Study model and data sources

In this retrospective investigation, a multilevel analysis was conducted in stages. In the initial phase, we obtain data for the dependent variable from the CVD outcome, including data on cardiovascular diseases, ischemic heart disease, and ischemic stroke mortality rate and incidence rate per 100,000. By accumulating data on Summary exposure value (SEV) for the high BMI, hyperglycemia, high systolic blood pressure, dyslipidemia, and smoking, independent variable data were collected. The Institute of Health Metrics and Evaluation (IHME), an impartial health research center at the University of Washington, collected all the dependent and independent variables from 34 provinces in Indonesia between 2000 and 2019 using publicly accessible datasets. Next, covariates on the GINI index, health facilities, and GDP per capita were added. Covariates were included in the multivariate regression analysis.

Metabolic and behavioural risk factors

Exposure to risk factors contributing to the escalation number of Disability-Adjusted Life Years (DALYs) and mortality rate attributed to CVD namely hypertension, dyslipidemia, hyperglycemia, obesity, smoking was computed as the Summary Exposure Value (SEV). A measure of a population’s risk factor exposure that considers the extent of exposure by risk level as well as the severity of that risk’s contribution to disease burden. SEV has a value of zero when there is no extra risk in a population and a value of one when the population is at the maximum degree of risk; we present SEV on a scale of 0% to 100% to indicate that it is risk-weighted prevalence. The parameter data for the dependent variables (hyperglycemia, obesity, dyslipidemia, hypertension, and smoking) were obtained through the examination of high glucose level, high body mass index, high low-density lipoprotein, high systolic blood pressure and smoking from 34 provinces in Indonesia. High blood pressure when SBP is greater than 110–115 mm Hg; high body mass index when BMI is greater than 21.0–24.0 kg/m2; high fasting plasma glucose when greater than 4.9–5.3 mmol/L; dyslipidemia when total cholesterol is greater than 3.8–4.0 mmol/L; and smoking any tobacco product.

Cardiovascular diseases outcome; incidence and death

Mortality rates, the number of deaths per 100,000 people, and incidence rate owing to cardiovascular diseases, ischemic heart disease, or stroke by gender, province, and year, were used as dependent variables throughout the study. Age-standardized data were used to compare populations with different age structures. Population characteristics were statistically transformed to match those of a reference population. Year lag analysis was added for incidence to determine the rate at which new events occur in a defined population owing to the risk factors. From 2000 to 2019, data were collected continuously.

Covariates

In this study, covariates were used to examine the analysis affecting the independent variables. First, we compiled the Socio-demographic Index from 2000 to 2019 for each province in Indonesia, totaling 34 provinces. The values vary from 0 to 1, with 0 being the greatest disparity and 1 indicating equality. Data were acquired from the Indonesian Ministry of Health profile, a publicly open-source data. GDP Per Capita, is the next covariate to be considered. Finally, we included the number of health centers from the Indonesian Ministry of Health profile.

Death attributed to risk factors between 2000 to 2019

We calculated how much of the increase in cardiovascular disease death between 2000 and 2019 could be attributed to the prevalence of behavioral and metabolic risk factors during the same time. IHME provided the sex-specific population attributable fractions (PAF) of cardiovascular disease (CVD) events attributed to each risk factor (hyperglycemia, obesity, dyslipidemia, high systolic blood pressure, and tobacco). Prior research [3, 9] has produced an algorithm for calculating the number of fatalities averted or delayed due to changes in risk variables. The equation also includes the population attributable fractions (PAF) where it is used to determine the effect of changes in the prevalence of hyperglycemia, obesity, dyslipidemia, hypertension, and smoking to CVD. To compute this, the number of fatalities from each category of CVD in the basis year of 2005 was multiplied by the difference between the PAF from risk factors in the base year (2000) and the final year (2019). This figure was then multiplied by -1 to determine the number of fatalities that occurred because of changes in risk variables, as opposed to the number of deaths that were averted or postponed. Hence, a positive number represents the number of fatalities caused by a certain risk factor, and a negative number represents the number of deaths that were prevented/delayed. For instance, the PAF of High Body Mass Index increased from 0.1 to 0.18 and the baseline number of death due to CVD in 2000 were 380553, then, the additional cardiovascular disease deaths in 2019 that were related to an increasing prevalence of high BMI were consequently computed as follows:

Statistical analysis

A multivariate regression model using R software evaluated CVD outcome data as the dependent variable, SEV of each risk factor as the main independent variable, and the adjusted covariate. This study included CVD mortality and incidence rates per 100,000 people. Pearson clustered standard error tests avoided were used to autocorrelation. State fixed effects accounted for unobserved cultural, geographic, and historical characteristics between states but fixed over time. Year fixed effects controlled unseen elements that vary over time but are comparable across states. Fixed-effect models analyze aggregated health data well. Fixed effects control province variation that may affect study outcomes. Year fixed effects account for unobserved factors that fluctuate over time but affect all provinces equally. This controls time-specific effects on outcomes. Fixed-effects models handle unobserved variables that may confound aggregated health data, making the study more robust. This method isolates and estimates the variables of interest, improving the risk factor-health outcome link.

Ethic statement

This research did not require permission from an Ethics committee because it utilized solely data from publically accessible secondary databases.

Patient and public involvement statement

It was neither suitable nor feasible to include patients or the general public in the research’s conception, implementation, reporting, or dissemination plans.

CVD burden trend in developed and developing countries

Cardiovascular disease (CVD) is still the leading cause of mortality worldwide. A greater number of CVD deaths is found in countries going through economic transition such as India, China, and Russia. The explanation for this uptrend in CVD burden may be caused due to economic prosperity, which is associated with a high-fat diet, obesity, diabetes mellitus, tobacco use, and a sedentary lifestyle, all well-defined risk factors for developing CV disease [10]. This trend follows the same pattern observed in developing countries like Indonesia, where there has been a substantial incline in CVD incidence, prevalence, and mortality rates (RISKESDAS). Previous research in Indonesia indicated that approximately 470,000 people die annually due to CVD [11]. These findings also align with the trend observed in other developing countries such as China, where the mortality has been dramatically increased since the 1980s [12].

However, this pattern contrasts with well developed nations like the United States and Brazil, where there has been a decline in fatalities related to cardiovascular disease [2, 9]. Research conducted in Brazil revealed a decrease in cardiovascular disease mortality between 2005 and 2017, attributed to a reduction in smoking-related risk factors [2]. Meanwhile, United States depicted a similar trend which is due to significant advancements in evidence-based therapies, including thrombolysis, CABG, coronary angioplasty and stents, ACE inhibitors, and statins [9] In west countries, the decline in rates of cardiovascular mortality over the last four decades is secondary to several factors such as changes in population risk factors and improved health care [10].

The epidemiological features of the CVD epidemic in Asia further support the data in this study, which is continuous increase in CVD mortality rate, with a huge proportion of premature CVD deaths. The responsible CVD risk factors in most Asian countries are inadequate management of unhealthy diet, smoking, obesity, hypertension, dyslipidemia, and diabetes, along with the rapid progression of population aging in many Asian countries [13] Specifically in Southeast Asia, age-standardized CVD mortality rates range from 124.9 to 421.6 per 100,000 in 2021 and high systolic blood pressure accounted for the largest proportion of DALYs among all CVD risks, contributing to 56.9% death [14].

Identifying key factors contributing to escalating mortality rates

This study found that, in addition to an increase in cardiovascular disease mortality, there is an increase in the summary exposure value of several major risk factors for the occurrence and death from cardiovascular disease such as hypertension, obesity, diabetes mellitus, dyslipidaemia, and smoking.

Hypertension

In this study, we found that hypertension had the most significant number of risk variables when compared to other risk factors. Furthermore, hypertension has been dominating the most attributable CVD death among other risk factors for the past 19 years. Data from Basic Health Research (RISKESDAS) demonstrate that the prevalence of hypertension according to physician diagnosis and medication accounted for 8.36% and 8.84% respectively. On contrary, based on the blood pressure measurement, the prevalence of hypertension reaches as high as 34.11% (RISKESDAS). This depicts the occurrence of the condition called underdiagnosis in Indonesia. Other study also confirmed this state and identified that rural areas have a higher rate of underdiagnosis and higher wealth is more likely to undergo regular medical checkups and diagnosed as hypertension [15]. Besides, RISKESDAS also found that a significant portion of hypertension patients in Indonesia, around 32.27%, do not consume medication routinely, with 13.33% not taking any medication at all. The reasons are mainly because many people do not feel any symptomps (59.8%), lack of regular control (31.1%), the use of other traditional medications (14.5%), and forgetfulness (11.5%). Only 12% of all hypertension patients in Indonesia routinely measure their blood pressure (RISKESDAS). Undermedication for hypertension is important issue that also needs to be addressed. Study revealed that lower wealth groups were more likely to be undermedicated, particularly in rural areas [15]. Other risk factors such as older age, lower education levels, overweight or obesity, and healthcare utilization were associated with hypertension high number in Indonesia [16]. In terms of hypertension in adolescents, lifestyle and behavior changes, along with sex, family, nutritional status, physical activity, and most significantly, stress, were associated with hypertension occurrence among Indonesian adolescents [17]. Another study focused on coastal communities in Indonesia revealed increasing age and individuals with lower socioeconomic status had a higher risk of hypertension [18]. In fact, despite the high prevalence, hypertension is not always identified as the leading cause of death in certain studies, while playing a critical role in the development and progression of CVD [19].

In this study, hypertension is revealed to have a higher prevalence than any other risk factor; yet there does not appear to be a meaningful association between changes in hypertension exposure and rising mortality rates in Indonesia. Furthermore, it has been demonstrated that high LDL exposure in men has a substantial link with an increase in mortality, as does diabetes mellitus in women.

Obesity

This study highlights that the highest cardiovascular death portion is attributed to obesity or high BMI. High BMI is shown to be responsible to substantial number of deaths, primarily caused by CVD [20]. A review in general population has also depicted that obesity or high BMI is associated with an increased risk of CVD mortality [21]. Obesity plays an important role in CVD mortality by directly contributing to the development of other cardiovascular risk factors such as dyslipidemia, type 2 diabetes, hypertension, and sleep disorders [22]. Moreover, obesity is also evidenced to independently lead to cardiovascular mortality irrespective of other cardiovascular risk factors [23]. Adiposity, especially visceral or abdominal fat, is strongly linked to cardiovascular risk and disease through various physiological mechanisms, including metabolic, endocrinologic, immunologic, structural, humoral, hemodynamic, and functional alterations [22]. Furthermore, obesity is strongly associated with DKOLH-CVD (diabetes, chronic kidney disease, obesity, hyperlipidemia, or hypertensive heart disease). Regarding other countries data, DKOLH-CVD exhibits a significant proportion of CVD mortality in the US and Australia. Recent data indicate that the mortality rates associated with DKOLH-CVD have been increasing, especially at younger ages [24].

Overall, global trends in CVD incidence and mortality rates indicate a decline in most countries since 1990. However, developed nations have experienced a more significant reduction, while developing nations still face challenges in reducing the burden [25]. By examining the global and regional patterns of cardiovascular disease, it becomes evident that various factors such as economic transitions, lifestyle changes, and access to healthcare contribute to the varying trends observed across different countries and regions. These insights are crucial for the development of targeted prevention strategies and further research to address the challenges faced by different nations in combatting cardiovascular disease [1, 2, 9, 11, 12].

These findings could be attributed to the high-risk factor for Indonesian adults aged >40 years and the rates of preventive therapy are low [26]. In the Southeast Asian Region (SEAR), it has been observed that the onset of cardiovascular disease (CVD) tends to occur at a relatively young age. This means that individuals in this region are experiencing the development of CVD earlier in their lives compared to other regions [27]. Additionally, there is a concerning trend of premature death resulting from CVD, which is growing at a rapid pace. This alarming increase in premature CVD-related deaths further emphasizes the urgent need for effective preventive measures and interventions in the SEAR [26]. There is a notable recognition in high body mass index or obesity which is showed to dramatically increasing from 9% to 18% between 2000 to 2019 which is accounted for 37,864 and 118,188. Obesity’s SEV rate dramatically soared up from 6,7 to 16 (+9,3%). The results obtained from the comprehensive analysis conducted in this study have revealed a rather disconcerting pattern in the mortality rates associated with cardiovascular disease. Furthermore, it has been observed that this distressing trend is closely correlated with a notable surge in the overall level of exposure to various significant risk factors that are known to contribute the development and progression of this condition. The study sheds light on several key factors that play a crucial role in the development and mortality rates associated with cardiovascular disease. These factors include hypertension, obesity, diabetes mellitus, dyslipidaemia, and smoking. Each of these contributors has been found to have a substantial impact on the occurrence and severity of cardiovascular disease, ultimately leading to increased rates of mortality. We uncover a significant correlation between the escalation of plasma glucose exposure in women and a progressively higher deaths caused by ischemic heart disease. On the other hand, it is important to note that when there is an increase in LDL exposure, there is a notable and significant correlation that emerges. The data clearly indicates that as LDL exposure rises, there is a corresponding escalation in mortality rates from this cardiovascular condition.

Hyperglycemia

The present study demonstrates a strong association between elevated plasma glucose levels and increased death rates attributed to IHD among female individuals. This discovery aligns with the findings of a prior investigation conducted in Brazil, which demonstrated a positive association between elevated plasma glucose levels and cardiovascular mortality among women [2]. The higher prevalence of impaired glucose tolerance in women compared to males, as observed in a previous study conducted in Indonesia by the National Basic Health, is attributed mainly to Diabetes Mellitus [28]. The prevalence of Diabetes Mellitus has been observed to be positively associated with the incidence of obesity. This relationship is particularly evident in the period spanning from 2000 to 2019, during which the prevalence of obesity has demonstrated a consistent upward trend. Additionally, it has been noted in several studies that the prevalence of undiagnosed diabetes mellitus exceeds that of diagnosed cases. We also performed a sensitivity analysis to examine the relationship between elevated plasma glucose levels and the presence of Type II Diabetes Mellitus. The results of the analysis indicate a statistically significant association between these two variables and the increase in IHD mortality. There is evidence to suggest a positive association between those diagnosed with diabetes mellitus and increased rates of both all-cause death and cardiovascular mortality [6]. High fasting plasma glucose is defined by the Institute for Health Metrics and Evaluation (IHME) as exceeding the theoretical minimum risk exposure limit (TMREL), specifically falling within the range of 4.8–5.4 mmol/L or 86.4–97.2 mg/dL. However, another study established a correlation between hbA1C levels and cardiovascular disease (CVD) mortality, specifically when the hbA1C value exceeds or is equal to 7 [29].

Dyslipidemia

Similar trends have been observed in other developing nations across the globe, including the bustling city of Beijing and the beautiful archipelago of the Philippines. These nations, like many others, have experienced significant increases in total cholesterol levels, which is a key indicator of cardiovascular health. Additionally, there has been a higher prevalence of atherosclerosis risk factors in these regions, highlighting the urgent need for preventive measures and interventions to address this growing health concern.

This study found that, in addition to an increase in cardiovascular disease mortality, there is an increase in the summary exposure value of several major risk factors for the occurrence and death from cardiovascular disease, such as hypertension, obesity, diabetes mellitus, dyslipidemia, and smoking. This rise was observed in both genders, namely women and men. In this study, we found that hypertension had the most significant number of risk variables when compared to other risk factors. Nonetheless, the findings in this paper suggest that there is a significant association between the change in high plasma glucose exposure in women and the increasing number of ischemic heart disease deaths. We discovered a strong link between increased LDL exposure and rising ischemic heart disease death rates in males. These findings can be explained by the fact that, despite the high prevalence of hypertension, hypertension is not always identified as the leading cause of death in certain studies, while playing a critical role in the development and progression of CVD [19]. These findings are also consistent with previous studies in which men were more likely to smoke, eat a high-risk diet, and have a low HDL cholesterol level, whereas women were more likely to have a low physical activity level, the presence of mental-emotional disorders, obesity, a high WC, a high WtHR, hypertension, diabetes, a high total cholesterol level, and a high LDL cholesterol level [6].

Another research in a developing nation, Beijing, found the same thing, with the majority of the increase ascribed to significant increases in total cholesterol levels [12]. Additionally, it is comparable in other developing nations, such as the Philippines, where the prevalence of atherosclerosis risk factors was higher in 2018 than in 2003, despite a non-significant increase in diabetes and a drop in smoking [30].

Understanding the factors behind mortality decline in developed nations

The results here contrast with those of some affluent nations, such as the United States and Brazil, where fatalities from cardiovascular disease are falling [2, 3]. According to research done in Brazil, there has been a decline in cardiovascular disease mortality from 2005 to 2017, followed by a trend of reducing risk factors for smoking [2]. Meanwhile, in America, significant advances in evidence-based therapies, such as the use of thrombolysis, coronary artery bypass grafting (CABG), coronary angioplasty and stents, angiotensin-converting-enzyme (ACE) inhibitors, statins, have revolutionized the treatment of cardiovascular disease [3].

Another comprehensive research study was undertaken to delve deeper into the factors contributing to the decline in cardiovascular mortality rates in Maryland, USA. The significant decrease in cardiovascular disease rates can be attributed to the remarkable advancements in prevention and treatment strategies. These advancements have led to a rapid decline in cigarette smoking, better management of hypertension, widespread utilization of statins to reduce cholesterol levels, and the timely implementation of thrombolysis and stents in cases of acute coronary syndrome to minimize or even prevent heart attacks [31]. The prevention and control of main CHD risk factors, successful treatment of existing CHD, and possibly other unidentified factors affect CHD death rates. Due to the magnitude of these factors and their success in preventing CHD deaths, CHD trends vary by age, sex, race, ethnicity, geographic location, and other socio-demographic categories. Thus, CHD death rates may continue to drop in some populations at the spectacular rates seen in the US in the early 1970s [3].

In this study, we also investigate by incorporating many variables that potentially affect these risk factors into the multivariate model, including the covariates Socio-demographic Index, Primary health care coverage, and GDP per capita. Women still received the same results after we added these variables; that is, there was a substantial effect on mortality from cardiovascular disease and exposure to diabetes risk factors. After adjusting for this covariate in males, the research findings demonstrate a substantial effect of hypertension and obesity on the rise in stroke mortality in Indonesia.

We also continue the year lag analysis to see whether there is a relationship between risk variables in prior years and the rise in cardiovascular events in Indonesia. The findings of this study revealed that the risk factors for dyslipidaemia in the previous 2,5,8,10 years had a substantial effect on the rise in mortality from ischemic heart disease in both men and women. These findings differ from research in Brazil, in which practically all risk variables in the year-lag analysis contributed to a decrease in CVD mortality [2].

We hereby acknowledge some study limitations. This analysis included observational studies by independent researchers and nationwide government survey to assess risk factor exposure. Thus, those exposed to risk factors may have had a pre-existing cardiovascular disease, which could affect our findings. Despite the need to account for exposure and outcome measurement error, the Institute for Health Metrics and Evaluation (IHME) and Global Burden of Disease (GBD) studies have the largest databases in their disciplines. These findings support a large prospective study that linked modifiable risk variables to cardiovascular disease (CVD) mortality in 21 countries. In this study, multiple covariates were incorporated, including SDI, GDP per capita, and primary health care coverage. The data was categorized based on provinces and sourced from government records. However, it is important to note that in Indonesia, there was a modification in the number of provinces. Specifically, in 2012, two additional provinces, East Kalimantan, and North Kalimantan, were established, resulting in a total of 34 provinces. Consequently, there is a possibility of shared data between these two provinces, which could potentially influence the outcomes of this study.

The application of this research implies that the government should have become more aware of metabolic and behavioural risk factors as early as ten years ago and enhanced the regulation of preventive approaches and initiatives. The government can take proactive actions to lessen the burden of cardiovascular disease by detecting and addressing risk factors such as dyslipidaemia, diabetes mellitus, hypertension, poor diets, physical inactivity, and smoking. This strategy could include implementing comprehensive public health campaigns to promote healthier lifestyles, improving access to healthcare services for early detection and management of risk factors, and strengthening food labelling, tobacco control, and physical activity promotion regulations and policies. The government can successfully address the rising incidence of cardiovascular disease and enhance the overall cardiovascular health of the people by prioritizing preventative measures and taking a multi-sectoral strategy.

This research will help to strengthen Asia’s demographic database. It will provide useful insights into the health profiles of Asian communities by evaluating the prevalence and impact of cardiovascular risk factors such as dyslipidaemia, diabetes mellitus, hypertension, and behavioural variables. The findings can assist inform public health policy, resource allocation, and tailored interventions to address the Asian population’s special cardiovascular health requirements. Furthermore, by expanding the knowledge base on cardiovascular risk factors across Asia, this research will help to improve global understanding of cardiovascular disease and support efforts to develop more effective prevention and management strategies globally.