 2025 / Accepted: 5 August 2025 / Published: 8 August 2025
(This article belongs to the Section Cardiovascular Diseases)
Versions Notes

Abstract

The concepts of “isolated” or “idiopathic” heat failure (CHF/HF) and more recently of “non-dilated cardiomyopathy” lack a clear description of the specific characteristics that help condense the disease into a nomenclature-based list applicable to population studies. This ensued in the absence of primary preventive investigations of CHF/HF. Moreover, in the large spectrum of cardiovascular diseases (CVD), the conditions attributable to coronary heart diseases (CHD) from those related to CHF/HF or other causes are not in general disentangled. We review here current results prompting the operational idea to index heart diseases of uncertain etiology (HDUEs) from a population-based perspective in several contributions, where CHF/HF represented 50% of HDUEs, approximately 10% of all CVD mortality and approximately 5% of all-cause mortality. We wish to stimulate new studies that compare CHD with CHF/HF only, exploiting population data, excluding baseline prevalent heart diseases, including incidence cases and separately studies with large numbers of recruited individuals. These analyses may well be complemented by the use of the Fine-Gray variant of the Cox predictive model that, by the sub-distribution of hazard models, may enable identifying risk factors as the determinants of competition between groups of diseases. The aim is to better define the differences between CHD and CHF/HF along with the possible etiology and even specific risk factors of these independent CHF/HF cases. A surge of interest among the investigators should thus be stimulated. Eventually, also for this “character” (in Pirandello’s acception), an author may hopefully be found, thus complementing with etiology an apparently orphan condition.

1. Introduction

Each one of us have our own reality. Life is full of infinite absurdities, which, strangely enough, do not even need to appear plausible, because they are true. The trouble is that the absurd is always part of our reality, and though we do not recognize it as such, it comes to us with the terrible force of destiny [1]. More than a century has passed from the 1921 premiere of Pirandello’s drama titled “Six Characters in Search of an Author” at the Teatro Valle in Rome. The play rapidly became the landmark of modernist and absurdist theatre. Likewise, congestive heart failure (CHF), or just heart failure (HF), as a cardiovascular syndrome that can be a consequence or a complication occurring during the natural history of any kind of etiologically defined heart disease, is like a character in search of an author. Both in clinical and population research, cases of CHF/HF that seem isolated (or idiopathic) have been identified, more recently also referred to as “non-dilated cardiomyopathy”, i.e., not preceded nor accompanied by a definite heart disease, and the proper etiology and nomenclature are still undefined.
Looking into the literature and in particular into population studies, we aim to set the stage for future investigations with the primary goal of clarifying the characteristics of isolated (independent) CHF/HF, possibly also finding new risk factors, if not clear-cut etiologies. Indeed, the initial and dominant interests of cardiovascular epidemiologists were focused on coronary heart disease (CHD) as shown by some early major studies [2,3,4]. Only later was attention given to stroke and rather frequently to major cardiovascular diseases (CVD), unfortunately grouped altogether, disregarding the possible different etiologies of various groups and subgroups. Some grey areas were thus not considered and analyzed and a major aim here is to call attention to this in order to clarify the classification of CHD versus other heart disease forms (frequently confused with CHD) in very old analyses based on hospital or outpatient department data, where “painful” versus “not painful” cases represent the discrimination of CHD versus other forms frequently called “myocardial sclerosis”. Of special interest is the large difference between these two groups in these very old reports: serum cholesterol levels were definitely higher in the “painful” class [5,6]. An attempt to segregate these two groups was also made in the diagnostic criteria adopted in the mid-1900s by the research group of the Seven Countries Study of Cardiovascular Diseases (SCS) [7].
More recently, essentially for operational needs in field investigations in population studies where risk factors and mortality data were accrued during long-term follow-up, an attempt was made to segregate “typical” CHD (myocardial infarction, acute ischemic attacks, and sudden coronary death) from other heart diseases frequently confused with typical CHD. The initially categorized “atypical” CHD group was later called heart disease of uncertain etiology (HDUE). This combined symptomatic heart disease (heart failure, chronic arrhythmia, blocks, covering approximately 65% of total), hypertensive heart disease (usually in the absence of a clear left ventricular hypertrophy, covering approximately 15%) and chronic and other ischemic heart disease with characteristics that did not meet typical CHD syndromes (covering approximately 20%). Overall CHF/HF, considered separately, covered approximately 50% of all HDUE cases. Importantly, in male residential cohorts with a long follow-up close to extinction, HDUE cases covered approximately 20% of all CVD mortality and approximately 10% of all-cause mortality. HDUE thus had a large impact on population outcomes.
Analyses on HDUE, usually opposed against CHD, were run on different studies like the Italian Rural Areas (IRA) of the Seven Countries Study [8,9], the whole SCS with its 16 cohorts [10,11], the Gubbio Population Study [12] (the only one also including women) and the Italian RIFLE Project [13]. Systematically, similar findings were found in all analyses and studies, and in particular [13]: (a) age of first event was lower in CHD than in HDUE; (b) age at death was lower for CHD than for HDUE; (c) in the late part of long follow-up, with subjects increasing their age until reaching extinction of cohorts, death rates from HDUE, initially lower, overtook those of CHD; (d) a strong, significant and direct association between serum cholesterol was found for CHD, but not for HDUE—the inverse association of HDL cholesterol was found for CHD but not for HDUE; (e) the Mediterranean Diet and vigorous physical activity had a protective role for CHD but not for HDUE [14].
The overall findings, here condensed in Table 1 [8,9,10,11,12,13,14,15,16,17], suggested that CHD and HDUE are probably two different diseases, or at least conditions (“Characters” in the Pirandollo’s acception and term [1]) with different relationships with some risk factors and different natural histories. More recently, using competing risk analyses run using the Cox variant called Fine-Gray modelling, CHD versus HDUE were challenged and the role of serum cholesterol as a possible determinant for the difference between the two end-points was observed [18,19,20].

2. Comparison with the Literature

It is practically impossible to compare the results condensed in Table 1 with those of the concurring literature in the population study areas—first, because the concept of HDUE was not popular and then because we systematically made a comparison with typical CHD syndromes as a counterpart. As the most common components of HDUE were CHF/HF, with approximately 50% of cases, we tried to identify, mainly among studies reporting on population investigations, the potential risk factors which may be tied to causality. However, the literature presents CHF/HF in a strange and not homogeneous way, since it is frequently considered a disease termed “isolated” or “idiopathic” CHF/HF or “non-dilated cardiomyopathy”, in the absence of any clearly defined etiology, and not a pathophysiologic step or complication that may occur in the natural history of any type of etiologically defined heart disease. The major related problems stem from a series of subproblems that explain why CHF/HF investigations at the epidemiologic level are so rare:
Nomenclature. In the past, there were formal suggestions from working groups on how to differentiate various types of heart disease, mainly CHD from other forms of “degenerative” or “arteriosclerotic” heart diseases. Various working groups, mainly led by the World Health Organization [21,22,23,24], tried to reach valuable proposals for classifying heart diseases mainly for epidemiological purposes considering the possible different etiologies of CHF/HF. Although several proposals were made, substantial uncertainties remain, leaving the lack of a clear segregation of typical CHD from other forms. The location, borders and extent of isolated (independent) CHF/HF were never clearly defined.
Other sources of confusions came from the WHO classification of Diseases and Causes of Death. Just referring to the 8th, 9th and 10th revisions of that classification [25,26,27], the chapter on CHD (or IHD: ischemic heart disease) contains some rather vague and not well-defined components such as Chronic Ischemic and Other Forms of IHD, the meaning of which could not be understood, although frequently used in the death certificates and clinical diagnoses. It is unknown what signs, symptoms, etc. (arrhythmia, heart failure, blocks?), characterize these subgroups (Table 2). Even for research purposes, such subgroups were maintained as part of CHD, ignoring and never having tested the fact that they are not associated with high serum cholesterol and characterized by different natural histories. Another problem is the fact that too many analyses include all CVDs as end-points (except Congenital Heart Diseases since they are classified in the Chapter of Congenital Malformations) simply because they belong to the same anatomic–physiologic system, disregarding the fact that risk factors, causes and clinical manifestations could be largely different in the various subgroups. It would be the same to study the causes of digestive system diseases from mouth to rectum, again because all of them belong to the same system.
In relation to CHD: The many specifications given by the ICD-10 are largely related to anatomical details. In the three ICDs, the chapters on Chronic and Other (types) give several indications that are vague and difficult to translate into a clinical diagnosis. Chronic and Other types are part of our HDUE definitions, not (or even negatively) associated with serum cholesterol. This notion is not well known and this impairs the relationships of serum cholesterol with CHD, that is with the main risk factor of this condition.
In relation to (congestive) heart failure: The three ICDs are almost equal. A problem arises when the term heart failure is used in a clinical diagnosis or a cause of death. In fact, if heart failure is the first (or the only) mentioned condition, we should assume that the heart disease causing heart failure is not known, while if heart failure precedes an etiologically defined heart disease, the sequence represents a mistake, because the correct sequence must be the inverse one. Isolated cases of heart failure are part of our HDUE definitions, not (or even negatively) associated with serum cholesterol, tending to exclude an ischemic origin.
An example of the bad use of the International Classification derives from a large meta-analysis of serum cholesterol versus CVD mortality with more than 900,000 subjects involved [28]. The various end-points included CHD (ICD-9 codes 410–414 plus all possible cases of sudden death), all types of cerebrovascular diseases, and all other possible CVD events classified in the chapter on CVD in the International Classification. The fact that there are subgroups where, within each group relationships with serum cholesterol do not exist or might be even inverse, was disregarded. The consequence is that, in each big group of diseases, cases with a numerical majority may lead to the assumption that all subgroups behave in the same way versus risk factors and possible causes.
Size of the problem. It is acknowledged that CHF/HF is mainly a problem of elderly subjects [29] but a distinction between CHF/HF due to other defined heart disease and isolated cases is rarely found. In a series of clinical and population studies performed in Western countries, it appears that the majority of CHF/HF cases are a consequence of CHD [2,30,31,32,33,34,35,36,37], while cases declared of unknown origin range from 15 to 37%. Careful investigations about the possible risk factors or causes of this group cannot be found except the frequent assertion that systolic blood pressure is common and important risk factor.
Pathophysiology and clinics versus epidemiology. Clinicians know well what CHF/HF is when looking at hospitalized patients or outpatients since they are able to diagnose or appreciate CHF/HF as a complex clinical syndrome resulting from structural or functional impairment of ventricular filling or ejection of blood involving a cascade of neurohormonal and hemodynamic alterations that progressively impair cardiac function. In other terms, they look at the maladaptive response to myocardial injury, including neurohumoral activation, fluid retention, and ventricular remodeling [38], but rapidly see that these initially compensatory processes ultimately worsen cardiac performance and systemic function. Using various technologically complex or expensive means, they measure ventricular remodeling as a hallmark of CHF/HF, involving cardiomyocyte hypertrophy, apoptosis, and interstitial fibrosis along with activation of neurohormonal systems, particularly the renin–angiotensin–aldosterone system (RAAS) and the sympathetic nervous system (SNS). As emphasized in the 2023 European Society of Cardiology (ESC) guidelines, “persistent neurohormonal activation exerts deleterious effects, promoting myocardial fibrosis, apoptosis, and impaired calcium handling” [39]. Inflammation and oxidative stress further exacerbate cardiac dysfunction. Moreover, using echocardiography in particular, CHF/HF patients with preserved ejection fraction (HFpEF) may be disentangled: systemic inflammation may be clearly central in these cases and coronary microvascular dysfunction and myocardial stiffening may result, underpinning diastolic dysfunction [40]. HFpEF pathophysiology may also be distinguished from that of HFrEF (presenting with reduced ejection fraction), based on this inflammatory process underscoring its systemic nature. Other than the cardiovascular system may be compromised in CHF/HF: cardiorenal interactions, skeletal muscle wasting, and metabolic derangements contribute significantly to disease burden. CHF/HF for clinicians is thus not solely a cardiac disorder but a systemic syndrome involving multi-organ impairment [41].
Cardiovascular epidemiologists are confronted only with classic CHF/HF symptoms including dyspnea, fatigue, exercise intolerance, and fluid retention, which collectively reflect impaired cardiac output and elevated filling pressures [42]. Dyspnea is the most frequent symptom, often reported during exertion but progressing to orthopnea or paroxysmal nocturnal dyspnea as congestion worsens. Edema, especially peripheral in the lower limbs, and weight gain indicate systemic venous congestion, particularly in right-sided CHF/HF. However, they may not use radiography or echocardiography, nor more sophisticated means to the extent that they may not directly appreciate pulmonary congestion nor nonspecific and subtle signs that, particularly in elderly patients or those with HFpEF [38], may relate to fatigue and reduced exercise capacity, reflecting diminished perfusion of skeletal muscles and peripheral tissues. Therefore, these symptoms, particularly debilitating and also often underestimated in clinical assessment, may remain underestimated in field population studies since a high index of suspicion may only follow objective testing for confirmation [43].
A number of key signs of CHF/HF may be disclosed by simple physical examination: elevated jugular venous pressure, third heart sound (S3), pulmonary crackles, hepatomegaly, and dependent edema. All these signs may also be taken into consideration in population studies. In acute decompensation, tachycardia, hypotension, and signs of hypoperfusion (e.g., cold extremities and altered mental status) may predominate. Clinical classifications like the New York Heart Association (NYHA) functional class and Forrester hemodynamic subsets provide practical frameworks for assessment and management [44]. Importantly, the clinical picture may differ in HFpEF, where patients often present with exertional dyspnea and signs of volume overload, but with preserved systolic function. These patients are frequently older, female, and have multiple comorbidities such as hypertension, atrial fibrillation, and obesity [45,46].
Thus, while CHF/HF presents with a recognizable constellation of signs and symptoms, the heterogeneity of clinical profiles demands a thorough and nuanced approach to diagnosis, one that combines symptom assessment with imaging, biomarkers, and functional testing. This is also why, lacking most of these tests, the correct diagnosis of CHF/HF may still be challenging, especially in population studies. In fact, most CVD epidemiology studies gave little and later attention to CHF/HF compared with CHD. Frequently, the description was confused and rarely clear cut in segregating cases due to defined CHF/HF from those with an unknown or uncertain origin.
Studies starting in the middle of the last century forcefully used relatively simple clinical symptoms and signs for the diagnosis of CHF/HF. For example, in the Seven Countries Study of Cardiovascular diseases, starting in 1958, the diagnosis was based on the presence of at least two of the following symptoms and signs: dyspnea, distended neck veins, basal lung crepitant rales, leg oedema, severe arrhythmia, enlarged heart, and gallop rhythm, all in the absence of other clear reasons [47]. These criteria were retained and reused in the long follow-up in order to maintain the comparability of findings. However, in between, clinical practice took advantage of new powerful diagnostic devices such as echocardiography, TAC, magnetic resonance, and oximetry. More recently, telemetry and teleassistance came into play with potential important impacts on self-reported outcome measurements [48,49]. We are unaware whether any comparison was ever made between symptoms and signs versus instrumentation or procedural and/or telemetric diagnostics to the extent that a mismatch may exist between CHF/HF cases diagnosed in the context of population investigations versus those obtained in clinical studies. Moreover, the tremendous increase in therapeutical drug efficacies now at hand contrasts with few and generally poorly active regimens in the middle of the last century when the epidemiological investigations were started.
Old pathology findings. Old pathology findings were clear cut in segregating different types of myocardial scars that had a bimodal distribution. In fact, large myocardial scars were bound to gross coronary atheroma while small multiple scars were not more common in cases of gross atheroma. The large scars were usually associated with myocardial infarction. The etiology of the small scars was only suspected. The multiple scars, likely leading to fibrosis, were interpreted as an induction of CHF/HF due to the diffuse damage of the myocardium [50,51]. Autoimmune processes were also hypothesized as causes of multiple small scars [52].
Risk factors. There is much confusion in the domain of CHF/HF risk factors [53,54] and quite a long list of not homogeneous characteristics including various etiologically defined conditions. Rheumatic and valvular diseases, myocardial infarction, obesity, diabetes, behavioral lifestyle habits such as smoking, eating and motion habits, dyslipidemia, hypertension, left ventricular hypertrophy, and carotid wall thickness are taken into account. Other findings derived from diagnostic devices and procedures such as x-rays, ECG, and echocardiography may create much confusion as they lead to the conclusion that most of the so discovered characteristics have an implied role as CHF/HF risk factors. The fact that CHF/HF is simply a consequence of the basic diseases that may occur in its natural history is thus ignored, while diagnostic findings are simply the collateral documentation of diagnosis. On the other hand, it is not clear whether all the other personal characteristics are considered risk factors of the underlying diseases or specifically of CHF/HF. This is a particularly serious shortcoming of primary preventive-oriented studies, where it is mandatory to start with apparently healthy individuals, not actually “patients” and thus all prevalent individuals should be removed. This is also why, in addition to the need for extremely long-term follow-up (well exceeding 30–40 years) to reach CHF/HF the top of incidence, there are essentially few studies exploring risk factors for CHF/HF in the area of residential cohorts.
In a group of valuable population studies from Sweden, USA, and Japan [55,56,57,58], the occurrence of CHF/HF was not associated with previous high cholesterol levels but rarely the distinction was found among CHD causes, other heart disease causes and unknown causes. In the Framingham Heart Study monograph published in 1980 and dealing with the first 24 years of follow-up [2], HF was unequivocally attributed to a group of conditions including high blood pressure, consequences of minor and major CHD events (angina pectoris and myocardial infarction), cigarette smoking, and obesity. Incidentally, in that book, it is suggested that the concept of hypertensive heart diseases should not be used, being a misnomer since it is impossible to exclude that left ventricular hypertrophy is not accompanied by the consequence of ischemic episodes. Moreover, there is no mention of possible cases of HF not accompanied or preceded by other morbid conditions except for hypothesizing the role of “senescence” as a possible cause of HF in the elderly.
Possible causes of CHF/HF. Among the possible causes of CHF/HF, several studies mentioned dyslipidemia, apoptosis, myocardial fibrosis, inflammation and related biomarkers. The concept of dyslipidemia is rather vague and its meaning is variable. When this factor is mentioned together with the presence of some other heart diseases, except CHD, it cannot be considered a cause nor even a risk factor. In a recent contribution from the Seven Countries Study research groups, it was showed, at ecological levels and across 16 cohorts of middle-aged men followed for up 50 to 60 years, that dietary atherogenicity and thrombogenicity indexes are directly and strongly related to CHD mortality, but not to HDUE [17,59]. The two indexes combine 8 to 10 dietary fatty acids comparing saturated fatty and trans fatty acids with mono- and poly-unsaturated fats. Since approximately half of HDUEs are CHF/HF, as alluded above, there are good reasons to believe that these indicators of dyslipidemia are also unrelated.
Apoptosis [60] is a physiological process that removes damaged cells, thus reducing the operative action of the damaged organ. This may well be a pathophysiological process promoting CHF/HF, but it cannot be defined as a cause because it is a consequence of previous damages due to known or unknown causes [61,62]. In fact, it is the process that substitutes small myocardial scars with fibrotic tissue, contributing to a reduced contractile efficiency of the heart. Although small myocardial scars are frequently considered as a consequence of minor ischemic attacks, including angina pectoris, the pathological evidence is that many diffuse small scars are not more common in cases of gross coronary atheroma, leading to hypothesize other real causes. Again, we face a pathophysiological process that cannot be considered a cause.
Another process that is frequently considered a cause of CHF/HF and other conditions like coronary atheroma is inflammation together with related indicators like C reactive protein [63,64,65,66,67]. However, inflammation is another pathophysiological process that is not specific and starts as a reaction to external causes, observed at the onset and progression of many morbid conditions. Among them there are some nutrients, like saturated fatty acids, and oligo-saccharides [68,69,70]. Again, mismatch and confusion exist between pathophysiological processes and causes, which usually are external and may induce the onset of those reactions.
CHF/HF and low serum cholesterol. Several clinical studies showed an association between CHF/HF and low serum cholesterol (at the time of observation) [71,72,73,74]. The fact is that serum cholesterol measured at the time of acquired diseases cannot be necessarily suspected as a risk factor since the time relationship with event is not respected. Moreover, few papers segregated cases with previous definite CHD syndromes, characterized by high serum cholesterol, from cases without this attribute showing that those of CHD origin definitely had higher serum cholesterol [73], and at least one group clearly alluded that low serum cholesterol is a surrogate marker, but not a risk factor of CHF/HF [74]. Finally, since CHF/HF are common in the elderly, problems of malnutrition might be, at least in part, the cause of low serum cholesterol levels and not necessarily a possible cause of CHF/HF.
Rare diseases as causes of CHF/HF. A few sparse contributions were concentrated on other heart diseases eventually inducing CHF/HF but with an etiology that is difficult to identify, usually representing rare cases of specific etiologies. They include the most variegated possible causes of heart disease including rare mitochondrial abnormalities [75], specific genes associated with CHF/HF and its severity [76,77], alcohol or cocaine addiction [78,79,80], and the influence of diabetes on CHF/HF [81,82]. All these cases may represent initially unknown etiologies, subsequently associated with clear etiologies, sometimes complex. The fact is that they are reported as limited clinical casuistics and their real frequency is undefined in a list of other characteristics that should be compared with those of CHD, which remains the reference.

3. Why Concentrate on CHF/HF in Future Population Studies?

From a population-based perspective, the three components of what we call HDUE [7,8,9,10,11,12,13,14,15,16,17,18,19,20] have similar characteristics despite likely different origins. When digging further into, we found that approximately 50% of cases can be classified as independent CHF/HF, that is cases without any evidence of a definite etiology. It should again be recalled that CHF/HF is a syndrome that can represent a pathophysiologic step in the natural history of any type of heart disease while cases of our interest, from the perspective of investigating risk factors and etiology, are only those where pre-existing clear heart diseases cannot be found.
These considerations and the indications condensed in Table 1 prompted the idea to conduct new analyses, comparing CHD with these cases of CHF/HF only, exploiting population data, excluding baseline prevalent heart disease, including incidence cases and separately studies with large numbers, needed considering that the final size of the CHF/HF should be approximately half of HDUEs. These analyses will be complemented by the use of the Fine-Gray variant of the Cox predictive model that, by the sub-distribution of hazard models, may allow risk factors to be identified as determinants of competition between groups of diseases. We thus hope to better define the differences between the two morbid conditions (CHD versus CHF/HF) well disentangled in the context of overall CVD that are generally (and unfortunately) confused concomitantly. The possible etiology and even specific risk factors of these independent CHF/HF cases are still unknown but the surge of interest among investigators should definitely be stimulated and we may contribute by the present essay.
Considering the confusion existing in nomenclature (Table 2), one may also fully disregard how these CHF/HF forms are referred to at present, either isolated or idiopathic heart failure or non-dilated cardiomyopathy, providing an author for this character may hopefully be found, thus complementing an apparently orphan condition with etiology.

Funding

This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.

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Table 1. Some examples of differences between CHD and HDUE. In population studies from our team, CHF/HF represents approximately 50% of HDUEs.
Table 1. Some examples of differences between CHD and HDUE. In population studies from our team, CHF/HF represents approximately 50% of HDUEs.
Study PopulationStudy VariableCHDHDUE
IRA 1712 men aged 40–59:
50 years of follow-up for incidence.
Individual analysis [8]		Age at first event68.9 (S)74.3 (NS)
IRA 1712 men aged 40–59:
61 years of follow-up for mortality. Individual analysis [15,16]		Age at death 61 years follow-up73.2 (S)79.7 (NS)
Serum cholesterolHR for 1 mmol/L=
1.22 (S)		HR for 1 mmol/L=
1.02 (NS)
Physical activityHR of vigorous versus sedentary physical activity = 0.85 (S)HR of vigorous versus sedentary physical activity = 0.88 (NS)
Mediterranean versus not Mediterranean DietHR = 0.67 (S)HR = 1.24 (NS)
SCS, 9704 men aged 40–59 in 13 cohorts of 7 countries:
40 years of follow-up for mortality.
Individual analysis [7].		Serum cholesterolHR for 40 mg/dL in North America and Europe 1.24 (S);
in Southern Europe
1.23 (S) 		HR for 40 mg/dL/in
North America and Europe 1.05 (NS);
in Southern Europe
1.04 (NS)
Gubbio Population Study
3329 men and women aged 30–79:
20 years of follow-up for mortality.
Individual analysis [12].		Serum cholesterolHR for 1 mmol/L=
1.29 (S)		HR for 1 mmol/L=
0.87 (NS)
Age at death
(however, only
20 years follow-up, not extinct)		72.0 (S)81.2 (NS)
SCS
16 men cohorts, aged 40–59:
50 years of follow-up for mortality.
Ecological analysis [17]		MAI:
high levels represent Mediterranean Diet		R = −0.91
(S)		R = 0.01
(NS)
ATI:
high levels represent excess of saturated and trans fats		R = 0.93
(S)		R = −0.02
(NS)
SCS = Seven Countries Study; IRA = Italian Rual Areas of SCS; HR = hazard ratio; R = correlation coefficient; MAI = Mediterranean Adequacy Index; ATI = Dietary Atherogenicity Index; (S) = significant; (NS) = not significant.
Table 2. Chapters and related numerical codes on coronary (ischemic) heart diseases (CHD/IHD) and (congestive) heart failure (CHF/HF) in the 8th, 9th and 10th revisions of the WHO-ICDs [25,26,27].
Table 2. Chapters and related numerical codes on coronary (ischemic) heart diseases (CHD/IHD) and (congestive) heart failure (CHF/HF) in the 8th, 9th and 10th revisions of the WHO-ICDs [25,26,27].
ICD-8ICD-9ICD-10
Coronary (Ischemic) Heart Disease (CHD/IHD)Myocardial infarction, 410Myocardial infarction, 410Angina pectoris
(4 types), I-20
Other acute and subacute forms, 411Other acute and subacute forms, 411Myocardial infarction
(6 anatomical types), I-21
Chronic, 412Old myocardial infarction, 412Subsequent infarction (4 types), I-22
Angina pectoris, 413Angina pectoris, 413Complications of myocardial infarction (8 types), I-23
Asymptomatic, 414Other, 414Other acute forms
(4 types), I-24
Chronic (9 types) including old myocardial infarction, I-25
(Congestive) Heart Failure (CHF/HF)Congestive heart failure, 427.0Congestive heart failure, 428.0Congestive heart failure, I-50.0
Left heart failure, 427.1Left heart failure, 428.1Left heart failure,
I-50.1
Unspecified, 428.9Unspecified, I-50.9
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Puddu, P.E.; Menotti, A. The Epidemiology of Isolated (Independent) Heart Failure Is Still Looking for Authors? J. Vasc. Dis. 2025, 4, 30. https://doi.org/10.3390/jvd4030030

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Puddu PE, Menotti A. The Epidemiology of Isolated (Independent) Heart Failure Is Still Looking for Authors? Journal of Vascular Diseases. 2025; 4(3):30. https://doi.org/10.3390/jvd4030030

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Puddu, Paolo Emilio, and Alessandro Menotti. 2025. "The Epidemiology of Isolated (Independent) Heart Failure Is Still Looking for Authors?" Journal of Vascular Diseases 4, no. 3: 30. https://doi.org/10.3390/jvd4030030

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Puddu, P. E., & Menotti, A. (2025). The Epidemiology of Isolated (Independent) Heart Failure Is Still Looking for Authors? Journal of Vascular Diseases, 4(3), 30. https://doi.org/10.3390/jvd4030030

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