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TYPE Original Research

PUBLISHED 05 December 2024
DOI 10.3389/fcvm.2024.1386378

Additive interaction of family

medical history of cardiovascular
EDITED BY
Bobby Khan,
University of Central Florida, United States
diseases with hypertension and
REVIEWED BY
Aditya Goyal,
diabetes on the diagnosis of
Montefiore Health System, United States
Ye-Xuan Cao, cardiovascular diseases among
Capital Medical University, China

*CORRESPONDENCE older adults in India

Waquar Ahmed
[email protected]
Waquar Ahmed1*, Priyanka Dixit1 and Shiva Halli2
RECEIVED 19 February 2024
1
ACCEPTED 18 November 2024 School of Health Systems Studies, Tata Institute of Social Sciences, Mumbai, India, 2Department of
PUBLISHED 05 December 2024
Community Health Sciences, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

CITATION
Ahmed W, Dixit P and Halli S (2024) Additive
interaction of family medical history of
Introduction: The present study aimed to examine the additive interaction of
cardiovascular diseases with hypertension and family medical history of cardiovascular disease (CVD) and self-reported
diabetes on the diagnosis of cardiovascular hypertension and diabetes on the diagnosis of CVD among older adults aged
diseases among older adults in India. 45 years and above in India. A family medical history of CVD in individuals
Front. Cardiovasc. Med. 11:1386378.
with hypertension and diabetes could identify a subpopulation with a higher
doi: 10.3389/fcvm.2024.1386378
risk of CVD.
COPYRIGHT
Methods: The study used the data from the Longitudinal Ageing Study in India
© 2024 Ahmed, Dixit and Halli. This is an
open-access article distributed under the (LASI) Wave 1 (2017–2018). The total sample size for the study was 58,734 older
terms of the Creative Commons Attribution adults aged 45 years and above. An additive model was applied to determine the
License (CC BY). The use, distribution or
additive interaction effect of the family medical history of CVD with hypertension
reproduction in other forums is permitted,
provided the original author(s) and the and diabetes on the diagnosis of CVD by calculating three different measures of
copyright owner(s) are credited and that the additive interaction: the relative excess risk due to interaction (RERI), attribution
original publication in this journal is cited, in
proportion due to interaction (AP), and synergy index (S).
accordance with accepted academic practice.
No use, distribution or reproduction is Results: The prevalence of CVD was higher among hypertensive individuals with
permitted which does not comply with a family medical history of CVD (18.6%) than individuals without the coexistence
these terms.
of family medical history of CVD and hypertension (4.7%), and hypertensive
individuals without family medical history of CVD (11.3%). On the other hand,
the prevalence of CVD was higher among individuals with diabetes and family
history of CVD (20.5%) than individuals without the coexistence of family
history of CVD and diabetes (5.0%). Individuals with parental and sibling
medical history had two times higher odds of having chronic heart diseases
and strokes, respectively than those without parental and sibling history. In the
adjusted model, RERI, AP, and S for CVD were 2.30 (95% CI: 0.87–3.74), 35%
(0.35; 95% CI: 0.20–0.51), and 1.71 (95% CI: 1.27–2.28) respectively,
demonstrating significant positive interaction between family medical history
and hypertension on the diagnosis of cardiovascular diseases.
Conclusions: The present study revealed that in the additive model, the
interaction effects of family medical history and hypertension were
significantly positive on cardiovascular diseases even after adjustment with
potential confounding factors. Therefore, it is crucial to consider the presence
of family medical history of CVD among individuals with hypertension and
diabetes measured in research and clinical practice.

KEYWORDS

additive interaction, synergistic effect, family medical history, hypertension, diabetes,

cardiovascular diseases, older adults, India

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Ahmed et al. 10.3389/fcvm.2024.1386378

Introduction Materials and methods

Family history of non-communicable diseases is a significant Data
non-modifiable risk factor for various conditions, including
coronary heart disease (1), stroke (2), diabetes (3), hypertension This study used the data from the Longitudinal Ageing Study
(4), as well as breast cancer, lung cancer, colorectal cancer, in India (LASI) Wave 1 (2017–2018), a large-scale sample survey
prostate cancer, and ovarian cancer (5). Family history is a for the current analysis. The survey has been conducted under
significant indicator of genetic factors, and it is frequently the Ministry of Health and Family Welfare (MoHFW),
employed as an alternative measure to investigate the association Government of India. International Institute for Population
between genetic factors and diseases (6–9). According to Sciences (IIPS) collaborated with Harvard T. H. Chan School of
estimates by the American Heart Association, approximately Public Health and the University of Southern California. The
13.8% of American adults aged 20 years and older reported survey collected information on the health, economic, social, and
having a family history of heart disease (10). Existing literature demographic aspects of India’s ageing population as well as its
suggests that ischemic stroke and coronary heart disease are consequences. The LASI is a nationally representative survey that
heritable (10–12). Additionally, one prior study has shown that a included 72,250 individuals who were 45 years of age or older
family medical history of premature coronary heart disease along with their spouses (irrespective of age) in all Indian states
(angina, myocardial infarction, angioplasty, or bypass surgery) and union territories of India except Sikkim. The LASI employs
was significantly associated with a nearly 50% increase in the a multistage stratified area probability cluster sampling to select
lifetime risk for both coronary heart disease and cardiovascular the eventual units of observation. The LASI provides information
disease mortality (13). A recent study demonstrated that heart on chronic health conditions, biomarkers, symptom-based health
disease was more prevalent among individuals with hypertension, conditions, and functional and mental health. The LASI survey
diabetes, and family medical history of heart diseases (14). was carried out using a three-stage and four-stage sampling
High blood pressure, beyond its well-established association design in rural and urban areas, respectively. In each state/UT,
with coronary heart disease and stroke, is a significant risk factor Primary Sampling Units (PSUs) were chosen in the first stage,
for heart failure, atrial fibrillation, chronic kidney disease, heart while villages in rural areas and wards in urban areas were
valve diseases, aortic syndromes, and dementia (10, 15–17). chosen in the selected PSUs in the second stage. Households
Additionally, in a meta-analysis, it has been shown that 20 mm were selected from each identified village in the third stage;
Hg increase in systolic blood pressure and 10 mm Hg increase in however, sampling in urban areas required an additional stage,
diastolic blood pressure was significantly associated with a which comprised randomly selecting one Census Enumeration
twofold risk of mortality due to stroke, ischemic heart disease Block (CEB) in each urban area. From each CEB, households
(IHD) and other vascular diseases (18, 19). In a previous study, were selected in the fourth stage. The main goal was to select a
it was reported that relying solely on hypertension as a predictor representative sample at each stage of sample selection.
of individual risk of CVD is insufficient. Hereditary factors may The LASI used computer-assisted personal interview (CAPI)
elucidate why some specific hypertensive individuals are more technology for the data collection. This method required field
susceptible to CVD and why certain ethnic groups have a higher teams to be outfitted with laptop computers pre-loaded with
incidence of hypertension-related CVD (20). survey questions asked of respondents in a face-to-face interview.
In the ageing population, diabetes is a significant risk factor for The report contains considerable information on the survey
the development of cardiovascular disease (CVD) (21). Multiple design, data collection, and methodology. The present study is
studies demonstrated that individuals aged 40 to 75 with diabetes based on eligible respondents aged 45 years and above. The
face an intermediate or high risk of atherosclerotic cardiovascular present study is based on 65,562 respondents aged 45 years and
events (18, 21–23). Furthermore, the risk of CVD progressively above. After excluding 6,828 cases with missing information
increases with higher fasting plasma glucose levels, even before in any of the selected variables (including body mass index: 6,489,
reaching the diagnostic threshold for diabetes (24). hypertension, diabetes, and CVD: 185 and selected covariates), the
The presence of family history of CVD among individuals total sample size for the analysis was 58,734 respondents (Figure 1).
with hypertension and diabetes is relatively common, and their
coexistence may act synergistically on the risk of CVD. There is
a substantial gap in the literature concerning the interaction Measures
effect of family history with hypertension and diabetes on
cardiovascular diseases in low and middle-income countries Outcome variables
(LMICs), especially in India (20, 25). Thus, the current study
aimed to examine the additive interaction of family medical The outcome variables were self-reported chronic heart
history of CVD with self-reported hypertension and diabetes on diseases and stroke. In the study, respondents were asked, “Has
cardiovascular diseases. The findings on the significance of the any health professional ever diagnosed you with chronic heart
interaction effect are essential for developing an effective diseases such as coronary heart disease (heart attack or
holistic disease management strategy rather than disease- Myocardial Infarction), congestive heart failure, or other chronic
specific programs. heart problems?”. Respondents were also asked, “Has any health

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Ahmed et al. 10.3389/fcvm.2024.1386378

FIGURE 1
Study sample flowchart.

professional ever diagnosed you with a stroke?”. The responses as currently married, widowed, and others, not a union. Working
were coded as no and yes for each chronic disease and therefore status was coded as never worked, currently working, and currently
considered as self-reported. For the analysis, chronic heart not working. Alcohol use was coded as “no” and “yes”; smoking
diseases and stroke were combined to create CVD as one and chewing tobacco were coded as “never”, “former, and “current”
variable and coded it as no and yes. The BMI was computed by dividing the weight (in kilograms)
by the square of the height (in meters). BMI was coded according
to the criteria of the World Health Organisation’s classification; as
Key explanatory variable underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2),
overweight (25.0–29.9 kg/m2), and obesity (≥30.0 kg/m2), for the
The main explanatory variables were self-reported analysis, overweight and obesity were combined (26). The monthly
hypertension, diabetes and family medical history. In the study, per capita expenditure quintile (MPCE) or consumption quintile
respondents were asked, “Has any health professional ever was categorized into five quintiles, poorest, poor, middle, rich, and
diagnosed you with high blood pressure or hypertension?”. richest. Religion was categorized as Hindu, Muslim, Christian, and
Respondents were also asked, “Has any health professional ever Others. The social group (caste) was categorized as Scheduled
diagnosed you with diabetes?”. The responses were coded as no Castes (SC), Scheduled Tribes (ST), Other Backward Classes (OBC),
and yes for each chronic disease. In the LASI, to understand the and others. The “other” category in caste is identified as non SC,
genetic risk factors for cardiovascular diseases, information was ST, and non OBC caste. The place of residence was coded as urban
collected about the respondent’s family medical history; family and rural. The regions were categorized as North, Central, East,
medical history of the father, mother, brother, and sister were Northeast, West, and South. difficulty in activities of daily living
selected for the analysis. (ADL) and difficulty in instrumental activities of daily living
(IADL) was coded as “no” and “yes” (27).
To investigate the level of physical activities, respondents were
Other covariates asked the type and amount of physical activity involved in daily
life. For vigorous activities, respondents were asked “How do you
Age was coded as 45–54 years, 55–64 years, 65–74 years and 75 + often take part in sports or vigorous activities such as running or
years. Sex was coded as male and female. Education was recoded as no jogging, swimming, going to health centre/gym, cycling, digging with
education, primary, secondary, and higher. Marital status was coded a spade or shovel, heavy lifting, chopping, farm work, fast bicycling,

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Ahmed et al. 10.3389/fcvm.2024.1386378

and cycling with loads?”. For moderate activities, respondents were proportion of the combined effect that is attributable to the
asked “How do you often take part in sports or activities that are interaction between two factors. Finally, the S is a measure of the
moderately energetic such as cleaning house, washing clothes by ratio between combined effect and individual effects, with a value
hand, fetching water or wood, drawing water from a well, greater than 1 indicating a synergistic interaction (32–34).
gardening, bicycling at a regular pace, walking at a moderate pace, Bivariate analysis (cross-tabulation) was conducted to examine
dancing, floor or stretching exercises?”. Every day, more than once the prevalence of chronic heart diseases, stroke and CVD with
a week, once a week, one to three times per month, and hardly selected variables. A chi-square test and bivariate analysis (cross-
ever or never were the possible responses for moderate and tabulation) were also conducted to examine the prevalence of
vigorous physical activities. For both moderate and vigorous chronic heart diseases, stroke and CVD with respect to the joint
activities, respondents were also asked “on the days you did effect of family medical history of chronic heart diseases, stroke
activity, how much time did you usually spend doing any activity?”. and CVD with hypertension and diabetes. Additionally,
Weekly time spent for both moderate and vigorous physical multivariable binary logistic regression analysis (35) was used to
activity was calculated (Moderate physical activity: Those who establish the association between cardiovascular diseases and
performed at least 150 min of moderate-intensity physical activity main explanatory variables (hypertension, diabetes and family
throughout the week. Vigorous physical activity: Those who medical history). The binary logistic regression model is usually
performed at least 75 min of vigorous-intensity physical activity put into a more compact form as follows:
throughout the week). For both moderate and vigorous activities,
respondent was categorized as physically active (engagement more
Logit [P(Y ¼ 1)] ¼ b0 þ b  X
than once a week) or physically inactive (engagement once a week
or less often) based on the responses. Then physical activity
The parameter b0 estimates the log odds of outcome variables
variable was created as Physically active (Those who were either
for the reference group, while b estimates the maximum likelihood,
engaged in moderate physical activity or vigorous physical
the differential log odds of outcome variables associated with a set
activity) and otherwise physically inactive (28–31).
of predictors X, compared to the reference group. In this study, the
multivariable logistic regression and additive interaction models
were adjusted for potential confounding factors, including age,
Statistical analysis
sex, education, working status, marital status, residence, MPCE,
religion, caste, region, physical inactivity, smoking, chewing
Unadjusted and adjusted estimates were calculated using
tobacco, alcohol consumption, ADL, IADL, and body mass index
multivariable logistic regression models to assess the joint effect
(BMI). The survey weights were applied during the analysis to
of family medical history of CVD with hypertension and diabetes
account for sample clustering and present population estimates.
on the diagnosis of CVD. An additive model was applied to
All the analyses were conducted using Stata version 14.1 (36).
determine the additive interaction effect by calculating three
different measures of additive interaction: the relative excess risk
due to interaction (RERI), attribution proportion due to
interaction (AP), and synergy index (S) (30, 32, 33). Survey Results
weights were applied to calculate the three different measures of
additive interaction in the unadjusted and adjusted additive Table 1 presents the sample characteristics. A proportion of
model. Confidence intervals of these three measures were 34.5% of the participants were 65 years and older in this study.
estimated, and P < 0.05 was considered statistically significant. About 54% of the sample population was female. A large
The interaction measures on an additive scale are defined as: proportion of the sample (50.5%) had no education, and 73.9%
RERI (Relative excess risk due to interaction) = OR11 - OR10 - were in marital union during the survey. Further majority of the
OR01 + 1 sample population belonged to rural areas (70.1%).
AP (Attributable proportion to interaction) = RERI/OR11 Table 2 depicts the prevalence of chronic heart diseases, stroke
S (Synergy index) = (OR11 – 1)/(OR10 – 1) + (OR01 – 1) and cardiovascular diseases (CVD) among adults aged 45 years and
RERI =0 indicates no interaction, RERI > 0 indicates positive above. The overall prevalence of chronic heart diseases, stroke and
interaction, RERI < 0 indicates negative interaction, AP = 0 CVD was 3.8% (95% CI: 3.4, 4.4), 1.7% (95% CI: 1.5, 1.8), and 5.3%
indicates no interaction, AP > 0 indicates positive interaction, (95% CI: 4.8, 5.8), respectively. The prevalence of chronic heart
AP < 0 indicates negative interaction, S = 1 indicates no diseases (6.0%) was higher among those 65–74 years of age
interaction, S > 1 indicates positive interaction, S < 1 indicates group, while the prevalence of stroke (2.8%) was higher among
negative interaction (30, 32–34). individuals 75 years of age and above. The prevalence of chronic
Interaction on an additive scale means that the combined effect heart diseases (4.2% vs. 3.6%) and stroke (2.1% vs. 1.3) were
of two exposures is larger (or smaller) than the sum of the higher among males than female respondents. The prevalence of
individual effects of the two exposures. The RERI is a measure of chronic heart diseases (5.8% vs. 3.0%), stroke (1.9% vs. 1.6%),
departure from additivity, which reflects the excess risk of the and CVD (7.3% vs. 4.4%) was higher among those living in
outcome (total combined effect) due to the interaction between urban areas than individuals living in rural areas. Moreover, the
two factors. The AP, on the other hand, is a measure of the results show that the prevalence of chronic heart diseases

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TABLE 1 Sample characteristics, longitudinal ageing study in India. TABLE 1 Continued

Variables N % Variables N %
Sociodemographic variables Chewing tobacco
Age group Never 45,799 76.41

45–54 21,790 35.09 Former 1,436 2.38

55–64 18,232 30.46 Current 11,438 21.20

65–74 13,025 24.03 Alcohol Use

75+ 5,626 10.42 No 48,105 84.83

Sex Yes 10,568 15.17

Male 27,177 45.90 BMI categories

Female 31,496 54.10 Normal 30,665 51.57

Education level Underweight 10,859 21.34

No education 27,521 50.45 Overweight/obese 17,149 27.09

Primary 14,661 23.43 Physical inactivity

Secondary 10,865 16.29 Active 37,904 65.77
Higher 5,626 9.83 Inactive 20,769 34.23

Working status Morbidity

Never worked 16,040 25.98 Difficulty in ADL
Currently working 27,357 47.28 No 50,737 84.47
Currently not working 15,276 26.74 Yes 7,936 15.53
Marital status Difficulty in IADL
Currently married 43,977 73.94 No 39,646 63.47
Widowed 12,824 23.24 Yes 19,027 36.53
D/S/D/Others 1,872 2.82
Hypertension
Place of residence No 41,918 73.00
Rural 38,395 70.11 Yes 16,755 27.00
Urban 20,278 29.89
Diabetes
Caste No 51,188 88.08
Scheduled caste 9,878 19.41 Yes 7,485 11.92
Scheduled tribe 10,266 8.64
Family medical history
OBC 22,157 45.47
Others 16,372 26.47 Family history
No 52,313 88.39
MPCE quintiles
Yes 6,360 11.61
Poorest 11,549 20.98
Poorer 11,859 21.28 Parental FH
Middle 11,867 20.47 No 54,134 91.33
Richer 11,844 19.69 Yes 4,539 8.67
Richest 11,554 17.57 FH of father
Region No 55,943 94.46
North 10,816 12.71 Yes 2,730 5.54
Central 8,062 21.08 FH of mother
East 10,617 23.91 No 56,465 96.12
Northeast 7,583 3.38 Yes 2,208 3.88
West 7,705 15.94
Sibling FH
South 13,890 22.98
No 56,403 96.27
Religion Yes 2,270 3.73
Hindu 43,060 82.49
FH of brother
Muslim 6,951 11.05
No 56,936 97.10
Christian 5,878 2.95
Yes 1,737 2.90
Others 2,784 3.51
FH of sister
Lifestyle factors No 58,017 98.96
Smoking tobacco Yes 656 1.04
Never 47,880 82.74 Total 58,673 100.00
Former 2,671 3.78
%: weighted percentages to account for survey design and to provide national population
Current 8,122 13.48 estimates; ADL, activities of daily living; IADL, instrumental activities of daily living;
(Continued) MPCE, monthly per capita consumption expenditure; FH, family medical history (family
medical history of chronic heart disease, stroke and CVD).

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TABLE 2 Prevalence of chronic heart diseases, stroke, and cardiovascular diseases with respect to various background characteristics among older
adults in India.

Background characteristics Chronic heart diseases Stroke CVD

N % (95% CI) N % (95% CI) N % (95% CI)
Sociodemographic variables
Age group
45–54 420 2.1 (1.6,2.6) 176 0.9 (0.7,1.1) 576 2.8 (2.4,3.3)
55–64 686 3.6 (3.3,4.1) 268 1.6 (1.3,1.9) 917 4.9 (4.5,5.4)
65–74 703 6 (4.4,8.1) 321 2.5 (2.1,2.9) 984 8.1 (6.5,10.2)
75+ 325 5.5 (4.2,7.2) 160 2.8 (2.3,3.5) 459 8.0 (6.6,9.7)

Sex
Male 1,151 4.2 (3.7,4.6) 555 2.1 (1.9,2.4) 1,630 6 (5.5,6.5)
Female 983 3.6 (2.8,4.6) 370 1.3 (1.1,1.5) 1,306 4.7 (3.9,5.7)

Education level
No education 719 2.8 (2.4,3.2) 373 1.4 (1.2,1.7) 1,055 4.1 (3.7,4.5)
Primary 600 4.3 (3.6,5.1) 258 2 (1.7,2.4) 829 6 (5.3,6.8)
Secondary 522 6.0 (3.8,9.3) 190 2 (1.7,2.5) 678 7.6 (5.4,10.7)
Higher 293 4.6 (3.7,5.6) 104 1.5 (1.1,2.0) 374 5.7 (4.8,6.9)

Working status
Never worked 652 4.8 (3.3,6.9) 209 1.4 (1.1,1.6) 831 5.9 (4.4,8.0)
Currently working 583 2.2 (1.9,2.5) 227 0.8 (0.7,1.0) 783 2.9 (2.6,3.2)
Currently not working 899 5.8 (5.1,6.6) 489 3.4 (3.0,3.9) 1,322 8.8 (8.0,9.6)

Marital status
Currently married 1,596 3.7 (3.3,4.0) 677 1.6 (1.4,1.8) 2,173 5 (4.6,5.4)
Widowed 492 4.7 (3.1,7.1) 231 2.1 (1.7,2.5) 701 6.6 (4.9,8.8)
D/S/D/Others 46 1.5 (0.9,2.4) 17 0.6 (0.3,1.3) 62 2.1 (1.4,3.1)

Place of residence
Rural 1,060 3.0 (2.7,3.3) 535 1.6 (1.4,1.8) 1,543 4.4 (4.1,4.8)
Urban 1,074 5.8 (4.4,7.6) 390 1.9 (1.6,2.2) 1,393 7.3 (5.9,9.0)

Caste
Scheduled caste 302 3.4 (2.6,4.3) 169 2 (1.6,2.4) 455 5.1 (4.2,6.0)
Scheduled tribe 154 1.2 (0.9,1.7) 117 1 (0.7,1.4) 258 2 (1.6,2.5)
OBC 816 3.9 (3.0,5.1) 323 1.4 (1.2,1.6) 1,107 5.2 (4.2,6.3)
Others 862 4.9 (4.5,5.4) 316 2.1 (1.8,2.5) 1,116 6.7 (6.1,7.3)

MPCE quintiles
Poorest 297 2.7 (2.2,3.3) 123 1.2 (0.9,1.5) 405 3.7 (3.2,4.3)
Poorer 321 2.9 (2.3,3.6) 177 1.6 (1.3,1.9) 488 4.4 (3.7,5.1)
Middle 410 3.4 (2.9,4.1) 194 1.7 (1.4,2.0) 574 4.8 (4.2,5.6)
Richer 477 3.8 (3.3,4.3) 196 1.7 (1.4,2.1) 645 5.2 (4.6,5.8)
Richest 629 6.9 (4.8,10.0) 235 2.3 (1.9,2.7) 824 8.8 (6.6,11.7)

Region
North 525 4.1 (3.6,4.6) 148 1.5 (1.2,1.9) 645 5.3 (4.7,5.9)
Central 137 1.8 (1.5,2.3) 98 1.2 (0.9,1.5) 225 2.8 (2.4,3.4)
East 380 4.1 (3.5,5.0) 200 2.1 (1.8,2.5) 545 5.9 (5.1,6.7)
Northeast 140 2.7 (2.1,3.4) 97 1.3 (0.9,1.8) 228 3.9 (3.2,4.7)
West 307 4.9 (4.2,5.7) 165 2.4 (2.0,2.9) 451 7 (6.2,7.9)
South 645 4.7 (3.0,7.1) 217 1.3 (1.1,1.6) 842 5.9 (4.2,8.2)

Religion
Hindu 1,473 3.6 (3.1,4.3) 652 1.6 (1.4,1.8) 2,036 5 (4.4,5.7)
Muslim 427 5.3 (4.6,6.1) 132 2 (1.6,2.5) 536 6.9 (6.1,7.8)
Christian 142 4.2 (2.9,6.1) 78 1.4 (0.8,2.4) 213 5.6 (4.0,7.7)
Others 92 3.6 (2.6,5.0) 63 2.7 (1.9,4.0) 151 6.3 (4.9,8.0)

Lifestyle factors
Smoking tobacco
Never 1,650 3.7 (3.1,4.3) 694 1.5 (1.4,1.7) 2,257 5 (4.4,5.6)
Former 235 9.8 (7.3,13.1) 88 3.7 (2.6,5.2) 305 12.7 (10.0,15.9)
Current 249 3.2 (2.6,3.9) 143 2 (1.6,2.5) 374 5 (4.3,5.8)
(Continued)

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TABLE 2 Continued

Background characteristics Chronic heart diseases Stroke CVD

N % (95% CI) N % (95% CI) N % (95% CI)
Chewing tobacco
Never 1,752 4.0 (3.4,4.7) 733 1.7 (1.5,1.9) 2,379 5.5 (4.9,6.2)
Former 90 8.0 (4.9,13.0) 46 3.4 (2.4,5.0) 131 11 (7.5,15.7)
Current 292 2.7 (2.3,3.2) 146 1.4 (1.1,1.8) 426 3.9 (3.4,4.4)

Alcohol use
No 1,784 3.9 (3.4,4.6) 712 1.6 (1.4,1.8) 2,397 5.3 (4.7,6.0)
Yes 350 3.3 (2.8,3.9) 213 2.1 (1.7,2.5) 539 5.1 (4.5,5.8)

BMI categories
Normal 1,047 3.6 (3.2,4.0) 494 1.8 (1.6,2.0) 1,481 5.2 (4.7,5.6)
Underweight 213 2.1 (1.7,2.5) 123 1.3 (1.0,1.6) 326 3.2 (2.8,3.7)
Overweight/obese 874 5.7 (4.2,7.7) 308 1.7 (1.5,2.1) 1,129 7.1 (5.6,9.0)

Physical inactivity
Active 1,167 3.4 (2.7,4.2) 421 1.2 (1.0,1.3) 1,540 4.4 (3.7,5.2)
Inactive 967 4.8 (4.2,5.4) 504 2.6 (2.3,3.0) 1,396 7 (6.4,7.7)

Morbidity
Difficulty in ADL
No 1,642 3.4 (2.8,4.0) 579 1.2 (1.1,1.4) 2,151 4.4 (3.9,5.1)
Yes 492 6.3 (5.4,7.5) 346 4.1 (3.5,4.7) 785 9.8 (8.7,11.0)

Difficulty in IADL
No 1,224 3.0 (2.7,3.4) 389 1 (0.9,1.1) 1,563 3.9 (3.6,4.3)
Yes 910 5.2 (4.1,6.7) 536 2.8 (2.5,3.2) 1,373 7.7 (6.5,9.1)

Hypertension
No 775 1.8 (1.6,2.1) 326 0.9 (0.8,1.0) 1,080 2.6 (2.4,2.9)
Yes 1,359 9.3 (7.7,11.2) 599 3.8 (3.4,4.3) 1,856 12.4 (10.7,14.2)
Diabetes
No 1,466 2.9 (2.7,3.2) 661 1.4 (1.2,1.5) 2,058 4.1 (3.9,4.4)
Yes 668 10.7 (7.5,14.9) 264 3.8 (3.2,4.6) 878 13.6 (10.4,17.6)

Family medical history

Family history
No 1,724 3.5 (3.0,4.1) 789 1.5 (1.3,1.6) 2,262 4.8 (4.2,5.4)
Yes 410 8.0 (6.7,9.5) 136 4.9 (3.9,6.2) 674 9.2 (8.1,10.4)

Parental FH
No 1,868 3.6 (3.1,4.2) 830 1.5 (1.4,1.7) 2,475 4.9 (4.4,5.5)
Yes 266 7.9 (6.2,9.9) 95 4.6 (3.5,6.0) 461 8.9 (7.6,10.5)

FH of father
No 1,979 3.7 (3.2,4.3) 870 1.6 (1.4,1.7) 2,648 5.1 (4.5,5.6)
Yes 155 8.2 (5.9,11.1) 55 4.7 (3.3,6.7) 288 9 (7.2,11.1)

FH of mother
No 1,998 3.8 (3.3,4.3) 877 1.6 (1.5,1.8) 2,658 5.1 (4.6,5.7)
Yes 136 7.3 (5.6,9.4) 48 4.5 (3.0,6.5) 278 9.1 (7.6,10.9)

Sibling FH
No 1,950 3.7 (3.2,4.3) 877 1.6 (1.5,1.8) 2,691 5.1 (4.5,5.6)
Yes 184 9.3 (7.5,11.6) 48 6.4 (4.3,9.4) 245 10.9 (9.2,12.9)

FH of brother
No 1,991 3.7 (3.2,4.3) 887 1.6 (1.5,1.8) 2,711 5.1 (4.6,5.7)
Yes 143 10.2 (8.0,13.0) 38 6.9 (4.4,10.6) 225 11.6 (9.6,14.1)

FH of sister
No 2,082 3.8 (3.3,4.4) 911 1.7 (1.5,1.8) 2,849 5.2 (4.7,5.8)
Yes 52 7.9 (4.9,12.5) 14 5.4 (2.6,10.8) 87 9.2 (6.6,12.9)
Total 2,134 3.8 (3.4,4.4) 925 1.7 (1.5,1.8) 2,936 5.3 (4.8,5.8)

%: weighted percentages to account for survey design and to provide national population estimates; CVD, cardiovascular diseases; ADL, Activities of daily living; IADL, Instrumental activities of
daily living, MPCE, Monthly per capita consumption expenditure; FH, family medical history (family medical history of chronic heart disease, stroke and CVD).

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Ahmed et al. 10.3389/fcvm.2024.1386378

(4.8% vs. 3.4%), stroke (2.6% vs. 1.2%) and CVD (7.0% vs. 4.4%) those without coexistence of family medical history and
were higher among physically inactive participants than those hypertension (3.5% and 1.5%), hypertensive individuals without
who were physically active. Chronic heart diseases (8.0% vs. family medical history (8.6% and 3.3%), and individuals with
3.5%), stroke (4.9% vs. 1.5%), and CVD (9.2% vs. 4.8%) were family medical history and without hypertension (3.6% and 2.5%).
more prevalent among those who had a family history of
respective chronic diseases than individuals without family
The prevalence of CVD, chronic heart diseases
medical history. The prevalence of chronic heart diseases and
and stroke based on the presence or absence of
stroke was 9.3% and 3.8% among individuals with hypertension.
family medical history and diabetes
Further, the prevalence of chronic heart diseases and stroke was
Our findings show that the prevalence of CVD was higher
10.7% and 3.8% among individuals with diabetes. The prevalence
among individuals with the coexistence of diabetes and family
of cardiovascular diseases was higher among individuals with
history of CVD (20.5%, 95% CI: 16.8–24.8) than individuals
hypertension (12.4% vs. 2.7%) and diabetes (13.6% vs. 4.1%)
without coexistence of a family history of CVD and diabetes
than those without hypertension and diabetes.
(5.0%, 95% CI: 4.5–5.6), individuals with diabetes and without a
Table 3 illustrates the prevalence of chronic heart diseases,
family history of CVD (12.7%, 95% CI: 9.1–17.4), individuals
stroke and CVD with respect to the key predictor variables
with a family history of CVD and without diabetes (7.5%, 95%
among individuals aged 45 and above.
CI: 6.5–8.8), and individuals without the presence of both family
medical history of CVD and diabetes (3.7%, 95% CI: 3.4–4.0).
Moreover, the results indicate that the prevalence of chronic
The prevalence of CVD, chronic heart diseases heart diseases and stroke was higher among individuals with the
and stroke based on the presence or absence of coexistence of family medical history and diabetes (18.2% and
family medical history and hypertension 10.7%) than individuals without coexistence of family medical
The results indicate that the prevalence of CVD was higher history and diabetes (3.7% and 1.6%), individuals with diabetes
among hypertensive individuals with family medical history of and without family medical history (10.0% and 3.4%), and
CVD (18.6%, 95% CI: 16.1–21.3) than individuals without the individuals with a family medical history and without diabetes
coexistence of family medical history of CVD and hypertension (6.4% and 4.1%).
(4.7%, 95% CI: 4.2–5.3), hypertensive individuals without a Table 4 presents the unadjusted and adjusted logistic regression
family medical history of CVD (11.3%, 95% CI: 9.5–13.5), estimates for chronic heart disease, stroke and cardiovascular
individuals with the presence of family medical history of CVD diseases by hypertension, diabetes, and family medical history of
and without hypertension (4.4%, 95% CI: 3.6–5.4), and cardiovascular diseases (any family history, parental history, father,
individuals without the presence of both family medical history mother, sibling history, brother and sister) among older adults aged
of CVD and hypertension (2.4%, 95% CI: 2.2–2.7). 45 years and above in India. Figure 2 presents the adjusted logistic
Moreover, the results indicate that the prevalence of chronic regression estimates for chronic heart disease, stroke and
heart diseases and stroke was higher among hypertensive cardiovascular diseases by hypertension, diabetes, and family
individuals with family medical history (16.2% and 9.4%) than medical history of cardiovascular diseases (any family history,

TABLE 3 Prevalence of chronic heart diseases, stroke, and cardiovascular diseases with respect to combined effect of the key predictor variables among
older adults in India.

Variables Chronic heart diseases Stroke Cardiovascular diseases

N % (95% CI) P-value N % (95% CI) P-value N % (95% CI) P-value
FH and hypertension 0.000 0.000 0.000
No 1,858 3.5 (3.0,4.1) 831 1.5 (1.4,1.7) 2,486 4.7 (4.2,5.3)
Yes 276 16.2 (13.4,19.5) 94 9.4 (7.2,12.3) 450 18.6 (16.1,21.3)
FH and diabetes 0.000 0.000 0.000
No 1,994 3.7 (3.2,4.3) 882 1.6 (1.5,1.8) 2,709 5.0 (4.5,5.6)
Yes 140 18.2 (14.0,23.3) 43 10.7 (7.0,16.1) 227 20.5 (16.8,24.8)
FH#Hypertension 0.000 0.000 0.000
0.FH#0.hypertension 641 1.7 (1.5,2.0) 284 0.8 (0.7,0.9) 856 2.4 (2.2,2.7)
0.FH#1.hypertension 1,083 8.6 (6.9,10.7) 505 3.3 (2.9,3.8) 1,406 11.3 (9.5,13.5)
1.FH#0.hypertension 134 3.6 (2.7,4.8) 42 2.5 (1.7,3.7) 224 4.4 (3.6,5.4)
1.FH#1.hypertension 276 16.2 (13.4,19.5) 94 9.4 (7.2,12.3) 450 18.6 (16.1,21.3)
FH#Diabetes 0.000 0.000 0.000
0.FH#0.diabetes 1,196 2.6 (2.4,2.9) 568 1.2 (1.1,1.4) 1,611 3.7 (3.4,4.0)
0.FH#1.diabetes 528 10.0 (6.7,14.8) 221 3.4 (2.8,4.1) 651 12.7 (9.1,17.4)
1.FH#0.diabetes 270 6.4 (5.2,7.9) 93 4.1 (3.1,5.3) 447 7.5 (6.5,8.8)
1.FH#1.diabetes 140 18.2 (14.0,23.3) 43 10.7 (7.0,16.1) 227 20.5 (16.8,24.8)
Total 2,134 3.8 (3.4,4.4) 925 1.7 (1.5,1.8) 2,936 5.3 (4.8,5.8)

FH, family medical history.

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TABLE 4 Multivariable logistic estimates for cardiovascular diseases according to key predictor variables among individuals aged 45 years and above.

Key Variables Chronic heart diseases Stroke Cardiovascular diseases

UOR 95% CI AOR 95% CI UOR 95% CI AOR 95% CI UOR 95% CI AOR 95% CI
Hypertension
No Ref. Ref. Ref. Ref. Ref. Ref.
Yes 5.51*** (4.32 7.02) 3.77*** (3.14 4.51) 4.41*** (3.63 5.34) 3.48*** (2.82 4.28) 5.18*** (4.29 6.26) 3.73*** (3.23 4.31)

Diabetes
No Ref. Ref. Ref. Ref. Ref. Ref.
Yes 3.98*** (2.68 5.90) 2.37*** (1.85 3.02) 2.83*** (2.27 3.52) 2.18*** (1.72 2.75) 3.65*** (2.67 5.00) 2.35*** (1.91 2.89)

Family history of CVD

Ref. Ref. Ref. Ref. Ref. Ref.
Yes 2.39*** (1.86 3.08) 2.09*** (1.64 2.65) 3.45*** (2.66 4.46) 3.07*** (2.33 4.03) 2.03*** (1.68 2.45) 1.86*** (1.56 2.23)

Parental FH
No Ref. Ref. Ref. Ref. Ref. Ref.
Yes 2.27*** (1.70 3.05) 2.07*** (1.55 2.78) 3.10*** (2.30 4.18) 2.76*** (2.01 3.80) 1.90*** (1.54 2.34) 1.80*** (1.47 2.20)

FH of father
No Ref. Ref. Ref. Ref. Ref. Ref.
Yes 2.32*** (1.60 3.36) 2.07*** (1.40 3.04) 3.04*** (2.06 4.50) 2.64*** (1.77 3.94) 1.86*** (1.43 2.42) 1.75*** (1.35 2.27)

FH of mother
No Ref. Ref. Ref. Ref. Ref. Ref.
Yes 2.01*** (1.46 2.76) 1.79*** (1.31 2.44) 2.85*** (1.89 4.29) 2.49*** (1.60 3.89) 1.86*** (1.48 2.34) 1.68*** (1.33 2.12)

Sibling FH
No Ref. Ref. Ref. Ref. Ref. Ref.
Yes 2.68*** (2.01 3.56) 2.08*** (1.58 2.74) 4.22*** (2.75 6.45) 3.45*** (2.22 5.36) 2.30*** (1.84 2.88) 1.89*** (1.52 2.37)

FH of Brother
No Ref. Ref. Ref. Ref. Ref. Ref.
Yes 2.95*** (2.16 4.02) 2.31*** (1.71 3.13) 4.52*** (2.79 7.32) 3.58*** (2.16 5.94) 2.46*** (1.93 3.14) 2.00*** (1.56 2.56)

FH of Sister
No Ref. Ref. Ref. Ref. Ref. Ref.
Yes 2.18** (1.28 3.69) 1.70* (1.03 2.80) 3.39** (1.59 7.27) 2.99** (1.41 6.35) 1.84** (1.25 2.72) 1.56* (1.06 2.29)

*p < 0.05, **p < 0.01; ***p < 0.001; UOR, unadjusted odds ratio; AOR, adjusted odds ratio; Ref, reference category; AOR, adjusted for age, sex, education, working, marital status, residence,
MPCE, religion, caste, region, physical inactivity, smoking, chewing tobacco, alcohol consumption, body mass index, ADL and IADL.

parental history, father, mother, sibling history, brother and sister). brother, sister medical history had significantly 2.64, 2.49, 3.58,
The result indicates that individuals with hypertension had 3.77 and 2.99 times higher odds of having stroke, respectively
[Adjusted odds ratio (AOR): 3.77, CI: 3.14–4.51] and 3.48 (AOR: compared with those without family medical history.
3.48, CI: 2.82–4.28) times higher odds of chronic heart disease and Table 5 provides the multivariable logistic regression estimates
stroke, respectively, than those without hypertension. Participants of chronic heart diseases, stroke, and CVD by the joint effect of
with diabetes had significantly higher odds of having chronic heart family history of cardiovascular diseases with hypertension and
diseases and stroke than those without diabetes. diabetes. This table also provides unadjusted and adjusted models
Our finding further shows that individuals with family medical of additive interaction of family history with hypertension and
history had higher odds of chronic heart diseases (AOR: 2.09, CI: diabetes on chronic heart diseases, stroke and CVD. Figure 3
1.64 2.65) and stroke (AOR: 3.07, CI: 2.33 4.03) than those shows the adjusted model of additive interaction between family
without family history. Moreover, individuals with parental and medical history and hypertension on the diagnosis of
sibling medical history had 2.07-and 2.09-times higher odds of cardiovascular diseases. Figure 4 shows the adjusted model of
having chronic heart diseases, respectively, than those without additive interaction between family medical history and diabetes
parental and sibling history. Moreover, our findings demonstrate on the diagnosis of cardiovascular diseases.
that individuals with father, mother, brother, sister medical
history had significantly 2.07, 1.79, 2.31, and 1.70 times higher Interaction effect of family history and
odds of having chronic heart diseases, respectively compared hypertension on chronic heart diseases, stroke,
with those without family medical history. and CVD
Similarly, individuals with parental and sibling medical history Our results show that the AOR of the joint effect between
had 2.76-and 3.58-times higher odds of having stroke, respectively, family history and hypertension on the diagnosis of CVD was
than those without parental and sibling history. Moreover, our 6.57 (95% CI: 5.20–8.31). In the adjusted model, the relative
findings further demonstrate that individuals with father, mother, excess risk due to interaction (RERI) value for CVD was 2.30

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Ahmed et al. 10.3389/fcvm.2024.1386378

FIGURE 2
Multivariable logistic estimates for cardiovascular diseases according to key predictor variables among individuals aged 45 and above. Odds ratio,
adjusted for age, sex, education, working, marital status, residence, MPCE, religion, caste, region, physical inactivity, smoking, chewing tobacco,
alcohol consumption, body mass index, ADL and IADL. FH, family medical history (family history of chronic heart diseases, stroke, and
cardiovascular diseases).

(95% CI: 0.87–3.74), which indicates that there is a significant which demonstrates that the combined effect is more than the
positive interaction between family history and hypertension on sum of the individual effects of family history and hypertension
the diagnosis of cardiovascular diseases. The attributable on the risk of developing chronic heart diseases, stroke and CVD
proportion due to interaction (AP) value was 35% (0.35; 95% CI: among older adults aged 45 years and above in India. The result
0.20–0.51), which suggests that a significant proportion of CVD also shows that the interaction effect is higher for stroke than
cases in the population can be attributed to the interaction chronic heart diseases.
between family history and hypertension. The synergistic effect
index (S) was 1.71 (95% CI: 1.27–2.28), further supporting a Subgroup analysis
significant synergistic effect. We performed subgroup analysis based on age, gender,
Furthermore, our findings show that the AOR of the joint effect residence and education analysis to measure the interaction effect
between family history and hypertension on the diagnosis of chronic of family medical history and hypertension on cardiovascular
heart diseases and stroke were 7.52 (95% CI: 5.57–10.15) and 9.54 diseases (Supplementary Table S1). Interestingly, our results
(95% CI: 6.62–13.76). In the adjusted model, the RERI values for demonstrated significant positive interaction effects between
chronic heart diseases and stroke were 2.99 (95% CI: 0.89–5.06), family medical history and hypertension on cardiovascular
and 4.23 (95% CI: 0.90–7.57), respectively, which indicates that diseases on an additive scale among male respondents [chronic
there is a significant positive interaction between family history heart diseases[RERI: 2.27, AP: 35.76%, S: 1.74], stroke [RERI:
and hypertension on the diagnosis of chronic heart diseases and 5.19, AP: 50.52%, S: 2.27], and CVD [RERI: 2.51, AP: 38.98%, S:
stroke. The AP values were 39% (0.39; 95% CI: 0.21–0.58) and 1.86]], female respondents [chronic heart diseases [RERI: 4.21,
44% (0.44; 95% CI: 0.22 0.66), which suggests that a significant AP: 44.96%, S: 2.01], and CVD [RERI: 2.31, AP: 33.13%,
proportion of chronic heart diseases and stroke cases in the S: 1.63]], those aged 55–64 years [CVD (RERI: 2.48, AP: 34.34%,
population can be attributed to the interaction between family S: 1.66)], urban residents [chronic heart diseases [RERI: 3.66,
history and hypertension. Additionally, the S values were 1.84 AP: 50.76%, S: 2.43], stroke [RERI: 6.66, AP: 55.35%, S: 2.52],
(95% CI: 1.28–2.66) and 1.98 (95% CI: 1.24–3.15), respectively, and CVD [RERI: 3.14, AP: 47.03%, S: 2.24]], no education
which further supports a significant synergistic effect. [stroke (RERI: 8.70, AP: 63.33%, S: 3.16)], secondary education
The RERI, AP and S all present consistent results as they all [chronic heart disease (RERI: 4.25, AP: 47.44%, S: 2.15)] and
show significant positive interaction effect on an additive scale, higher education [CVD (RERI: 6.44, AP: 61.75%, S: 3.15)].

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TABLE 5 Additive interaction of family medical history of CVD with hypertension and diabetes on cardiovascular diseases among individuals aged 45 and
above in India.

Chronic heart diseases Stroke Cardiovascular diseases

Model 1 Model 2 Model 1 Model 2 Model 1 Model 2
A | Hypertension
Additive interaction between family history and hypertension
0.FH#0.hypertension Ref. Ref. Ref. Ref. Ref. Ref.
0.FH#1.hypertension 5.42*** (4.09 7.17) 3.67*** (3.00 4.49) 4.28*** (3.48 5.28) 3.4*** (2.72 4.25) 5.08*** (4.04 6.38) 3.61*** (3.06 4.26)
1.FH#0.hypertension 2.17*** (1.56 3.02) 1.86*** (1.32 2.61) 3.16*** (2.03 4.90) 2.91*** (1.85 4.57) 1.82*** (1.43 2.33) 1.66*** (1.30 2.12)
1.FH#1.hypertension 11.19*** (8.58 14.58) 7.52*** (5.57 10.15) 12.87*** (9.16 18.09) 9.54*** (6.62 13.76) 9.10*** (7.40 11.19) 6.57*** (5.20 8.31)

Measures of interaction on an additive scale (P-value, 95% CI)

RERI 4.60; 0.002 (1.66 7.54) 2.99; 0.005 (0.89 5.06) 6.43; 0.003 (2.23 10.62) 4.23; 0.012 (0.90 7.57) 3.18; 0.001 (1.26 5.11) 2.30; 0.001 (0.87 3.74)
AP$ 41.10; 0.000 (0.22 0.60) 39.73; 0.000 (0.21 0.58) 49.94; 0.000 (0.31 0.69) 44.34; 0.000 (0.22 0.66) 35.02; 0.000 (0.19 0.51) 35.07; 0.000 (0.20 0.51)
S 1.82; 0.001 (1.27 2.61) 1.84; 0.001 (1.28 2.66) 2.18; 0.000 (1.44 3.31) 1.98; 0.003 (1.24 3.15) 1.65; 0.001 (1.23 2.21) 1.71; 0.000 (1.27 2.28)

B | Diabetes
Additive interaction between family history and diabetes
0.FH#0.diabetes Ref. Ref. Ref. Ref. Ref. Ref.
0.FH#1.diabetes 4.10*** (2.60 6.45) 2.43*** (1.84 3.23) 2.82*** (2.22 3.58) 2.19*** (1.70 2.82) 3.77*** (2.58 5.52) 2.41*** (1.88 3.10)
1.FH#0.diabetes 2.53*** (1.97 3.25) 2.21*** (1.70 2.87) 3.43*** (2.54 4.64) 3.07*** (2.23 4.23) 2.12*** (1.76 2.56) 1.95*** (1.61 2.35)
1.FH#1.diabetes 8.22*** (5.92 11.43) 4.90*** (3.42 6.99) 9.69*** (5.99 15.68) 7.03*** (4.24 11.63) 6.71*** (5.18 8.69) 4.36*** (3.27 5.80)

Measures of interaction on an additive scale (P-value, 95% CI)

RERI 2.59; 0.111 (−0.60 5.79) 1.25; 0.189 4.44; 0.063 (−0.23 9.12) 2.76; 0.126 (−0.77 6.30) 1.82; 0.103 (−0.37 4.01) 0.99; 0.156 (−0.38 2.36)
(−0.62 3.11)
AP$ 31.60; 0.049 (0.00 0.63) 25.51; 45.82; 0.001 (0.18 0.74) 39.33; 0.017 (0.09 0.72) 27.11; 0.057 22.75; 0.089
0.103 (−0.05 0.56) (−0.01 0.55) (−0.04 0.49)
S 1.56; 0.109 (0.91 2.69) 1.47; 0.16 (0.86 2.51) 2.04; 0.016 (1.14 3.67) 1.85; 0.060 (0.97 3.50) 1.47; 0.110 (0.92 2.35) 1.42; 0.133 (0.89 2.24)

*p < 0.05, **p < 0.01; ***p < 0.001; Ref, reference category; FH, family medical history (family history of chronic heart diseases and stroke, cardiovascular diseases).
Interaction exists if RERI ! = 0 or AP ! = 0 or S ! = 1.
Model 1: Unadjusted model.
Model 2: Adjusted for age, sex, education, working, marital status, residence, MPCE, religion, caste, region, physical inactivity, smoking, chewing tobacco, alcohol consumption, body mass index
(BMI), ADL and IADL.
RERI, Relative excess risk due to interaction.
AP, Attributable proportion, AP$, the attributable proportion, has been presented in the result as a percentage after multiplied by 100, S, Synergy index.
RERI, AP, and S values have been presented in bold.

Interaction effect of family history and diabetes on Subgroup analysis

chronic heart diseases, stroke and CVD We performed subgroup analysis based on age, gender, residence
The results suggest that the AOR of the joint effect between and education analysis to measure the interaction effect of family
family history and diabetes on the diagnosis of chronic heart medical history and diabetes on cardiovascular diseases
diseases, stroke and CVD were 4.9 (95% CI: 3.42 6.99), 7.03 (Supplementary Table S2). Interestingly, our results revealed
(95% CI: 4.24 11.63) and 4.36 (95% CI: 3.27 5.80). However, significant positive interaction effects between family medical
RERI, AP, and S showed inconsistent results with 95% CI history and diabetes on cardiovascular diseases on an additive scale
significance in the unadjusted and adjusted model on chronic among male respondents (CVD) and those aged 55–64 years (CVD).
heart diseases, stroke and CVD. In the adjusted model on
chronic heart diseases, our finding shows consistent results, Male respondents and those aged 55–64 years
RERI = 1.25 (95% CI: −0.062 3.11), AP = 25% (0.25; 95% CI: The results showed that in the adjusted model, among male
−0.05 0.56), and S = 1.47 (95% CI: 0.86 2.5), indicating positive respondents and individuals aged 55–64 years, the RERI values for
but insignificant interaction on an additive scale. Similarly, in the CVD were 1.64 (95% CI: 0.02–3.26) and 3.16 (95% CI: 0.67–5.65),
adjusted model on CVD, our finding shows insignificant results, respectively, which indicates that there is a significant positive
RERI = 0.99 (95% CI: −0.062 2.36), AP = 22.75% (0.2575; 95% interaction between family history and diabetes on the diagnosis of
CI: −0.04 0.49), and S = 1.32 (95% CI: 0.89 2.24), indicating cardiovascular diseases. The AP values were 38.43% (0.38; 95% CI:
insignificant interaction on an additive scale. 0.13–0.64), and 53.38% (0.53; 95% CI: 0.32–0.75), respectively,
Moreover, our finding shows inconsistent results on stroke, RERI = which suggests that a significant proportion of CVD cases in the
2.76 (95% CI: −0.77 6.30), AP = 39% (0.39; 95% CI: 0.09 0.72), and S = population can be attributed to the interaction between family
1.85 (95% CI: 0.97 3.67), with one measure AP, suggesting positive and history and diabetes. The S values were 2.01 (95% CI: 1.14–3.55),
significant interaction effect on stroke, which suggests that a significant and 2.80% (2.80; 95% CI: 1.50–5.20), respectively, further
proportion of stroke cases in the population can be attributed to the supporting a significant synergistic effect. This means that the
interaction between family history of stroke and diabetes. combined effect of family medical history and diabetes on the risk

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FIGURE 3
Additive interaction of family medical history of CVD with hypertension on cardiovascular diseases among individuals aged 45 and above in India. FH,
family medical history (family history of chronic heart diseases, stroke, and cardiovascular diseases); HT, hypertension. Interaction exists if RERI ! = 0 or
AP ! = 0 or S ! = 1. Estimates for Additive Interaction, adjusted for age, sex, education, working, marital status, residence, MPCE, religion, caste, region,
physical inactivity, smoking, chewing tobacco, alcohol consumption, body mass index (BMI), ADL and IADL. RERI, Relative excess risk due to
interaction; AP, Attributable proportion, AP, the attributable proportion, has been presented in the result as a percentage after multiplied by 100.
S, Synergy index.

FIGURE 4
Additive interaction of family medical history of CVD with diabetes on cardiovascular diseases among individuals aged 45 and above in India. FH, family
medical history (family history of chronic heart diseases, stroke, and cardiovascular diseases); Db, diabetes. Interaction exists if RERI ! = 0 or AP ! = 0 or
S ! = 1. Estimates for Additive Interaction, adjusted for age, sex, education, working, marital status, residence, MPCE, religion, caste, region, physical
inactivity, smoking, chewing tobacco, alcohol consumption, body mass index (BMI), ADL and IADL. RERI, Relative excess risk due to interaction.
AP, Attributable proportion, AP, the attributable proportion, has been presented in the result as a percentage after multiplied by 100. S, Synergy index.

of developing CVD is greater than the sum of their individual effects Our findings show that the prevalence of chronic heart diseases
among male respondents and those aged 55–64 years. (8.0%) and stroke (4.9%) were more than two times higher among
those who had family medical history compared to those without
family medical history of chronic heart disease (3.5%) and stroke
Discussion (1.5%) among older adults aged 45 years and above in India. A
recent study showed that the prevalence of chronic heart disease
The current study presents the interaction effect of family was higher among individuals with family medical history (14).
medical history of cardiovascular diseases with hypertension and Blood relatives commonly share genetic predispositions to
diabetes on the diagnosis of cardiovascular diseases. The study conditions like high blood pressure, heart disease, or stroke.
revealed a significant positive interaction on an additive scale Genes, hereditary units passed down from parents to children,
between family medical history of cardiovascular diseases and can contribute to this predisposition (37). Our finding shows that
hypertension on cardiovascular diseases as observed through all individuals with family medical history had higher odds of
three measures (RERI, AP and S), even after adjustment with chronic heart diseases and stroke than those without family
lifestyle and socio-demographic factors. medical history. A recent study demonstrated that the odds of

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Ahmed et al. 10.3389/fcvm.2024.1386378

heart disease were higher among individuals with family medical interaction effect of family medical history and diabetes on
history (14). Consistently, one previous study demonstrated that stroke, which suggests that a significant proportion of stroke
individuals with a family history had higher odds of cases in the population can be attributed to the interaction
cardiovascular diseases (38). between family history of stroke and diabetes. Moreover,
The current study further demonstrates that individuals with subgroup analysis demonstrates the significant positive
parental and sibling medical history had two times higher odds interaction effects between family medical history and diabetes
of having chronic heart diseases and strokes, respectively than on CVD on an additive scale among male respondents and those
those without parental and sibling history. A previous study aged 55–64 years. A recent study revealed that genome-wide
demonstrated that participants with at least one parent with genetic risk scores showed a stronger association with coronary
premature cardiovascular disease had a higher risk of CVD artery disease (CAD) in men compared to women for both
events than those without a parental history of cardiovascular existing and newly developed cases of CAD (42). A prior study
disease (39). Moreover, our findings present that individuals showed that in both men and women, the presence of diabetes
with paternal and maternal medical history had nearly 2.6- and and a family history of early coronary heart disease significantly
2.5-times higher odds of having stroke, respectively, compared increased the risk of developing coronary heart disease so that
with those without family medical history. Concordantly, one for individuals with diabetes and a positive family history of the
prior study presented that positive paternal family history disease, approximately 74% of coronary heart disease cases could
was associated with a twofold increase in stroke risk, be attributed to the interaction between these factors (43).
while maternal family history increased the risk by The heightened risk of heart disease linked to a family history
approximately 40% (2). can be attributed to common genetic, environmental, and
Moreover, significant modifiable risk factors for CVD are behavioral factors (38). Epigenetic mechanisms, through various
hypertension, smoking, diabetes mellitus, and lipid abnormalities types of reactions, are recognized as key mediators of the
(16). Our results show that the prevalence of CVD was higher interaction between genes and the environment, potentially
among individuals with hypertension (12.4%) and diabetes explaining the association between diabetes and cardiovascular
(13.6%) compared to those without hypertension (2.6%) and disease (44). In the case of hypertension, epigenetic changes are
without diabetes (4.1%). Previous studies reported that diabetes is influenced by intrauterine environmental factors that may impair
a well-established risk factor for cardiovascular diseases, nephron development, as well as by factors affecting autonomic
including coronary heart disease, heart failure, peripheral artery responsiveness, vascular remodeling, salt sensitivity, and the
disease and stroke (40). On the other hand, hypertension is renin-angiotensin system (44).
associated with the strongest evidence of causation and is
highly prevalent (16).
Interaction refers to the situation in which the effect of one Implication for policy, practice and
exposure on the outcome depends on the level of another future research
exposure (33, 34, 41). Our findings indicate that the
prevalence of CVD was higher among hypertensive individuals It has been established that a positive family history of CVD is
with family medical history of CVD (18.6%) than individuals an independent predictor of both myocardial infarction (45, 46)
without the coexistence of family history of CVD and and stroke (47–49). Including both hypertension and family
hypertension (4.7%) and hypertensive individuals without history in prognostic models for stroke leads to higher predictive
family history of CVD (11.3%). One prior study demonstrated value compared to models that consider only hypertension or
that hypertensive individuals with a positive family history of family history alone (48). A familial medical history of premature
CVD had a nearly twofold higher prevalence of vascular hypertension and cardiovascular diseases is considered a crucial
disease compared to hypertensive individuals without a initial indicator of a genetic predisposition to hypertension and
family history of CVD (20). Further, our results show that CVD. This circumstance may warrant clinically indicated genetic
there is a significant positive interaction on the additive scale testing (15). Among individuals with higher genetic
between family history of cardiovascular diseases and predisposition, preventive strategies may confer substantial
hypertension on the diagnosis of cardiovascular diseases, benefits. A previous study reported that among individuals at
which shows that the combined effect is more than the sum of higher genetic risk, adherence to a favorable lifestyle was found
the individual effects of family history and hypertension on to be associated with approximately 50% lower relative risk of
the risk of developing cardiovascular diseases among older coronary heart disease compared to those who adhered to an
adults aged 45 years and above in India. The result also shows unfavorable lifestyle (50). Previous studies present considerable
that the interaction effect is higher for stroke than chronic evidence supporting the benefit of blood pressure-lowering
heart disease. A previous study revealed that among medication in the prevention of atherosclerotic cardiovascular
individuals with hypertension, a family history of CVD was disease among adults with moderate to high cardiovascular risk
significantly associated with a higher prevalence of non-stroke and systolic blood pressure (SBP) ≥ 130 mm Hg or diastolic
CVD and stroke (20). blood pressure (DBP) levels ≥80 mm Hg. These studies reveal a
Interestingly, our finding shows inconsistent results on stroke, substantial reduction in adverse outcomes, including stroke, heart
with one measure AP (39.0%), suggesting positive and significant failure, coronary events, and mortality (18, 51, 52).

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Ahmed et al. 10.3389/fcvm.2024.1386378

The study’s outcomes hold significant implications for the Data availability statement
standard clinical care of individuals diagnosed with
cardiovascular diseases (CVD). Accordingly, it is advised to Publicly available datasets were analyzed in this study. The
conduct thorough monitoring of patients exhibiting blood study uses secondary data which is available upon reasonable
pressure readings nearing the upper threshold of the normal request through: https://www.iipsindia.ac.in/content/lasi-wave-i.
range, particularly those with a family history of CVD. As a The data are also available in the repository of the Gateway to
result, concerted efforts should be undertaken to proactively Global Aging Data (https://g2aging.org).
prevent blood pressure elevation in this specific population.

Ethics statement
Limitations and strengths
The studies involving human participants were reviewed and
The cross-sectional nature of the study precludes the
approved by the Indian Council of Medical Research (ICMR)
establishment of causal relationship. However, it is crucial to
extended the necessary guidelines and ethics approval for
emphasize that this is a cross-sectional study, and our findings
undertaking the LASI survey. The participants provided their
rely on self-reported information regarding hypertension,
written informed consent to participate in this study.
diabetes, cardiovascular diseases and family medical history.
There is a possibility of recall bias that cannot be entirely
eliminated. The current study also provides the information
Author contributions
about those who were on medication for cardiovascular
diseases, which minimizes the recall bias. It is essential to
WA: Supervision, Conceptualization, Data curation, Formal
recognize these limitations while interpreting the findings of
Analysis, Investigation, Methodology, Resources, Software,
this study. Despite the limitations, the current study has
Validation, Visualization, Writing – original draft, Writing –
potential strengths. In LASI, for those who reported that they
review & editing. PD: Conceptualization, Supervision, Writing –
have been diagnosed with a disease by a medical professional, a
review & editing. SH: Writing – review & editing, Supervision.
set of additional questions relating to the diagnosing physician,
the date of diagnosis, and if currently taking treatment were
asked. This is the first population-based cross-sectional study
Funding
with a large sample size that investigated the additive
interaction of family medical history of cardiovascular diseases
The author(s) declare that no financial support was received for
with hypertension and diabetes on cardiovascular diseases.
the research, authorship, and/or publication of this article.
Additional research using robust study designs, such as
prospective cohort studies or randomized controlled trials,
is needed to investigate further and validate the observed
additive interactions.
Conflict of interest
The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could
Conclusions be construed as a potential conflict of interest.

The present study revealed that in the additive model,

the interaction effects of family medical history and Publisher’s note
hypertension were significantly positive on cardiovascular
diseases. A family medical history of CVD can be used as a All claims expressed in this article are solely those of
valuable tool to identify hypertensive individuals at a higher the authors and do not necessarily represent those of
risk. Understanding the interaction between family history their affiliated organizations, or those of the publisher, the
of cardiovascular diseases and hypertension is crucial for editors and the reviewers. Any product that may be
effective risk assessment, prevention, and team-based evaluated in this article, or claim that may be made
management strategies. Further, regular cardiovascular by its manufacturer, is not guaranteed or endorsed by
screenings, monitoring blood pressure, and addressing the publisher.
modifiable risk factors are essential in managing and reducing
the risk of cardiovascular disease among individuals with
family medical history and diagnosed with hypertension. Supplementary material
Consequently, a positive family history can be employed to
engage immediate family members in health education The Supplementary Material for this article can be found
initiatives and implement early interventions for improved online at: https://www.frontiersin.org/articles/10.3389/fcvm.2024.
hypertension and cardiovascular management. 1386378/full#supplementary-material

Frontiers in Cardiovascular Medicine 14 frontiersin.org

Ahmed et al. 10.3389/fcvm.2024.1386378

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