Prevalence of a combination of hypertension and dyslipidemia among the adult population of a large East Siberian region

Aim. To study the prevalence of a combination of two major cardiovascular risk factors, hypertension (HTN) and lipid metabolism disorders, among the Krasnoyarsk Krai population as a whole, as well as among men and women in different age groups. Material and methods. We analyzed the data from a random representative sample of 1603 residents of the Krasnoyarsk city and Berezovsky district aged 25-64 years within the ESSE-RF epidemiological study. Statistical processing was performed using IBM SPSS 22 and Microsoft Office Excel 2007. The proportion of people with hypertension and dyslipidemia and 95% confidence intervals was calculated. The significance of differences in the prevalence of hypertension and dyslipidemia was tested using the chi-squared test with Yates’ correction. Differences were considered significant at p≤0,05. Results. The prevalence of a combination of HTN and any dyslipidemia was 40%, HTN + hypercholesterolemia — 31,6%, HTN + high low density lipoprotein cholesterol (LDL-C) — 32,3%, HTN + hypertriglyceridemia — 16,4%, HTN + reduced high density lipoprotein cholesterol (HDL-C) — 10,8%. This characteristic increased with age. The prevalence of a combination of HTN with hypercholesterolemia, with an increased LDL-C level, as well as HTN with any dyslipidemia in women aged 55-64 years was significantly higher than in men. Conclusion. The prevalence of a combination of HTN with any dyslipidemia in the Krasnoyarsk Krai among the adult population aged 25-64 years was 40% and increased with age. In women aged 55-64 years, the prevalence of a combination of HTN with hypercholesterolemia, with an increased LDL-C level, as well as HTN with any dyslipidemia was significantly higher than in men.


Introduction
Epidemiology statistics indicate that >90% of hypertensive (HTN) patients in North America, Europe and the Middle East and >80% in Australia, Latin America and Asia have at least one additional cardiovascular risk factor [1]. In particular, the pre valence of dyslipidemia (DLP) among persons with HTN is ~1,21,5 times higher than in the general popu lation [25].
In medical literature, the term dyslipidemic hypertension first appeared in the context of familial DLP [6], although later it received a broader inter pretation. Dalal JJ, et al. (2012) proposed the term lipitension to denote the simultaneous presence of HTN and DLP and reported the need for "active identification, diagnosis, and management of these two risk factors together, as global cardiovascular risk factors" [7].
To date, a sufficient amount of epidemiological data has been accumulated in favor of the fact that the combination of HTN and lipid metabolism disorders not only sums up the risk of unfavorable cardiovascular outcomes (primarily of an atherosclerotic nature), but can also multiply this risk by 23 or more times. This is confirmed by a number of wellknown works, such as the Framingham study [8], the Multiple Risk Factor Intervention Trial (MRFIT) [9], and the Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (INTERHEART) study [10]. The average prevalence of a combination of HTN and DLP in the general population is 15 31%, while significant differences are found depending on age, sex (in young and middle age, it is more often recorded among men), ethnicity (less often in Spaniards, more often among African Americans) [7,1113].
It should be emphasized that, in contrast to epidemiological observational studies, not all lipid metabolism parameters demonstrated their significant causal relationship with the development of atherosclerotic cardiovascular diseases, primarily coronary artery disease, when using such a sensitive genetic approach as the Mendelian randomization (MR). Thus, the last largescale study by Zanetti D, parameters were evaluated. By enzymatic methods on an Abbot Architect c8000 Clinical Chemistry Analyzer using Abbot Diagnostic (USA) kits, the following lipid profile parameters were studied: total cholesterol (TC), LDLC, HDLC and TG. Hypercholesterolemia (HC) was diagnosed with total cholesterol ≥5,0 mmol/L. The increased LDLC and TG levels were ≥3 mmol/L and ≥1,7 mmol/L, respectively, while a decrease in the HDLC level was recorded at <1,0 mmol/L and <1,2 mmol/L in men and women, respectively.
Statistical processing was carried out in the programs IBM SPSS 22 and Microsoft Office Excel 2007. The proportion of those with HTN and DLP among the total number of participants and 95% confidence intervals (CI) was calculated. The significance of differences between the groups was tested using the chisquared test with Yates' correction. Differences were considered significant at p≤0,05.

Results
The study included 652 (39,4%) men and 951 (60,6%) women. The combination of HTN and any DLP was observed in 40% (37,6%; 42,5%) of participants. At the same time, with an increase in age, there is a natural and significant increase in the prevalence of lipitension both in the general population (from 10,7% in patients aged 2534 years to 66,6% in those aged 5564 years) and among women (Table 1). In men, the studied indicator reaches a plateau in the 4554 age group. There was also a tendency towards a lower prevalence of lipitension among women compared with men aged 2554 years, with the exception of a significant increase in the 5564 age group (72,5 vs 58,1%).
The prevalence of different variants of HTN + DLP combination, depending on sex and age, is shown in Figure 1.
The combination of HTN and increased LDLC levels have the similar characteristics ( Figure 1B). et al. (2020) using MR techniques showed the patho genetic role of lowdensity lipoprotein cholesterol (LDLC), triglycerides (TG), lipoprotein(a) and apoli poprotein B. However, as before, the role of high density lipoprotein cholesterol (HDLC) was not confirmed, which, according to the authors, is a simple biochemical marker rather than a true risk factor [14].
The same MR approach using metaregression analysis has shown that a longterm (lifelong) genetic decrease in both LDLC and systolic blood pressure (BP), and to an even greater extent, their combination, lead to a significant decrease in cardiovascular risk [15]. Moreover, the first data appeared in favor of the fact that there may be a causal relationship between the LDLC level and HN [16]. It is not surprising that the European Atherosclerosis Society experts, among all lipid metabolism parameters, recognize LDL as the most important, "primary driver of atherogenesis" [17,18].
Since the discussion of combined antihypertensive and lipidlowering therapy seems logical in the presence of HTN and DLP combination, it is extremely important to reveal the actual prevalence of lipitension in the population of one of the largest Russian regions. In this regard, the aim of the study was to investigate the prevalence of a combination of two major cardiovascular risk factors (HTN and lipid metabolism disorders) among the Krasnoyarsk Krai population as a whole, as well as among men and women in different age groups.

Material and methods
The work was carried out within the ESSERF epidemiological study [19] on a random representative sample of 1603 residents of the Krasnoyarsk and Berezovsky rural district of Krasnoyarsk Krai aged 2564 years. This study was performed in accordance with the Helsinki declaration. The medical ethics committee approved this study. All patients signed informed consent.
A questionnaire was drawn up for each participant. Blood pressure was measured twice on the right arm with a 5minute interval in a sitting position. Fasted blood samples were taken from the ulnar vein. Hypertension was considered as the systolic BP ≥140 and/or diastolic BP ≥90 mm Hg or BP >140/90 mm Hg with a receiving antihypertensive therapy.
Venous blood samples were centrifuged, serum was frozen and delivered to the federal center, where biochemical 25 to 64 years old and practically equals with men aged 5564 years. Finally, the combination of HTN with a reduced HDLC levels is observed in 10,8% (9,3%; 12,4%) in the general population. It tends to grow up to the 45 54 age group (from 4,1 to 14,8%), and at an older age does not change significantly ( Figure 1D). At the same time, sex differences in any of the age groups were not significant.
It is noteworthy that the prevalence of individual DLP markers differs in persons with HTN and those with a normal BP level. So, in hypertensive patients, an increased LDLC and HTG levels are more often recorded in the 2534 and 3564 age groups, respectively, while a decreased HDLC level at the age The prevalence of this variant of lipitension in general population is 32,3% (29,3%; 34,0%) and naturally increases with age from 7,9 to 54,7%. In addition, if at the age of 2534 years, the HTN + increased LDLC combination is more common among men (12,3 vs 4,8%), then in the older age group of 5564 yearsamong women (66,3 vs 38,0%).
The combination of HTN + hypertriglyceridemia (HTG) is recorded in the general population relatively less often -in 16,4% (14,6%; 18,3%), but also steadily increases with age -from 2,5 to 28,6% ( Figure 1C). In men, this indicator reaches a plateau at the age of 4554 years and exceeds this in women in the age range of 25 54 years. In women, in contrast to men, the prevalence of HTN + HTG combination is steadily increasing from . Notes: А) Age differences are significant (p<0,001). Sex differences are significant only in the 5564 age group (p<0,001), but insignificant in other age groups. В) Age differences are significant (p<0,001). Sex differences are significant in the 2534 (p=0,011) and 5564 age groups (p<0,001). С) Age differences are significant (p<0,001). Sex differences are significant in the 3544 and 4554 age groups (p<0,001). D) Age differences are significant (p<0,001). Sex differences are not significant in any of the age groups. differences are either insignificant, or there is a slight superiority towards men, but at an older age, these combinations are much more common in women.
The most logical (but not the only) explanation for such dynamics is the cardioprotective profile of female sex hormones in reproductive age and testo steroneestrogen imbalance during and after meno pause [22,23].
The combination of HTN + HTG and HTN + low HDLC in the Krasnoyarsk Krai population tend to prevail among men aged 2554 years, and then level out in men and women in the 5564 age group. The listed features are generally comparable with the average Russian data according to the ESSERF study [2], except that the HTN + low HDLC combination within the general Russian population continues to be more often recorded in men compared with women and in the older age group (5564 years old).
Unfortunately, dietary changes and adequate exercise, being important components of the car diovascular prevention, are still inferior to active drug therapy in their ability to improve the prognosis with of 2534 and 4554 years old. There were no significant differences in the increased total cholesterol level ( Figure 2).

Discussion
Thus, in the Krasnoyarsk Krai, not only HTN (49,4%) [20] has a high prevalence, but also its com bination with DLP, which, according to study results, was 40%. This indicator was higher than in the US epidemiological studies (1531%) [1113], but lower than in Lithuania [5].
The combination of HTN with the most important parameter of lipid metabolism disorders (increased LDLC) is recorded in 1/3 of the adult population, in ~40% of people aged 4554 years and in more than half of the Krasnoyarsk Krai population aged 5564 years old. This combination is comparable in its prevalence to the United States [12], but lower in comparison with the Lithuanian [5] and Malaysian populations [21].
The prevalence of two types of lipitension (HTN + elevated total cholesterol and HTN + elevated LDLC) increases with age. Moreover, at a young age, sex   [25]. Therefore, with the combination of hypertension and DLP, it seems logical to prescribe combined antihypertensive and lipidlowering therapy, primarily statins. Evidence of this approach is provided by a number of randomized controlled trials, as well as two large metaanalyzes [26,27], which demonstrated an improvement in longterm cardiovascular prognosis in such patients (with an additional 21% risk reduction compared with antihypertensive therapy only). The tactics with early initiation of not only antihypertensive, but also lipidlowering therapy is supported by the metaanalysis with 327037 participants [28]. In addition, the use of fixeddose combinations of statins and antihypertensive drugs in patients with lipitension contributes to an increase in medical adherence in actual clinical practice and a significant improvement in clinical outcomes, as evidenced by the recently published metaanalysis by Weisser B, et al. [29].

Conclusion
The prevalence of a combination of HTN with any DLP type in the Krasnoyarsk Krai among the adult population of 2564 years is 40% and increases with age. The combination of HTN with the most important parameter of lipid metabolism disorders (increased LDLC) is recorded in 1/3 of the adult population (32,3%), in ~40% of those aged 4554 years and in more than half of the population aged 5564 years. A combination of HTN and an increased total cholesterol level has similar statistics. In men, the prevalence of HTN and both elevated LDLC and total cholesterol levels gradually increasing, reaches its plateau in the 4554 age group. In women, compared with men, the combination of HTN with an increased level of LDLC and total cholesterol is less common at a younger age, leveled out in the 4554 age group, and prevails in the 5564 age range. In order to effectively reduce the burden of HTN and hyperlipidemia, a wider and earlier introduction of combined antihypertensive and lipidlowering therapy (primarily statins) should be considered.