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Screening general population for family history of sudden cardiac death unmasks high risk individuals as potential victims (pilot study)

Hamid, Lamiaa,*; Abdelfattah, Aliaa; Hussien, Khaleda; Farouk, Khaleda; Amin, Mohameda; Omar, Linab; Mokhtar, Sherif M.a

Author Information
The Egyptian Journal of Critical Care Medicine: April 2018 - Volume 6 - Issue 1 - p 9-16
doi: 10.1016/j.ejccm.2018.04.002
  • Open

Abstract

1. Introduction

Sudden Cardiac Death is defined according to ACC/AHA/ESC 2015 guidelines for management of patients with ventricular arrhythmia (VA) and the prevention of sudden cardiac death (SCD) as an unanticipated and non-traumatic deadly event taking place within one hour of the symptoms onset [1].

SCD incidence is approximately more than 3.7 million per year around the world, out of which 250,000–300,000 are in USA [2,3]. The annual incidence of SCD in USA and Europe is estimated to be from 50 to 100 per 100,000 in the general population [4–6], and reported to range from 37 to 43 per 100,000 in Asia [7–10]. Our study is an attempt to address the population of SCD and the associated risk factors of coronary artery disease in Egypt, an important large African nation.

SCD is what up to half of cardiac deaths are attributed to [4,38–40]. Although SCD mostly occur in CAD settings [11–13], CAD are not previously recognized in more than half of SCD cases and sudden cardiac arrest is the first symptom

In the general population, the risk factors for sudden death are generally the same as the major risk factors for the development of CAD [11].

The main reasons behind the ambiguity of SCD annual incidence is not only because most of studies are retrospective and/or dependent on death certificates data, but because of the discrepancies in case definitions and determination of SCD also [14].

Regardless the presence of many co-morbidities, SCD is listed to be the primary death cause in death certificates in many cases [18]. Death certificates are found to overestimate the incidence of SCD yet it does not account SCA survivors [15–17].

Like death certificate data, other sources of retrospective case ascertainment such as vital statistics and census data also misclassify and can overestimate SCD. The prospective community-based studies, used data from first-responders, which results in the inherent exclusion of un-witnessed SCA and/or SCD [18].

As CAD has been found to cluster in families [19], individuals with positive family history of SCD are more liable to SCA, besides the main documented risk factors of CAD and primary cardiac arrest is found to have genetic determinants [19]. The hypothesis developed is whether the aggregation of PCA is due to the familial aggregation of these risk factors or to genetic and/or environmental determinants that other family members share. In several studies, a family history of MI or CHD was shown to be a strong predictor of CHD, even after adjustment for other risk factors [19], yet this issue has remained controversial [20].

As there are no large scale Egyptian surveys estimating the prevalence of cardiac disease and associated clinical symptoms or the incidence of SCD in a non-selected (e.g. non-athlete) population, the purpose of this report was to assess the relation between family history of SCD and the presence of CAD or coronary risk factors as first degree relatives of SCD victims.

2. Aim of the study

This pilot study is aiming to estimate the magnitude of SCD problem in Egypt and searching for potential victims. A fast-response questionnaire screening CAD risk factors and cardiac problems as indicators for SCD was developed, it had to be a short questionnaire in order to receive a great adherence and that could simultaneously provide precise information, in a way that a triage could be performed in the general adult population to detect adults at risk of SCD and with an indication for further evaluation and possible need of:

  • Medical Treatment
  • Electro-physiologic (EP) Study and/or Percutaneous Ablation
  • Implantable Cardiovertor Defibrillator (ICD)
  • Pacemaker implantation
  • Other Types Of Specialized Cardiac Interventions

3. Population

This is a prospective community based study conducted throughout the year 2015 (pilot study) on 8786 candidates. Of them, 7916 completed the questionnaires, with a response rate of 90% (total completed/total surveyed). Ages ranged from 4 years to 85 years with a median of 18, males constituted 34.4% of the total vs. (65.6%) females. Out of total those below 20 years constituted 77.6% (6497), those from 20 years to 40 years constituted 10.4% (868), and those above 40 years constituted 12.2% (1015) while males constituted 34.4% (3845) of the total vs. 65.6% (5936) females.

3.1. Places of sample collection

  • University departments (Cairo University employees): 839
  • Student associations and other places that gather university students (Cairo University): 6744
  • Sports venues (shooting club): 534.
  • Convoys to different geographic locations: 669. (El Saf, El Moneeb, El Marg, Ain el Syra, Shabramant)

Information collection in these places was performed under the permission of proper authorities.

4. Methodology

Data were collected by means of 1) a questionnaire only protocol (random samples were collected among university students, social clubs and governmental employees) and 2) a questionnaire plus clinical examination, ECG and laboratory investigations during medical convoys (random samples were collected from rural areas). Data were coded and verified according to presence and absence of coronary artery disease risk factors, ischemic heart disease and other risk factors shown in Fig. 1.

Fig. 1.
Fig. 1.:
Questionnaire.

SCD Risk Factors studied/included:

  • o Family History of SCD
  • o DM: on anti-diabetic treatment
  • o Family history of DM
  • o Hypertension: Blood pressure above 140/90 mmHg
  • o Family history of Hypertension
  • o Hypercholesterolemia: Lipid lowering drugs
  • o CAD: Coronary Artery Disease
  • o Family history of CAD
  • o CHF: Congestive Heart Failure
  • o ICD: Implantable Cardiovertor Defibrillator
  • o RHD: Rheumatic Heart Disease
  • o CHB: Complete Heart Block
  • o HOCM: Hypertrophic Obstructive Cardiomyopathy
  • o Obesity:
  • o Smoking

Positive family history of SCD was chosen empirically as a potential marker for vulnerability of SCD. Data was analyzed using SPSS22 –statistical package for social science. We could elicit the number of subjects who completed the questionnaire according to each risk factor.

5. Statistical methods

  • Data were coded, verified,
  • All quantitative variables were expressed as mean and SD, qualitative variables were expressed as percentages in frequency tables
  • Chi-square test has been used to test association between qualitative variables.
  • P value less 0.05 considered significant.
  • Data was analyzed using SPSS22 –statistical package for social science.
  • Odds ratio (OR) has been calculated with 95% confidence interval (CI)

6. Results

Data were looked up and analyzed from four different aspects to estimate the following

  1. The prevalence of positive family history of SCD among general population of 8786 candidates.
  2. The prevalence of positive family history for variable risk factors for CAD, the actual presence of CAD risk factors and structural heart diseases within the entire group of 8786 representing the general population.
  3. The prevalence of positive family history for variable risk factors for CAD, the actual presence of CAD risk factors and structural heart disease within the subgroup of 293 with positive family history of SCD representing potential victims.
  4. Comparing the group with positive family history of SCD with group with negative family history of SCD with particular emphasis on the family history and actual presence of risk factors, life style, and actual presence of IHD.

6.1. Characteristics of general population data (8786)

Among 8789 candidates (general population) 3.5% had positive family history of SCD 13.7% had positive family history of diabetes mellitus, 12.7% had positive family history of consanguinity, 12.2% had positive family history of hypertension, 5.1% had positive family history of CAD, 7.6% had history of syncope, 7.3% were hypertensive, 4.4% were smokers, 4.4% were diabetic, 4.5% had high cholesterol level, 1.6% were obese and 1% had ischemic heart disease (See Fig. 3).

Fig. 3.
Fig. 3.:
Individual risk factors among total population.

6.2. Characteristics of group positive family history of SCD Data (293)

Out of the 8786 questioned subjects, 293 had positive family history of SCD (3.5%), see Fig. 2.

Fig. 2.
Fig. 2.:
Family history of risk factors among total population.

Family history of sudden cardiac death was chosen as a potential marker of vulnerability to SCD and the main step in the screening process to detect potential victims. Males (104) constituted 35.5%, and females (189) constituted 64.5%. Those below 20 years (69) constituted 24.2%, those from 20 years to 40 years (96) constituted 33.7%, and those above 40 years (120) constituted 42.1%. Sex and age Distribution are shown in Figs. 4 and 5 respectively (See Table 1).

Fig. 4.
Fig. 4.:
Sex Distribution of 293 candidates with positive family history SCD.
Fig. 5.
Fig. 5.:
Age Distribution among 293 with Positive Family history of SCD.
Table 1
Table 1:
Location distribution among surveyed groups with positive family history of sudden death.

Among 293 candidates (positive family history of SCD) 55.5% had positive family history of diabetes mellitus, 22.3% had positive family history of consanguinity, 48% had positive family history of hypertension, 34.4% had positive family history of CAD, 33.4% had history of syncope, 32.6% were hypertensive, 17.1% were smokers, 18.4% were diabetic, 26.3% had high cholesterol level, 12.3% were obese and 6% had ischemic heart disease (See Figs. 6 and 7).

Fig. 6.
Fig. 6.:
Family history of risk factors among positive family history of SCD group.
Fig. 7.
Fig. 7.:
Individual risk factors among positive family history of SCD group.

7. Comparison between group1 (with positive family history of SCD) and group 2 (with negative family history of SCD) according to different risk factors

7.1. Role of family history of different risk factors

There was significant association between family history of SCD and family history of DM, family history of consanguinity, family history of CAD and family history of HTN:

There was a significant association between positive family history of SCD and the presence of family history of Diabetes mellitus (55.5% VS 12.4%) with P value of 0.0001. Those who had positive family history of diabetes mellitus were 8.7 times more frequently associated with positive family history of SCD with odds ratio of 8.7 and confidence interval of 6.7–11.4 (See Table 2).

Table 2
Table 2:
Family history risk factors among total population, positive family history of SCD group and negative family history of SCD group.

There was a significant association between positive family history of SCD and the presence of family history of consanguinity (22.5% VS 12.4%) with P value of 0.0001.Those who had positive family history of consanguinity were 2 times more frequently associated with positive family history of SCD with odds ratio of 2.04 and confidence interval of 1.4–2.8.

There was a significant association between positive family history of SCD and the presence of family history of CAD (34.4% VS 4.2%) with P value of 0.0001.Those who had positive family history of CAD were 12 times more frequently associated with positive family history of SCD with odds ratio of 11.9 and confidence interval of 8.9–16.1.

There was a significant association between positive family history of SCD and the presence of family history of HTN (48% VS11.2%) with P value of 0.0001.Those who had positive family history of HTN were 7 times more frequently associated with positive family history of SCD with odds ratio of 7.3 and confidence interval of 5.7–9.6.

7.2. Role of life style

There was significant association between family history of SCD and Obesity and syncope

Out of the total population 1.6% (127) were obese, while 12.3% [29] were obese among the group with positive family history of SCD and only 1.3% (98) were obese in the group with negative family history of SCD.

There was a significant association between positive family history of SCD and the presence of obesity (12.3% VS 1.3%) with P value of 0.0001. Those who were obese were 11 times more frequently associated with positive family history of SCD with odds ratio of 10.96 and confidence interval of 7.08–16.9.

Subjects who has history of syncope were 7.5% (600) out of the total population, 33.9% (80) out of the group of subjects with positive family history of SCD and only 6.7% (520) out of the group with negative family history of SCD (See Table 3).

Table 3
Table 3:
Actual presence of CAD risk factors among total population, positive family history of SCD group and negative family history of SCD group.

There was a significant association between positive family history of SCD and the presence of syncope (33.9% VS 6.7%) with P value of 0.0001.Those who had syncope were 7 times more frequently associated with positive family history of SCD with odds ratio of 7.1 and confidence interval of 5.3–9.4.

7.3. Role of actual presence of CAD risk factors

There was significant association between family history of SCD and DM, hypercholesterolemia and HTN

There was a significant association between positive family history of SCD and the presence of DM (18.4% VS 3.8%) with P value of 0.0001.Those who had DM were 6 times more frequently associated with positive family history of SCD with odds ratio of 5.6 and confidence interval of 4.1–7.7.

There was a significant association between positive family history of SCD and the presence of hypercholesterolemia (26.3% VS 3.8%) with P value of 0.0001. Those who had hyper-cholesterolemia were 9 times more frequently associated with positive family history of SCD with odds ratio of 9.1 and confidence interval of 6.6–12.4.

There was a significant association between positive family history of SCD and the presence of hypertension (32.6% VS 6.4%) with P value of 0.0001.Those who had hypertension were 7 times more frequently associated with positive family history of SCD with odds ratio of 7.08 and confidence interval of 5.4–9.2.

7.4. Role of actual presence of ischemic heart disease

7.4.1. IHD patients

There was a significant association between positive family history of SCD and actual presence for IHD (6% VS 0.9%) with P value of 0.0001, those who had IHD were 7.13 times more frequently associated with positive family history of SCD with odds ratio of 7.13 and confidence interval of 3.9–12.8.

8. Discussion

8.1. Family screening in search for potential victims of SCD

Sudden cardiac death (SCD) remains one of the most prevalent modes of death in industrialized countries. Sudden death in the adult population most often occurs in the setting of coronary artery disease [11–13]. In more than half of such cases, coronary heart disease has not previously been recognized clinically, and SCD occurs as its first symptom (Davies 1992). In a large fraction of cases, SCD is caused by primary ventricular fibrillation (VF), ie. VF in the setting of acute ischemia and in the absence of heart failure.1

Risk factors for CHD development and risk factors are mostly the same in general population [21–29].

Screening efforts for potential victims of SCD in a huge country like Egypt is of course a major undertaking. Even in a city like Cairo (16 millions) it would be impossible to come up but with only approximate figures. Difficulties are numerous particularly in relation to the historical, traditional, cultural, and religious backgrounds amongst Egyptians.

There are several factors limiting ideal Data collection in EGYPT

The first difficulty most individuals are uncooperative to share information about their lives, especially when in cases of death. SCD victims' families are unwilling to share information with non-medical employees about reasons and conditions of death [30].

The second difficulty: is the time-consuming required to explain the importance of signing a consent and excluding inherited disorder as the SCD cause

The third difficulty: culture and religious backgrounds are an obstacle to perform autopsies and

The fourth difficulty: is the missing medical history data

Our Efforts were therefore concentrated on indirect indicators namely; risk factors that would predispose to SCD (they are in fact risk factors predisposing for CAD, the most common underlying mechanisms of SCD in adults) and second is the presence of positive family history of SCD amongst screened population.

Screening of the general population has been conducted through 8 convoys comprising wide age range (from below 4 to 85 years), both sexes (67.6% F, 32.4 M) and different socio-economic classes.

The presence of positive family history of SCD in our study was selected as a marker for vulnerability of family members to cardiac sudden death.

Compared to those with no family history of SCD, those with positive family history of SCD were 8.7 times more associated with family history of DM, two times more associated with family history of consanguinity, 12 times more associated with family history of CAD, 7 times more associated with family history of HTN, Two times more associated with smoking, 11 times more associated with obesity, 7 times more associated with syncope.

Our findings are in agreement with many retrospective studies [31,32], prospective studies [33–35], and angiography studies [36,37] which have all clearly demonstrated a familial aggregation for CHD.

The question of whether aggregation of primary cardiac arrest is caused by risk factors – CHD risk factors which have tendency to cluster in families- or due to genetic and/or environmental factors that are shared between family members and exerts its effects.

Indifferent words, people that are more prone to myocardial infarction or PCA will be more in risk to PCA by smoking and having hyperlipidemia that others without such history.

The common risk factors associated with CHD are considered to be prognostic to SCD such as age, systolic blood pressure, serum cholesterol level, vital capacity, cigarette smoking, obesity, DM, heart rate, and ECG abnormalities.

8.2. Diabetes, CAD, and risk of SCD

“Common soil” hypothesis suggests that diabetes and cardiovascular disease come from the same soil, in other words have the same genetic and/or environmental factors along with the fact that among patients with type 2 diabetes, cardiovascular diseases are the most common cause of morbidity and mortality [41–44].

Diabetes has been considered to be SCD risk factor, but not for nonfatal myocardial infarction [45]. Mortality and death rates of diabetics are compounded, as many diabetics do not know of a metabolic syndrome they suffer from. “ticking clock” hypothesis assumes that risk of cardiovascular disease is elevated before onset of clinical diabetes [46].

9. Summary

The findings of the present study, that diabetes, hypertension, and smoking are significant risk factors for family history of sudden cardiac death, are consistent with the findings of numerous other epidemiological investigations

Our findings are in agreement with many retrospective studies [17–19] prospective studies [20–24] and angiography studies [25,26] which have all clearly demonstrated a familial aggregation for CHD.

In this population-based case-control study, a family history of myocardial infarction or SCD was, after correction for all common risk factors, positively associated with the risk of SCD

9.1. This study has shown a number of significant findings

A family history of recurrent premature SCD or inheritable heart disease represents a ‘red flag’ that makes familial evaluation strongly recommended.

Addressing the problem of sudden cardiac death generally faces on two issues; the first concerns the magnitude of the problem and the second centers at preventing the disaster by searching for potential victims, and subjecting them to diagnostic and interventional strategies.

In this study we faced the challenge by choosing one single parameter i.e. positive family history of sudden cardiac death.

Choosing the latter parameter was based on the available literature pointing to the role of positive family history in identifying potential victims.

  • Out of 8786, 293 candidates had positive family history of SCD which represents 3.5%, 127 candidates were obese which represents (1.6%), 1006 candidates had positive consanguinity which represents (12.7%), 365 candidates had Diabetes Mellitus which represents (4.4%), 356 candidates had high cholesterol which represents (4.5%), 402 candidates had positive family history of CAD which represents (5.1%), 606 candidates had history of syncope which represents (7.6%)604 candidates were hypertensive which represents (7.3%), 966 candidates had family history of hypertension which represents (12.2%) and 1097 candidates had family history of DM which represents (13.8%)
  • Out of 293 with positive family history of SCD, 29 were obese (12.3,52 had positive consanguinity (22.3%), 54 had Diabetes Mellitus (18.4%), 62 had high cholesterol (18.4%), 78 had positive family history of CAD (22.3%), 80 had syncope (33.4%), 93 were hypertensive (32.6%), 109 had positive family history of hypertension (48%), 131 had positive family history of diabetes mellitus (55.5%)

10. Conclusion

The present work emphasizes the role of positive family history of CAD, obesity, DM, and consanguinity in pointing to the potential victims in family members of with positive family history of SCD.

Compared to those with no family history of SCD, those with positive family history of SCD were 8.7 times more associated with family history of DM, two times more associated with family history of consanguinity, 12 times more associated with family history of CAD, 7 times more associated with family history of HTN, Two times more associated with smoking, 11 times more associated with obesity, 7 times more associated with syncope.

It underscores the importance of searching for positive family history of sudden cardiac death as a warning marker a red flag that makes familial evaluation strongly recommended.

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