Is Parental Longevity Associated With the Cardiovascular Risk and the Successful Aging of Their Offspring? Results From the Multinational MEDIS Study

Abstract

The aim of the present study was to evaluate the role of parental longevity and parental cardiovascular disease (CVD) history in CVD risk and successful aging of a random sample of older adults living in the Mediterranean basin and who participated in the MEDiterranean Islands (MEDIS) study. During 2005 to 2011, 2663 elders were voluntarily enrolled. A multidimensional successful aging index consisting of 10 components was used. Paternal and maternal longevity was defined as those older participants of whom both parents lived above the age of 90. The burden of CVD-related factors (CVD-RFs) was calculated as the total score of 4 major CVD-RFs (range 0-4). After adjustment, parental longevity was inversely associated with the burden of CVD-RFs (P = .04). Moreover, parental longevity was positively associated with the older adults’ successful aging score (β-coefficient [95% confidence interval]: .38 [0.06-0.71]). Parent’s long living was revealed as an important factor for successful aging and for reduced CVD risk, suggesting that further research is needed in the genetic predisposition of longevity.

Keywords

parental longevity successful aging cardiovascular disease older adults Mediterranean basin

Introduction

The principles of longevity and healthy and successful aging remain among the major challenges of public health.¹ Until now, many studies have proposed that longevity follows familial pathways² and could be inherited. According to researchers, a complex phenotype is accompanying the “long livers” and more particularly the centenarians, as a result of their improved capacity to physiologically adapt throughout the various life stages.^3,4 Specifically, long-liver groups, such as the centenarians, are characterized by delayed onset of cardiovascular disease (CVD), certain cancers, dementia, and cognitive and functional impairment.^5

–9 Following the healthy status of their long-living parents, their offspring are experiencing a similar long-living pathway. Previous findings indicate that long livers’ offspring are having lower risk for CVD events and CVD-related factors (CVD-RFs; ie, hypertension, diabetes mellitus, etc)^10,11 and thus have a significant survival advantage.^12
–14

In parallel, it is well known that cardiovascular health encompasses both familial (genetic) components and environmental factors.^15
–17 Various studies have indicated the role of maternal and paternal CVD history on the CVD health status of their offspring.^16,17 Previous studies suggest that parental long living is beneficially related to their offspring’s health status; however, the adjustment for parental clinical history is sparse.¹⁸ Clearly, the process of longevity is quite complex and is associated with a variety of factors, not only with physical health. Successful aging is a concept that is considered as a low probability of disease and disability, high cognitive and physical capacity, active participation throughout various social activities, and represents the aforementioned complexity in the longevity process.^19,20 Until now, to the best of our knowledge, there is a lack of epidemiological evidence on the role of parental longevity and CVD history in successful aging.

Given the complexity of the human longevity and aging pathway, together with the lack of data among Mediterranean populations, the aim of the present study was to evaluate the role of parental longevity and parental CVD history in CVD risk and successful aging of a random sample of older adults living in the Mediterranean basin and who participated in the MEDiterranean ISlands (MEDIS) study. The MEDIS study sample encompasses 2 of the already reported high life-expectancy areas in the world (ie, the islands of Ikaria and Sardinia). In addition, the selected older Mediterranean population has rarely been studied in the last 4 decades, a fact that makes this survey of major importance, as it included 2 of the islands (ie, Corfu and Crete) where Keys and his colleagues from the Seven Countries Study first observed the basic components of longevity.²¹

Methods

The MEDIS Study Sample

During 2005 to 2011, a population-based, multinational, convenience sampling was performed to voluntarily enroll older people from 21 Mediterranean islands (the target sample size was 300 people from the Republic of Cyprus, 250 from Malta, and 150 from each of the other islands/areas): Republic of Cyprus (n = 300), Malta (n = 250), Sardinia (n = 60), Sicily (n = 50), Mallorca and Menorca (n = 111), and the Greek islands of Lesvos (n = 142), Samothrace (n = 100), Cephalonia (n = 115), Crete (n = 131), Corfu (n = 149), Limnos (n = 150), Ikaria (n = 76), Syros (n = 151), Naxos (n = 145), Zakynthos (n = 103), Salamina (n = 147), Kassos (n = 52), Rhodes and Karpathos (n = 149), Tinos (n = 129), as well as from the rural region of Mani (n = 153; a southern Greek peninsula). According to the study protocol, individuals were not eligible for inclusion if they resided in assisted-living centers, had a clinical history of CVD or cancer, or had lived away from the island or region for a considerable period of time during their lives (ie, >5 years); these exclusion criteria were applied because the study aimed to assess lifestyle habits that were not subject to modifications due to existing chronic health conditions or by environmental factors, other than living milieu. A group of health scientists (physicians, dietitians, nutritionists, and nurses) with experience in field investigation collected the required information using a quantitative questionnaire and standard procedures.

The study followed the ethical considerations provided by the World Medical Association (52nd WMA General Assembly, Edinburgh, Scotland, October 2000). The Institutional Ethics Board of Harokopio University approved the design and procedures of the study (reference no. 16/19-12-2006). Participants were informed about the aims and procedures of the study and gave their consent prior to being interviewed.

Evaluation of Clinical Characteristics

All of the measurements carried out in the different study centers were standardized, and the questionnaires used were translated in all cohort languages following the World Health Organization translation guidelines for tools’ assessment.²² Weight, height, and waist circumference were measured using a standard protocol; body mass index (BMI) was calculated as the ratio of weight by height squared (kg/m²). Overweight was defined as BMI between 25 and 29.9 kg/m², and obesity was defined as BMI >29.9 kg/m². Diabetes mellitus (type 2) was determined by fasting plasma glucose tests and was analyzed in accordance with the American Diabetes Association diagnostic criteria (glycated hemoglobin A1C ≥6.5% or fasting blood glucose levels greater than 125 mg/dL or 2-hour plasma glucose >200 mg/dL during an oral glucose tolerance test or a random plasma glucose >200 mg/dL or by a prior diagnosis of diabetes). Participants who had blood pressure levels ≥140/90 mm Hg or used antihypertensive medications were classified as hypertensive. Fasting blood lipid levels (high-density lipoprotein cholesterol and low-density lipoprotein cholesterol and triglycerides) were also recorded, and hypercholesterolemia was defined as total serum cholesterol levels >200 mg/dL or the use of lipid-lowering agents according to the National Cholesterol Education Program-Adult Treatment Panel III guidelines.²³

Parental longevity was defined as those older participants of whom both parents were long livers, beyond the age of 90. Moreover, maternal and paternal history of diabetes type II, hypertension, and hypercholesterolemia was recorded. No information on maternal and paternal history of obesity was collected. A cumulative paternal and maternal “CVD history index” was developed, summing the 3 health-specific, binary variables mentioned before (a score of 1 was given for each additional related factor: hypertension, hypercholesterolemia, and diabetes type II, so theoretical range was 0-3). Further classification was applied. Specifically, those with score 0 were classified with no maternal and paternal CVD history, whereas those with score 1 to 3 were grouped as having maternal and paternal CVD history.

Evaluation of Dietary Habits, Sociodemographic, and Other Lifestyle Characteristics of the Participants

Dietary habits were assessed through a semiquantitative, validated, and reproducible food-frequency questionnaire.²⁴ Furthermore, consumption of various alcoholic beverages (ie, wine, beer, whiskey, vodka, and the traditional ouzo, tsipouro, and retsina) was measured in terms of wineglasses per day, adjusted for ethanol intake (eg, one 100 mL glass of wine was considered to have 12% ethanol), and classified for the present analyses into 0 for no alcohol consumption and 1 for alcohol consumption of at least 1 glass/wk. To evaluate the level of adherence to the Mediterranean diet, the MedDietScore (theoretical range 0-55) was used.²⁵

Basic sociodemographic characteristics, such as age, gender, years of schooling, financial status, and lifestyle characteristics, such as smoking habits and physical activity status, were recorded. Regarding financial status, the participants were asked to report their mean income during the previous 3 years using a 4-point scale (low, inadequate to cover daily expenses = 1; medium, trying hard to cover daily expenses = 2; good, adequate to cover daily expenses = 3; and very good, very adequate to cover daily expenses = 4). This scale was decided upon because of the variety of the populations studied, as well as the common difficulty of accessing exact financial data. The participants who were in the upper category were classified as participants with high financial status, whereas all the others were classified as low and medium financial status (high vs low–medium financial status). Current smokers were defined as smokers at the time of the interview. Former smokers were defined as those who had previously smoked but had not done so for a year or more. The remaining participants were defined as occasional or noncurrent smokers. Physical activity was evaluated in metabolic equivalent of task (MET) minutes per week, using the shortened and validated Greek version of the self-reported International Physical Activity Questionnaire²⁶ translated in all the cohort’s languages. Individuals who reported at least 3 MET minutes per week were classified as minimally active or “health-enhancing physical activity (HEPA) active.” Furthermore, the weekly frequency of physical activity was recorded. Symptoms of depression during the previous month were assessed using the validated Greek version (also translated in all the cohort’s languages) of the shortened, self-report Geriatric Depression Scale (GDS; range 0-20).²⁷ Moreover, in order to evaluate the older adults’ social participation, the weekly frequency of their social activities with their family and their friends as well as their yearly frequency of excursions were recorded. Further details about the MEDIS study protocol may be found elsewhere.²⁸

Evaluated Outcomes

Following the multidimensional approach to successful aging already reported by several experts²⁹ and the MEDIS study group,²⁰ 10 components (ie, education, financial status, physical activity, BMI, GDS score, participation in social activities with friends, with family, yearly excursions, CVD-RFs score, and MedDietScore) were incorporated for the measurement of successful aging. The composed successful aging index was represented as the cumulative score of the 10 components (theoretical range 0-10); specifically, individual ratings (from 0 to 1) in each of the 10 components were assigned, according to their positive or negative (ie reverse scoring) influence on successful aging, according to the current literature.²⁰

Moreover, a cumulative score indicating the overall burden of CVD-RFs of the older participants was calculated (a score of 1 was given for each additional risk factor: hypertension, hypercholesterolemia, diabetes, and obesity, so the theoretical range was 0-4).

Statistical Analysis

Continuous variables are presented as mean ± standard deviation and categorical variables as frequencies. Comparisons of continuous variables between groups of study were performed using the independent samples t test (for the normally distributed variables) or the Mann-Whitney U test and the Kruskal-Wallis test (for the skewed variables). Associations between categorical variables were tested using the χ² test. Nested multiple logistic regression models were applied to estimate, for an offspring, the odds of having overall CVD-RF “morbidity index” (0-2 related factors vs 3-4 related factors), taking into account other participants’ characteristics (ie, age, sex, education and financial status, living alone, former smoking habits, physical activity, adherence to the Mediterranean diet, alcohol consumption, parental longevity, and maternal and paternal CVD history). Nested linear regression models were also applied in order to further evaluate the association between various factors (ie, sociodemographic, bioclinical, lifestyle factors, parental longevity, and maternal and paternal CVD history) that were potentially associated with the odds of having overall 3 to 4 CVD factors and the level of successful aging. Colinearity was tested using the variance inflation factor criterion (values >4 suggested colinearity between independent variables, and one of them was excluded from the model). The assumption of homoscedasticity was tested by plotting the scatterplot of standardized residuals over the predicted score values. Results from linear regression models are presented as β-coefficients and their 95% confidence interval (CI). No correction for multiple comparisons testing was performed, because the tested hypotheses were independent. All reported P values were based on 2-sided tests. SPSS software (version 20) was used for all calculations (IBM Statistics, Greece).

Results

Among the MEDIS sample, paternal longevity (father lived ≥90 years) was 9% and maternal longevity (mother lived ≥90 years) was 12%. When the 7 geographical areas of the participants were taken into account (West Mediterranean, Ionian, Aegean, Saronikos islands, Crete island, Mani, and Cyprus Republic), the inhabitants of the Republic of Cyprus had the highest prevalence of paternal and maternal longevity (ie, 19% and 22%), whereas the participants living in the islands of West Mediterranean (Malta, Sardinia, Sicily, and Balearic islands) had the lowest paternal longevity (ie, 4%) and Saronikos islands had the lowest maternal longevity (ie, 5%; P < .001). Parental longevity regarding the 7 geographical areas is presented in Table 1. When rural and urban areas were compared, a significant difference emerged with regard to the proportion of older adults exhibiting paternal longevity (both mother and father lived ≥ age of 90; 6% vs 5%, P = .008). Moreover, older adults living in urban areas had a higher burden of parental CVD history as opposed to those living in rural areas (ie, 52% vs 37%, P < .001).

Table 1.

Parental Longevity (Both Long-Lived Parents) Among Different Geographical Areas of the MEDIS Study.

Geographical Areas	Parental Longevity
Aegean Islands, %^a	4
Island of Crete, %	2
Ionian Islands, %^b	4
Republic of Cyprus, %	7
West Mediterranean Islands, %^c	2
Saronikos Islands, %^d	2
South Peloponnesus, %^e	7

Abbreviation: MEDIS, MEDiterranean Islands.

^aAegean area includes the islands of Lesvos, Samothrace, Limnos, Ikaria, Syros, Naxos, Kassos, Rhodes and Karpathos, and Tinos.

^bIonian area includes the islands of Cephalonia, Corfu, and Zakynthos.

^cWest Mediterranean area includes the islands of Malta, Sardinia, Sicily, Mallorca, and Menorca.

^dSaronikos area includes the island of Salamina.

^eSouth Peloponnesus area includes the rural area of Mani.

Analytical demographic, behavioral, clinical, and lifestyle characteristics of the sample by parental (ie, maternal, paternal, and parental) CVD history are summarized in Table 2. Compared with older adults with no parental CVD history, those with parental CVD history had a higher prevalence of hypertension (P < .001), diabetes type II (P < .001), hypercholesterolemia (P < .001), and a higher burden of CVD-RF (P < .001) and were classified within high financial status (P < .002). No consistent differences were observed, however, between the groups with regard to their BMI level, smoking habits, living alone, alcohol consumption, adherence to the Mediterranean diet, physical activity, and successful aging.

Table 2.

Demographic, Behavioral, and Lifestyle Characteristics of the Multinational MEDIS Sample by Parental CVD History.

	No Maternal CVD History (n = 905)	Maternal CVD History (n = 305)	P	No Paternal CVD History (n = 803)	Paternal CVD History (n = 407)	P	No Parental CVD History (n = 654)	Parental CVD History (n = 553)	P
Age	74.5 ± 7.4	72.9 ± 6.9	.001	74.7 ± 7.4	72.9 ± 6.9	<.001	75.2 ± 7.5	72.8 ± 6.9	<.001
Sex (male, %)	48	49	.70	51	41	.001	52	43	.001
BMI, kg/m²	29.0 ± 11.0	28.7 ± 4.6	.72	28.8 ± 11.4	29.2 ± 4.8	.53	28.9 ± 12	28.9 ± 5.0	.99
Education (years of schooling)	6.4 ± 4.0	7.2 ± 4.1	.10	6.5 ± 4.2	6.8 ± 3.9	.35	6.4 ± 4.2	6.8 ± 3.9	.18
High financial status, %	15	17	.43	11	25	<.001	11	20	.002
Living alone, %	26	22	.19	24	28	.14	24	28	.44
Former smoking habits, %	37	35	.80	38	33	.22	40	32	.06
Physical activity, %	65	47	.50	48	80	.16	49	72	.30
MedDietScore (0-55)	33.4 ± 4.6	32.9 ± 4.6	.16	33.5 ± 4.5	33.0 ± 4.7	.21	33.5 ± 4.7	33.1 ± 4.7	.25
Alcohol consumption, %	47	50	.28	47	49	.51	45	50	.09
Hypertension, %	59	70	.001	55	74	<.001	54	71	<.001
Diabetes mellitus, %	22	35	<.001	22	31	.001	20	32	<.001
Hypercholesterolemia, %	49	64	<.001	45	68	<.001	42	65	<.001
CVD risk score (0-4)	1.6 ± 1.1	2.0 ± 1.1	<.001	1.5 ± 1.1	2.1 ± 1.1	<.001	1.5 ± 1.1	2.0 ± 1.1	<.001
Successful aging index (0-10)	2.5 ± 1.3	2.6 ± 1.4	.80	2.5 ± 1.3	2.7 ± 1.4	.05	2.5 ± 1.3	2.6 ± 1.4	.75

Abbreviations: BMI, body mass index; CVD, cardiovascular disease; MEDIS, MEDiterranean Islands.

Age, gender, education and high financial status, living alone, physical activity, smoking habits, alcohol consumption, and adherence to the Mediterranean diet, adjusted logistic regression analysis, showed that older adults with parental longevity were 0.4 times less likely to have an increased burden of CVD-RF, as opposed to those with no parental longevity (95% CI: 0.16-0.98; model 1). The latter model was further adjusted for maternal and paternal CVD history. When these factors were taken into account, parental longevity was not associated any more with the burden of CVD-RFs among the older adults (model 2). Moreover, in this model, the habit of consuming alcohol appears to offer some protection against the accumulation of factors associated with CVD (Table 3).

Table 3.

Results From Nested Multiple Logistic Regression Models Performed to Evaluate the Association of Various Sociodemographic, Bioclinical, Lifestyle Characteristics, Parental Longevity, and CVD History of the Multinational MEDIS Study Participants in Relation to the Overall CVD-RF “Morbidity Index” + (0-2 Related Factors vs 3-4 Related Factors).

	Model 1		Model 2
	OR	95% CI	OR	95% CI
Paternal longevity (yes vs no)	0.40^a	0.16-0.98	0.88	0.21 to 3.64
Age (per 1 year)	0.96^b	0.94-0.98	0.99	0.96 to 1.03
Sex (men vs women)	0.52^b	0.33-0.82	0.53^a	0.28 to 1.00
Education status (years of school)	0.93^b	0.88-0.98	0.95	0.88 to 1.03
High financial status (yes vs no)	0.83	0.52-1.32	0.53	0.24 to 1.16
Living alone (yes vs no)	0.81	0.56-1.16	0.74	0.41 to 1.23
Physical activity (yes vs no)	1.05	0.74-1.49	0.92	0.55 to 1.54
MedDietScore (change per unit)	1.01	0.97-1.06	1.03	0.96 to 1.11
Former smoking (yes vs no)	1.12^a	1.05-1.20	1.85	0.93 to 3.67
Alcohol consumption (yes vs no)	0.66^a	0.46-0.95	0.55^a	0.32 to 0.93
Maternal CVD history (yes vs no)	-	-	0.79	0.45 to 1.39
Paternal CVD history (yes vs no)	-	-	1.98^a	1.19 to 3.29

Abbreviations: CI, confidence interval; CVD, cardiovascular disease; CVD-RF “morbidity index,” score 1 was given for each additional risk factor: hypertension, hypercholesterolemia, diabetes, and obesity, theoretical range (0-4); OR, odds ratio.

^a P < .05.

^b P < .01.

The above mediating association among parental longevity and parental CVD history was further tested throughout the wider concept of successful aging. Specifically, after adjusting for age, gender, smoking habits, and alcohol consumption, parental longevity was positively associated with the successful aging score (β-coefficient [95% CI]: .38 [0.06-0.71]) of islanders (model 1). However, when paternal and maternal CVD history was taken into account, the association of parental longevity with the older adults’ successful aging score disappeared (model 2; Table 4).

Table 4.

Results From Nested Linear Regression Models Performed to Evaluate the Association of Sociodemographic, Lifestyle Characteristics, Parental Longevity, and CVD History, Which Were Found to be Previously Associated With Participants’ CVD-Related Factors, in Relation to the Level of Successful Aging.

	Model 1		Model 2
	β-coefficient	95% CI	β-coefficient	95% CI
Parental longevity (yes vs no)	.38^a	0.06 to 0.71	.58	−0.10 to 1.26
Age (per 1 year)	−.08	−0.02 to −0.002	−.01	−0.03 to 0.008
Sex (males vs females)	.53^b	0.34 to 0.71	.72^b	0.40 to 1.04
Living alone (yes vs no)	−.17^a	−0.33 to −0.008	−.19	−0.47 to 0.08
Former smoking habits (yes vs no)	.13	−0.06 to 0.32	.21	−0.10 to 0.53
Alcohol consumption (yes vs no)	.49^b	0.34 to 0.64	.60^b	0.35 to 0.86
Maternal CVD history (yes vs no)	-	-	−.04	−0.31 to 0.21
Paternal CVD history (yes vs no)	-	-	.25	−0.02 to 0.54

Abbreviations: CI, confidence interval; CVD, cardiovascular disease.

^a P < .05.

^b P < .001.

Discussion

The present study revealed that parental longevity was inversely associated with their offspring’s burden of CVD risk, irrespective of age, gender, education and high financial status, living alone, physical activity, smoking habits, alcohol consumption, and adherence to the Mediterranean diet. In addition, a positive association between parental longevity and the older adult’s successful aging level was reported. However, the latter findings became nonsignificant when paternal and maternal CVD-RF history was considered in the analysis. The confounding role of paternal and maternal CVD history on the relationship between parental longevity and older adult’s burden of CVD-RF and successful aging status could imply that it is not only the possible inherited factor of longevity that promotes successful aging and CVD health but also the burden of parental CVD-RFs. All of the aforementioned relationships, especially among elderly Mediterranean populations, have rarely been studied.

Despite the lack of previous findings regarding parental longevity and CVD health and successful aging among Mediterranean populations, a number of studies have previously reported that long livers’ offspring also enjoy a “healthy” longer life. More specifically, the offspring of long livers have lower risk for CVD, as well as various CVD-RFs (ie, hypertension, diabetes mellitus, etc).^10,11 Within our data analysis, a number of components as well as parental longevity and their offspring’s burden of CVD-RFs were explored to reveal the positive role of parental longevity on their offspring’s CVD health (model 1). According to several researchers, the aforementioned favorable association could be the result of specific disease genes prevalent in long livers. Various types of allele genes have been proposed.^30
–32 Furthermore, the role of genes in minimizing the “speed” of aging and offering protection against age-related diseases could be an additional possible explanation.¹³ Recently, the role of different pathways (gender, etc) in aging and longevity has been reported.³³ Throughout the multivariate analysis, being female was associated with higher CVD morbidity. The latter finding is in accordance with previous results where females were living longer with higher burden of disease compared with males.³⁴

Research findings, however, lend support to the existence of genetic determinants for various CVD-RFs such as diabetes mellitus, metabolic syndrome, and others.^16,17 Various epidemiologic results suggest that parental, and in general familial aggregation of CVD events, is an additional strong determinant.³⁵ Although several international organizations²³ include parental CVD history as an independent factor in the assessment of CVD health, until now, it is rarely considered in the analysis of previous studies.¹⁸ For the first time, this study extends the analysis by including the maternal and parental CVD history (model 2) to show that the beneficial effect of parental longevity on offspring’s CVD health thus disappears. This finding indicates that the above-mentioned positive contribution of parental longevity could be mediated to those offspring who have an increased maternal and paternal burden of CVD-RFs.

It has been suggested that the process of long living reflects complex interrelations among multidimensional factors, which are represented throughout the successful aging concept.²⁰ Successful aging has been associated with lower mortality rates and better health outcomes.²⁹ The analysis of the MEDIS data revealed a beneficial effect of parental longevity on their offspring’s successful aging. However, this association was not significant any more after the inclusion of parental CVD-RF history (model 2). Until now, despite the sound evidence supporting the beneficial effect of parental longevity on various health indicators,¹⁸ the information about its role in the level of successful aging is sparse. Genomics, metabolomics,³⁶ and epigenetics³⁷ have been proposed as potential longevity pathways and could beneficially contribute to the favorable level of successful aging. Taking into account the aforementioned, the offspring of long livers seem to have a better successful aging status and a reduced risk for CVD age-related morbidities than the offspring of non–long-lived parents. This possible familial longevity and CVD health pathway raises some concerns about the need for early prevention measures in order to promote healthy long living, specifically among the offspring of non–long-lived parents and of parents with increased CVD morbidity. However, further studies are needed in the genetic predisposition of longevity, successful aging, and the role of parental burden of CVD-RFs.

Strengths and Limitations

The present study has several strengths. It is one of the few to evaluate the association of various factors (clinical, sociodemographic, and lifestyle), parental longevity, and CVD history of a large sample of “healthy,” independently living older people in the Mediterranean basin. Among the limitations, it is the fact that this is a cross-sectional study that limits the potential for etiological conclusions. Estimation of successful aging and of total CVD risk among elders is a difficult task.^20,38 The cumulative successful aging index, as well as the CVD scores that were used here by simply adding the presence of the common determinants of the individuals, may not accurately estimate the successful aging status and the CVD risk of these individuals. Also, in this study, there was the potential of recall bias, particularly in the assessment of parental CVD history.

Conclusion

Parental longevity seems to constitute an important factor of successful aging and CVD health of Mediterranean older adults. Our results suggest that older adults with long-lived parents retain a healthier CVD profile in their later life, a fact that further enhances the familial pathway of longevity and successful aging. However, further studies are needed to better address this interesting question on the role of hereditary in CVD health and successful aging.

Footnotes

Acknowledgments

The authors are particularly grateful to the men and women from the islands of Malta, Sardinia, Sicily, Mallorca, Menorca, Cyprus, Lesvos, Samothraki, Crete, Corfu, Lemnos, Zakynthos, Cephalonia, Naxos, Syros, Ikaria, Salamina, Kassos, Rhodes, Karpathos, Tinos, and the rural area of Mani, who participated in this research. They also wish to express their gratitude to M. Tornaritis, A. Polystipioti, and M. Economou (field investigators from Cyprus); K. Gelastopoulou and I. Vlachou (field investigator from Lesvos); I. Tsiligianni, M. Antonopoulou, N. Tsakountakis, and K. Makri (field investigators from Crete); E. Niforatou, V. Alpentzou, M. Voutsadaki, and M. Galiatsatos (field investigators from Cephalonia); K. Voutsa, E. Lioliou, and M. Miheli (field investigator from Corfu); S. Tyrovolas, G. Pounis, A. Katsarou, E. Papavenetiou, E. Apostolidou, G. Papavassiliou, and P. Stravopodis (field investigators from Zakynthos); E. Tourloukis, V. Bountziouka, A. Aggelopoulou, K. Kaldaridou, and E. Qira (field investigators from Syros and Naxos); D. Tyrovolas (field investigators from Kassos); I. Protopappa (field investigator from Ikaria); C. Prekas, O. Blaserou, and K. D. Balafouti (field investigators from Salamina); S. Ioakeimidi (field investigator from Rhodes and Karpathos); A. Mariolis (field investigator from Mani); S. Piscopo (field investigator from Malta); J. A. Tur (field investigator from Mallorca and Menorca); G. Valacchi and B. Nanou (field investigators from Sardinia and Sicily) for their substantial assistance in the enrolment of the participants.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by research grants from the Hellenic Heart Foundation, and therefore, we would also like to thank Prof Pavlos Toutouzas, Director of the Foundation. Stefano Tyrovola’s work was supported by the Foundation for Education and European Culture (IPEP), the Sara Borrell postdoctoral program (reference no. CD15/00019 from the Instituto de Salud Carlos III (ISCIII—Spain), and the Fondos Europeo de Desarrollo Regional (FEDER). Josep A. Tur was funded by grants PI11/01791, CIBERobn CB12/03/30038, and CAIB/EU 35/2001.

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