• „ REVIEW

The burden of cardiovascular disease risk factors: A current problem

Andrzej Pająk1, Piotr Jankowski2, 3, Tomasz Zdrojewski4

1Department of Epidemiology and Population Studies, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Kraków, Poland

2Department of Internal Medicine and Geriatric Cardiology, Center of Postgraduate Medical Education, Warszawa, Poland

3Department of Epidemiology and Health Promotion, School of Public Health, Center of Postgraduate Medical Education, Warsaw, Poland

4Department of Preventive Medicine and Education Medical University of Gdansk, Gdańsk, Poland

INTRODUCTION

In Poland, mortality from diseases of the circulatory system has been decreasing since 1991. After a large decline in the 1990s, the trend slowed down, and from 1999 to 2018, standardized death rates were decreasing by an average of 2.8% per year in men and 3.0% per year in women. A decreasing trend in mortality from heart diseases (but not cerebrovascular diseases) was even more conspicuous in the age group 25–64 years after 2014 for women and 2015 for men. Despite these favorable declining trends, the standardized rates of deaths due to diseases of the circulatory system are higher than the European average by about 40%, both for men and women [1]. According to the estimates of Bandosz et al., based on the IMPACT coronary heart disease (CHD) mortality model, about 54% of the reduction in the number of CHD deaths could be attributed to favorable changes in risk factors and about 37% to the advance in treatment methods. However, at that time, only 9% could be attributed to initial treatments for acute myocardial infarction [MI] or unstable angina, and the impact of invasive cardiology on mortality was small (barely 4%) [2, 3]. The year 2020 reversed the favorable trend of declining mortality due to cardiovascular disease, with the excess of about 62 thousand all-cause deaths that could not be explained by the demographic conversion of the population. Only 43% of these deaths were reported as caused by SARS-CoV-2 infections, and 27%, occurred in infected persons, but other underlying causes of death were reported for them. The remaining 29% were not reported as related to COVID-19. Overall, the largest increase of 17% was recorded for the diseases of the circulatory system [4].

There are observations that the COVID19 pandemic caused a significant reduction in the number of patients treated for atherosclerotic cardiovascular disease (CVD). Compared to pre-pandemic time, the number of hospitalizations for MI decreased by over 40%, and the number of coronary angiographies and percutaneous coronary interventions decreased by 30%. This coincided with about a 10% decrease in the number of State Emergency Medical Services calls due to chest pain [5–7]. Further, the lockdown in the early phase of COVID-19 and the adaptation of hospital wards to COVID-19 care could have caused a significant decrease in the number of hospital admissions of patients with other manifestations of CVD, as it was observed for atrial flutter and atrial fibrillation [8]. However, the supportive evidence is not strong enough to conclude that the increase of fatality due to the underuse of diagnostic and treatment procedures, in particular in the acute state, would explain fully the unprecedented rise in the number of CVD deaths during the COVID-19 pandemic. It is worth considering the other possible explanations.

In August 2021, an update of the European recommendations on cardiovascular disease prevention in clinical practice was published. This valuable document is the 7th version in the series which started in 1994 and aims to summarize the evidence to help health professionals in making decisions on the management strategies for individual patients [9]. The publication and promotion of the document turned the attention back to the impact of CVD risk factors on the health of the general population and the implications for public health, which might have seemed less important in the time of the COVID-19 pandemic.

In this article, we aimed to review the exposure to CVD risk factors in the Polish population and to discuss the evidence which indicates that preventive methods which aim to reduce risk factors are even more important in the times of COVID-19.

Exposure to main risk factors

Although population studies on CVD risk factors have a long history in Poland including the POL-MONICA [10, 11] and NATPOL [12, 13] surveys, more intensive investigations were carried out within the last two decades. Since 2000, six cross-sectional studies that aimed to examine independent national samples and two large studies that involved patients of primary care have been carried out (Table 1).

One of the important explanations for poor control of risk factors is that a cardiac rehabilitation program was offered to only one-third of CHD patients. The proportion of patients offered places in the rehabilitation programs remained on the same level between 1997 and 2017 [56, 57]. The new system of managed care for acute myocardial infarction survivors introduced in Poland later increased access to cardiac rehabilitation in participating cardiac centers. In patients covered by the new system, the rate of participation in outpatient cardiac rehabilitation was six times greater than in patients who were not. A smaller but notifiable evident was recorded for the participation rate in the inpatient cardiac rehabilitation that was higher by about 53% [58]. Earlier experience from an experimental study carried out in Polish CHD and high-risk patients suggested that a managed, comprehensive cardiac prevention and rehabilitation program is an effective lifesaving procedure [59]. Analysis of the new system of managed care confirm that improved access to cardiac rehabilitation, along with improved access to cardiac consultations and invasive treatment procedures, might contribute to the 30% lower risk of death, observed within 1 year after hospitalization in patients participating in the new system compared to those who are not [58]. However, no information is available on how much of the effect on mortality could be attributed to the reduction of risk factors.

Main benefits from risk factors control

There is overwhelming evidence on the causal relations between risk factors and atherosclerotic CVD [9]. Most of the reduction of mortality due to atherosclerotic CVD could likely be attributed to favorable changes in risk factors [2]. Two decades ago, European scientific societies under the leadership of the European Society of Cardiology (ESC) recommended an individual assessment of CVD risk using the information on age (rounded to a decade), sex, current smoking status, and categorized total cholesterol and blood pressure [60]. In 2021, in the 7th version of the ESC Guidelines on cardiovascular disease prevention in clinical practice, a new version of the scoring system (SCORE2 combined with SCORE2-OP) was introduced [9]. The new system allows for a more precise assessment of the risk of fatal and non-fatal atherosclerotic CVD by sex and five-year age groups for the broader age range, i.e. from 40 to 79 years. Then, instead of blood total cholesterol, the assessment requires information on blood non-HDL-C, which is easily deliverable and reflects better a concentration of LDL-C. Finally, the new system adopted an age-group dependent classification of low-, medium-, high- and very high CVD risk. SCORE 2 and SCORE 2 OP were elaborated in four versions for the four groups of countries according to the CVD death rates. Poland was classified as a high-risk country [61, 62].

Estimation of 10-year fatal or nonfatal CVD risk with SCORE2 or SCORE2-OP is recommended in apparently healthy people at the age over 39 years, without established atherosclerotic CVD, diabetes mellitus, chronic kidney disease, lipid disorder, or elevated BP [9]. This assessment aims to help physicians to identify patients at high risk, who would benefit most from the treatment. Further, the use of CVD risk tables or their electronic version may facilitate discussing patient treatment plans tailored to their individual needs.

The new value in the last version of the ESC guidelines is the “LIFE CVD model,” which allows for the assessment of the mean number of years free of CVD gained after quitting smoking and after lowering LDL-C or blood pressure. The assessment can be made for each risk group according to the SCORE2/SCORE-OP [9]. The number of years gained is higher in women and non-smokers, and the younger the age is, the greater is the number of years gained. Then, in general, the gain is related to the overall risk assessment, i.e. the greater the risk score is, the higher is the number of years free of CVD gained (Figure 1 and Figure 2). The system is novel in terms of its application to the general population and might appear to be very helpful in the promotion of prevention and discussions with individual patients.

Figure 1. CVD (cardiovascular disease)-free lifetime gain (in years) from smoking cessation for apparently healthy persons with systolic blood pressure 140–159 mm Hg and non-high-density lipoprotein-cholesterol (non-HDL-cholesterol) concentration 4.0–4.9 mmol/l [9]

Figure 2. CVD-free lifetime gain (in years) from lowering systolic blood pressure by 10 mm Hg for apparently healthy persons at age 40–44 years, with systolic blood pressure 140–159 mm Hg by smoking status and non-HDL-cholesterol concentration [9]

CVD risk factors and COVID-19

The COVID-19 pandemic cost the world population over 5 ml deaths within two years, 2020 and 2021, and in Poland, in 2020, raised all-cause death rates by about 15%. It also decreased the attention to the prevention of CVD. However, soon after the outbreak of the pandemic, the reports on the characteristics of COVID-19 patients and especially on factors related to the severe or fatal outcomes of the disease included information on hypertension, diabetes, obesity, hypercholesterolemia, and CVD. The evidence was growing rapidly and before April 2021, Harrison et al. [63] identified 84 reviews on the relationship between COVID-19 and clinical characteristics. According to the AMSTAR 2 critical appraisal tool [64], most of them were classified as of low, or even of critically low quality. Only one was classified as a high-quality review and 31 as moderate quality reviews. Out of the latter 32 reviews, 23 included at least one meta-analysis on the relationship between COVID-19 and CVD or CVD risk factors [65–87]. The results of the meta-analyses are summarized in Tables 2 and 3. Even though some of the original reports were included in several meta-analyses, relative risk estimates varied, but mostly indicated significant, higher risk of serious course of the disease or death in COVID-19 patients with coexisting CVD and with hypertension and diabetes. Weaker homogenious results were obtained for smoking and obesity.

Table 2. Minimum and maximum estimates for the associations between cardiovascular disease or cardiovascular risk factors and mortality with COVID-19. Only moderate- or high-quality reviews included. Selection of reviews and classification according to the AMSTAR 2 criteria by Harrison et al. [63, 64]

Risk factor	Number of publications/number of meta-analyses	Statistically significant results	Minimum estimate	Maximum estimate	References
Smoking (current or former)	5/6	3	OR, 1.19 (95% CI, 0.48– 2.92)	OR, 2.24 (95% CI, 1.399–3.58)	65–69
Diabetes	14/16	15	OR, 1.33 (95% CI, 0.78–2.28)	RR, 3.34 (95% CI, 2.79–4.0)	65, 67, 68, 70–80
Hypertension	11/11	11	RR, 1.74 (95% CI, 1.31–2.30)	OR, 3.25 (95% CI, 2.15–4.91)	65, 67, 68, 71–75, 77, 79, 80
Obesity	2/2	1	RR, 2.18 (95% CI, 1.10–4.34)	OR, 2.28 (95% CI, 0.76–6.90)	67, 68
CVD	11/11	11	RR, 2.25 (95% CI, 1.60–3.17)	OR, 7.87 (95% CI, 2.12–28.57)	65 ,67, 68, 71–73, 75, 77, 79, 80, 82
MI	1/1	1	RR, 3.9 (95% CI, 1.5–8.6)		80
Cerebrovascular disease	8/8	6	RR, 2.16 (95% CI, 0.97–4.80)	OR, 5.84 (95% CI, 3.63–9.39)	65, 67, 68, 72, 73, 79, 80, 81

Abbreviations: CI, confidence interval; CVD, cardiovascular disease; MI, myocardial infarction; OR, odds ratio; RR, relative risk

Table 3. Minimum and maximum estimates for the associations between cardiovascular disease or cardiovascular risk factors and severe COVID-19. Only moderate- or high-quality reviews included. Selection of reviews and classification according to the AMSTAR 2 criteria by Harrison et al. [63, 64]

Risk factor	Number of publications /number of meta-analyses	Statistically significant results	Minimum estimate	Maximum estimate	References
Smoking (current of former)	6/17	8	RR, 0.72 (95% CI, 0.42–1.24)	OR, 3.05 (95% CI, 1.18–7.84)	66, 69, 72, 83–85
Diabetes	9/11	11	RR, 1.88 (95% CI, 1.10–3.23)	OR, 3.20 (95% CI, 2.26–4.53)	72, 75–77, 80, 83, 85–87
Hypertension	8/10	10	RR, 1.4 (95% CI, 1.1–1.7)	OR, 4.37 (95% CI, 2.99–6.39)	72, 75, 77, 80, 83, 85–87
Obesity	1/1	0	SMD, 1.27 (95% CI, 0.88–3.42)		85
CVD	9/11	11	RR, 2.1 (95% CI, 1.3–3.2)	OR, 5.12 (95% CI, 3.09–8.48)	72, 75, 77, 80, 82, 83, 85–87
MI	1/1	0	OR, 11.2 (95% CI, 0.44–285.9)		87
Cerebrovascular disease	4/45 [?]	4	RR, 1.9 (95% CI, 0.9–4.0)	OR, 5.73 (95% CI, 2.52–13.04)	72, 80, 85, 87

Abbreviations: SMD, standardized mean difference in BMI (severe disease vs. not severe disease); other — see Table 2

However, there is some concern about the figures presented in Tables 2 and 3. Many of the early studies which were included in the meta-analyses were done on small samples, frequently, the analysis was limited to the comparison of the prevalence of risk factors between those who developed severe disease or died from it and those who did not. One of such early reports was from Poland [88]. Such studies do not allow for more advanced statistical analysis which would control confounding factors like age, sex, and other important characteristics. For example, in one of the early reviews, only two out of 20 source studies reported adjustment for age [71]. Further, most of the early reports focused on patients in China where the pandemic began. Consequently, confounding by race and ethnicity was possible. For example, the effect of obesity could likely be underestimated in the lean Chinese population. The later studies, carried out in the European and American COVID-19 patients, which involved larger samples, confirmed a strong relationship between severe COVID-19 and age, but after adjustment for age, sex, and other covariates, did not confirm the relation between hypertension and fatal outcome or severe course of the disease. Results for diabetes, obesity, and hypercholesterolemia were heterogeneous. However, most of the more recent studies confirmed a relationship with cardiovascular disease, obesity, and diabetes, but not with hypercholesterolemia [63, 89–92].

In the recent, multivariable analysis of over 540 thousand adults with COVID-19, hospitalized in the United States, obesity contributed to a 13% higher risk of admission to an intensive care unit (ICU), a 50% higher risk of invasive mechanical ventilation, and a 30% higher risk of death. Diabetes with complications contributed to a 16% higher risk of ICU admission, a 42% higher risk of invasive mechanical ventilation, and a 26% higher risk of death. Coronary atherosclerosis or other heart disease was related to an 8% higher risk of ICU admission, a 10% higher risk of invasive mechanical ventilation, and a 14% higher risk of death. Diabetes with no complications, essential hypertension, and disorders of lipid metabolism were not related to an increased risk of death or severe course of the disease. Surprisingly, they indicated slightly (1%–9%) lower risk. However, essential hypertension increased the risk of death by 25% in the age group below 40 years. Accumulation of 10 conditions, out of which essential hypertension, dyslipidemia, obesity, and complicated diabetes were the most frequent, was related to the increased risk of ICU admission, invasive mechanical ventilation, and fatal outcome with a clear dose-related relationship [93].

Most studies on the relationship between CVD risk factors and COVID-19 were carried out in COVID-19 patients. Risk factors were mostly only a part of the studied characteristics, which were suspected to be related to serious outcomes of COVID. Less is known on the relationship between risk factors and the incidence of COVID-19. However, available information on obesity and diabetes supports the hypothesis that both are related to a higher risk of getting the disease. In the meta-analysis of 75 studies, obesity was related to a nearly 50% higher risk of being COVID-19 positive, over the two-fold risk of hospitalization for COVID-19, over 70% risk for ICU hospitalization, and nearly a 50% increase in the risk of death due to COVID-19 [94]. Observations made in the entire population of Scotland, at the first wave of the pandemic, indicated that, after adjustment for age and sex, about a 40% greater risk of fatal or critical ICU-treated COVID-19 was found in type 2 diabetes and over a twofold risk in type 1 diabetes as compared to the general population [95]. In a large French study, diabetes duration and BMI were predictors of hospitalizations for COVID-19 [96].

The statement of the World Health Organization (WHO) on the relationship between hypertension and COVID-19 underlines that available evidence suggests that hypertension increases the risk of severe COVID-19. However, the statement warns that it remains unclear whether this prognostic profile was independent of other risk factors, and there is not enough evidence whether people with hypertension, in comparison to otherwise healthy individuals, are at higher risk of being infected by SARS-CoV-2 [97]. Indeed, no results of systematic reviews or meta-analysis are available, which would elucidate whether people with hypertension or dyslipidemia, in comparison to healthy individuals, are at higher risk of SARS-CoV-2.

COVID-19 and atherosclerotic CVD

Most evidence on the impact of COVID-19 on cardiovascular health was collected for the acute phase of the disease. In general, as assessed in the meta-analysis of the studies, which involved over 77 thousand COVID-19 patients, the acute myocardial injury was present in 10% [98]. Among other described cardiovascular complications were incident arrhythmias, heart failure, cerebrovascular disease, incident venous thromboembolism, pulmonary embolism, and deep vein thrombosis. All of them were found to be associated with the fatal outcome of COVID-19 [63]. The longer perspective was taken in the extensive analysis of over 86 thousand patients matched with over 348 thousand controls in Sweden. In the first week after the exposure, the risk of MI and stroke was threefold higher; then it decreased and was 1.6 times higher (60% excess) for MI and twofold higher for stroke in weeks 3 and 4 [99]. The impact of COVID-19 on longer-term cardiovascular outcomes, in particular atherosclerotic CVD events, requires a follow-up longer than the history of the pandemic.

Conclusions

CVD and CVD risk factors, obesity, and diabetes in particular, are related to the severe course or fatal outcome of COVID-19. High prevalence of CVD risk factors with an increasing prevalence of obesity and diabetes could make the Polish population more sensitive to COVID-19 incidence and put infected persons at higher risk of serious complications and fatal outcomes of the disease. Therefore, it is likely that the increased number of CVD deaths observed during the pandemic could be partially explained by the high prevalence of CVD risk factors and atherosclerotic CVD, as well as by the direct cardiac complications of COVID-19, short-term higher risk of myocardial infarction and stroke, and possibly by the underuse of lifesaving procedures in an acute and chronic CVD.

Supplementary material

Supplementary material is available at https://journals.viamedica.pl/kardiologia_polska.

Article information

Acknowledgments: Authors express their gratitude to dr hab Jacek Jóźwiak, Professor of Opolski University, from the Department of Family Medicine of Collegium Medicum, for the advice on the presented results of the LIPIDOGRAM 2015 study and to Marlena Kostrzejowska, MS, Zuzanna Pazera, MS, and Agnieszka Matras, Lic., from the Department of Epidemiology and Population Studies of the Jagiellonian University Medical College, for their assistance in the preparation of the manuscript.

Conflict of interest: None declared.

Open access: This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially. For commercial use, please contact the journal office at kardiologiapolska@ptkardio.pl.

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