Introduction:
In many developed countries demographic picture indicates growth of older people population. According to definition of the European Regional Office, biological senile age is 75-90 years and, in turn, senility is considered as a decrease in adaptive abilities of a human body [1]. Recent large-scale studies demonstrate that cardiovascular diseases are still predominant in men and women above 80 years old. Despite several alterations of morbidity and mortality structure, cardiovascular events are basic causes of lethality (i.e. 30% of total mortality) [2].
It is commonly known that, due to longer life, women represent a predominant part of a sample. In 2017 the Federal State Statistics Service reported that life duration was 77.06 and 66.5 years in women and men, respectively, in the Russian Federation [3]. As compared with males, number of females is 1.157 times higher in Russia. As for persons above 80 years old, the value is even 3.041 times higher. As biological differences between men and women is in little doubt, the factor plays a key role in development and course of cardiovascular diseases (CVD). According to multiple researches, prevalence of myocardial infarction (MI) and heart failure is higher in men than in women [4]. Therefore, it's a little wonder if, despite comparably lower level of other cardiovascular risk factors, an estimated cardiovascular risk is higher than 5-10% in senile men. Hypertension, dyslipidemia and heart failure are primary predictors of cardiovascular mortality.
Considering data mentioned above, the purpose of the research is to study gender aspects of cardiovascular system functional status in senile patients (SP).
Materials and Methods:
Seventy four senile patients (32 males and 42 females) aged 75-90 years old were examined in an outpatient department. To be enrolled in the study, patients underwent a combined clinical laboratory examination, electrocardiography (ECG) and daily blood pressure monitoring (DBPM). Actual biological age (ABA) was determined according to blood parameters (i.e., monocytes (M), total protein (TP), urea (U1), creatinine (C) and erythrocyte sedimentation rate (ESR)). ABA (i.e., one of available hemodynamic ageing markers) was calculated using the formula: ABA= 91.1512 - 1.17 x M + 0.5683 x ESR - 0.4346 x TP + 2.2088 x U1 - 0.6613 x C [5]. Electrocardiography was performed as per the standard method by PHILIPS-HD3 apparatus (Japan). End-systolic dimension (ESD, mm), end-diastolic dimension (EDD, mm), end-systolic and end-diastolic volumes (ESV and EDV, ml), left ventricular myocardium posterior wall thickness (LVPWT, mm) and interventricular septum thickness (IST, mm), A-P dimension of the left atrium (LA, mm) and ascending aortic diameter (AAOD, mm) were measured. LV hemodynamic load was assessed in virtue of load index volume (LIV) calculated as per the formula: LIV = EDV/LVMM (ml/g) and atrioventricular ratio (AVR): AVR = LA/EDD. LV myocardial efficiency was calculated on basis of LV ejection fraction (EF) and systolic ejection rate (SER, ml/g/m2): SER=SO/LVMM. Nature of LV remodelling was evaluated in virtue of the left ventricular myocardial mass index (LVMMI) and LV wall relative thickness index (RTI). RTI<0.45 and MMI≤N meant normal geometry (NLVG); RTI≥0.45 and MMI≤N demonstrated concentric remodelling (LVCR); RTI≥0.45 and MMI>N indicated concentric LV hypertrophy (CLVH); MMI>N and RTI<0.45 demonstrated eccentric hypertrophy (ELVH) [6].
To assess functional aspects of cardiovascular system (CVS), sports medicine-related hemodynamic estimates were used. CVS adaptative potential (AP) was determined using R.M. Baevskii estimated index [7]: AP = (0.0011 x HR) + (0.014 x SBP) + (0.008 x DBP) + (0.009 x BW) - (0.009 x H) + (0,014 x A) - 0.27, where HR - heart rate (beats/min), SBP - systolic blood pressure (mm Hg), DBP - diastolic blood pressure (mm Hg), H - height (cm), BW - body weight (kg), A - age (years). <2.6 scores meant satisfactory adaptation; 2.6-3.09 scores - adaptative mechanism effort; 3.09-3.4 scores - unsatisfactory adaptation; >3.5 scores - adaptation failure. Output (systolic) volume was calculated using Starr's formula: SV = 90.97 + 0.54 x PP - 0.57 x DBP - 0.61 x A, where SV - systolic (output) volume (ml), PP - pulse pressure (mm Hg). Cardiac output (CO) was calculated using the formula: CO = SV x HR. To assess BP orthostatic reaction, BP and HR were measured after 10-min rest in a recumbent position, as well as in 1, 2 and 3 min after standing in an upright position. If a recumbent position changed to an upright one induced decrease in BP (i.e., by ≥20/10 mm Hg), orthostatic hypotension was diagnosed [8]. Several integral indicators (i.e., Hildebrandt index (HI) and Kerdo autonomic index (KAI)) were used to determine a predominant type of autonomic regulation [9]. Based on pulse and diastolic pressure values, the index was calculated using the formula: KAI = (1 - DBP/HR) x 100. Negative Kerdo index indicated predominant vagotony. This means more favorable anabolic type of metabolism with prevalent inhibitory processes in ANS activity (i.e., an efficient functioning). Positive KAI meant strained ANS functioning, predominant catabolism and increased consumption of body reserves.
HI was calculated using the formula: HI = HR/RR, where RR - respiration rate (per min). 2.8-4.9 range was considered as a vegetative balance; >4.9 and <2.8 values demonstrated sympathicotonia and vagotony, respectively. Endurance coefficient (EC) (i.e., an addition to evaluation of cardiovascular system functional status) was calculated as per A. Kvaas formula: EC=HR/PP [10]. EC values >1.6 and <1.6 indicated weakened and enhanced functional status of CVS, respectively. Hemodynamics efficiency was assessed on basis of circulation efficiency coefficient (CEC) representing a volume-frequency ratio of pressure level difference and HR: CEC = (SBP - DBP) x HR [11]. Increased CEC value (>2600 conventional units) indicated strained ergonomics of CVS. Physical state level (PSL) was calculated using the formula: PSL = (700 - 3 x HR - 2.5 x mean BP - 2.7 x A + 0.28 + BW)/ 350 - 2.6 - A + 0.21 x H, where mean BP = (2xDBP + SBP)/3.
Moreover, to detect long-livers (i.e., persons above 90 years old) in a patient's genealogical table, all the subjects underwent a genealogical anamnesis. All the patients were divided according to a gender. Statistical processing was performed using Microsoft Excel 7.0 and Statistica for Windows 10.0 software. Standard parametric and nonparametric methods of descriptive statistics were applied. Correlation between parameters was determined by a nonparametric Spearman coefficient. 0.05 was considered as a null hypothesis disallowance critical level.
Results and Discussion
According to the results, mean chronological age of enrolled subjects was 81.9±5.2 years. In the setting of natural physiological ageing, stated age (SA) typically coincides with a biological one (BA) (i.e., body status degree). However, AA (83.7±5.3 years) was higher than SA (81.2±4.8 years; p<0.05) in senile men. This indicates not only a presence of more significant age-related factor of a cardiovascular risk but also predominant signs of accelerated ageing. In spite of less occurrent genetically determined long living in the group (42.9% vs. 53.1%; p<0.05), SA (82.3±4.6 years) was slightly lower than AA (80.7±4.4 years; p<0.05) in women. Arrhythmia, cerebrovascular disease, left ventricular hypertrophy, myocardial infarction, chronic obstructive lung disease and obliterating atherosclerosis were more common in men. Although lower limb varicose veins was more occurrent in women, it did not meet criteria of statistically significant intergroup differences. Diabetes mellitus and ischemic heart disease were equally occurrent (see Table 1).
| Table 1:
Comparative analysis of senile subjects |
Parameters |
Males
(n=32) |
Females
(n=42) |
Mean stated age, years |
81.2±4.8 |
82.3±4.6 |
Mean actual age, years |
83.7±5.3 |
80.7±4.4* |
First-branch long-lived relatives, % |
53.1 |
42.9* |
BMI, kg/m2 |
24.4 ± 4.2 |
27.4±6.2 |
History of hypertension, % |
100 |
100 |
Hypertension (I degree), % |
43.8 |
47.6 |
Hypertension (II degree), % |
46.9 |
42.9 |
Hypertension (III degree), % |
9.3 |
9.5 |
Isolated systolic hypertension, % |
12.5 |
19.1* |
Hypertension duration, years |
9.7±5.9 |
15.3±6.1* |
Orthostatic hypotension, % |
31.3 |
19.1 |
Acute cerebrovascular accident, % |
31.3 |
11.9* |
Arrhythmia, % |
59.4 |
35.7* |
Postinfarction cardiosclerosis, % |
43.8 |
28.6* |
IHD, % |
78.1 |
76.2 |
COPD, % |
34.4 |
26.2 |
Diabetes mellitus, % |
21.9 |
23.8 |
Varicosity, % |
59.4 |
69.1 |
Obliterating atherosclerosis, % |
46.9 |
14.3* |
Prostate adenoma, % |
53.1 |
- |
| Note: * p<0.05. |
Evaluating BP values, it is worth noting that mean daily SBP was higher in men (141.8±13.3 mm Hg) than in women (139.5±14.9 mm Hg). However, both mean daily and office diastolic BP values were higher in women (72.7±7.6/78.2±6.4 mm Hg vs. 67.4±8.5/69.3±7.7 mm Hg). Moreover, females demonstrated longer hypertension (15.3±6.1 years) and higher incidence of isolated systolic hypertension (19.1%). Short-term hypertension is associated with parallel measurement of SBP and DBP. Nevertheless, longer duration shows initially stabilized and, then, decreased DBP values together with increasing SBP. That's why, a substantial PP difference whose significance is associated with vascular stiffness, increased SO and reflection wave amplitude is observed in senile patients. Results of the mentioned study confirm that PP and PVR increase and, in turn, SV and CO decrease simultaneously in an age-related manner. Excessive PP values detected both in men and women indicate maintenance of very high CVR (see Table 2). At the same time, the peak PP value was significantly higher (i.e., by 15.7% (p<0.05)) in men. This may be responsible for high incidence of cerebrovascular disease, stroke or discirculatory encephalopathy in their medical histories (31.3% vs. 11.9%).
| Table 2: Main hemodynamic and biochemical parameters in senile patients |
| Parameters |
Males (n=32) |
Females (n=42) |
Office SBP, mm Hg |
142.1±15.8 (115-160) |
138.8±12.5 (108-152) |
Office DBP, mm Hg |
68.8±9.7 (54-77) |
79.2±6.4 (65-86) * |
HR (ECG), bpm |
69.7±6.1 (50-79) |
75.2±9.4 (55-86) * |
Daily SBP, mm Hg |
140.8±13.3 (110-162) |
139.5±14.9 (109-166) |
Daily DBP, mm Hg |
67.4±8.5 (56-74) |
74.7±7.6 (60-82) |
Daily HR, bpm |
70.9±6.2 (49-82) |
75.4±8.4 (58-95) * |
Daily PP, mm Hg |
75.2±8.2 (64-82) |
63.4±5.9 (54-73) * |
SBP, mean daily variability |
15.2±4.7 (12-18) |
12.1±4.4 (9-17) |
DBP, mean daily variability |
10.5±2.3 (8-15) |
9.6±2.2 (8-12) |
SV, ml |
43.3±5.1 (36-55) |
34.8±4.7 (28-45) * |
CO, ml |
3109.5±186.8 (2880-3995) |
2788.2±144.3 (2240- 3150) * |
Glucose, mmol/l |
5.02±0.4 (3.4-7.8) |
5.5±0.7 (3.6-7.2) |
Creatinine, μmol/l |
119.6±17.9(65.2-132.6) |
124.1±19.7(60.6-140.8) |
Total cholesterol, mmol/l |
4.4±0.8 (3.6-5.2) |
5.2±0.4 (3.8-5.9) |
GFR, ml/min/1.73m2 |
46.3±4.2 (40.8-58.6) |
43.2±5.5 (39.6-62.6) |
| Note: * p<0.05. Data are presented as a median (25th and 75th percentile). |
Complementary to hypertension, orthostatic hypotension (OH) (i.e., an independent risk factor of cardiovascular complications, asthenization and mortality) is an important feature of SP [12]. OH is associated with worse quality of life, increased risk of falling, fractures and cognitive disorders. According to TILDA findings, orthostatic hypotension is observed in 18.5% of persons above 80 years old. At the same time, the value is 3 times lower in overall population [13]. The study demonstrated OH detected in 18 of 74 patients. Moreover, it was more occurrent in men (31.3%) with history of peripheral vascular atherosclerosis. So, the fact confirms importance of high PP value and lower extremity artery atherosclerosis in OH genesis. Benvenuto L.J. et al. obtained similar results. Namely, patients with hypertension and peripheral lower extremity artery atherosclerosis demonstrated high incidence of orthostatic hypotension [14]. Although for a long time they considered that antihypertensive therapy can aggravate hypotension and increase falling risk in senile persons, current data do not confirm the point of view. SP with poorly controlled hypertension and OH have higher cardiovascular risk than those who receive hypotensive therapy [15].
Analyzing HR values, it is worth noting that males demonstrated lower number of heart beats than females (p<0.05). This indicates predominant hypokinetic circulation associated with increased specific peripheral resistance and decreased senile age.
According to curious findings of Japanese researchers, male heart rate < 60 or > 80 bpm is an independent predictor of mortality that substantially (i.e., by 50%) decreases survival rate in senile men under 85 years old [16]. Since there is no a clear connection between high pulse rate and CVD-induced mortality in middle-aged women, they are substantially more likely to live up to senility. Female ageing may be accompanied by less evident functional strain of CVS that depends on dynamic balance between parasympathetic and sympathetic nervous system. Therefore, evaluation of autonomic nervous system was of special interest.
It is pretty expected that, due to altered autonomic status in the setting of chronic diseases and very dynamic physiological impact of outer environmental factors (e.g., meteorological and climatic ones), detection of ANS features is quite complicated in SP. Considering the fact that an autonomic status of an SP can be hardly evaluated as a result of a single assessment of ANS function, Hildebrandt index and Kerdo autonomic index (see Table 3) were used as criteria to record relatively small changes in autonomic activity.
| Table 3: Comparative analysis of CVS functional status parameters in senile patients |
| Parameters |
Males
(n=32) |
Females
(n=42) |
Kerdo index |
6.2±4.5 |
-0.9±3.3* |
Hildebrand index |
4.8±0.7 |
3.7±0.8* |
CEC |
4992.6±469.8 |
4451.3±358.7 |
EC |
0.98±0.04 |
1.19±0.05 |
PSL
low, %
below average, %
average, %
above average, %
high, % |
0.385 ± 0.24
25.0 (0.225-0.375)
43.8 (0.376-0.525)
28.1 (0.526-0.675)
3.1 (0.676-0.825)
0 (0.826 ≥) |
0.291 ± 0.19
23.8 (0.157-0.260)
40.5 (0.261-0.365)
28.6 (0.366-0.475)
7.1 (0.476-0.575)
0 (0.576 ≥) |
AP, score
Satisfactory AP, %
Adaptative mechanism effort
Unsatisfactory AP, %
Adaptation failure, % |
3.12±0.08
18.8
31.3
37.5
12.5 |
2.84±0.09*
28.6
47.6
19.0
4.8 |
| Note: *p<0.05 |
According to KAI analysis, most patients demonstrate a clear trend to increased impact of ANS sympathetic tone. Mainly, sympathetic tone prevailed in males (KI=6.2±4.5; HI=4.8±0.7). Although females demonstrated all the types, greater tendency to eutonia or parasympathetic type (KI= -0.9±3.3; HI=3.7±0.8) was observed indicating efficient functioning of CVS and greater adaptive-compensatory ability of female population. Evaluation of cardiovascular system adaptation level in senile patients using R.M. Baevskii estimated index was of importance. According to the findings, male population demonstrated equivalent incidence of unsatisfactory CVS adaptation (37.5%) and adaptative mechanism effort (31.3%). This meant decreased reserve functional capabilities of a senile patient (mean group score is 3.12±0.08). Females, in turn, showed prevalent adaptative mechanism effort (47.6%). This confirmed shift of equilibrium of regulatory systems associated with a safe functional reserve (mean group score is 2.84±0.09). CEC and EC estimates that enabled additional detection of gender aspects of systemic hemodynamics supported great adaptive abilities of senile females. Along with this, both groups showed below average physical state (i.e., 0.385 ± 0.24 and 0.291 ± 0.19 in men and women, respectively). The findings allow for the conclusion that despite gender differences of functional abilities, senile patients can adapt in new age ranges. It is expected that decreased adaptivity and reserve of CVS is associated with more significant disorders of systemic hemodynamic parameters in males. Thus, comparative analysis of echocardiographic parameters was performed in senile patients.
It is found that most enrolled subjects have increased LVMM and its index. Senile males demonstrated more evident signs of abnormal heart remodelling (i.e., significantly large values of AAOD, LA and IST). As per reported data, ageing of a hypertensive senile man is associated with enhanced diastolic disorders, as well as LVMMI and RTI increased by 1.78 g/m2 and 0.2 units, respectively, annually [17]. As compared with females, LV ejection fraction was by 6.9% lower in males (p=0.024) in spite of safe myocardial contractile function. SER (i.e., an estimate representing functional status and performance efficiency of myocardium) indicated myocardial contractile function disorders. SER activity was by 7.7% lower in men than in women (0.39±0.02 ml/g vs. 0.42±0.01 mg/g, respectively). It is important to note a determined inverse relationship between myocardial performance efficiency (SER) and SBP value (r= -0.50; p=0.04) in males. Therefore, a relationship between adaptive-compensatory changes and hemodynamic load leading to structural geometrical change of left ventricle myocardium architectonics becomes apparent.
SP included in study groups were not divided according to LV remodelling types (p>0.05). Mainly, concentric remodelling was observed. In particular, women and men demonstrated CLVH and LVCR (38.1% vs. 37.5%, respectively). It is known that LV concentric remodelling is an initial adaptation to increased afterload. In case of inadequate hemodynamic load, it gives way to concentric hypertrophy resulting in formation of morphofunctional and structural geometrical features of myocardium in hypertensive patients regardless of age and sex. Short-term hypertension and hypokinetic circulation may result in concentric heart remodelling which is more favorable in terms of prognosis prevailing in males with altered intracardiac hemodynamic parameters.
Comparative analysis of plasma biochemical parameters was of special interest. Despite absence of significant intergroup differences, mean total cholesterol and glucose levels were lower in males than in females (see Table 2). Increased blood creatinine level led to lower glomerular filtration rate (GFR) in males (46.3±4.2 ml/min/1.73 m2) and females (43.2±5.5 ml/min/1.73 m2) (p<0.05). The fact confirmed functional renal failure which had a physiological cause. Ageing results in decreased number of active nephrons, as well as lower blood flow velocity and renin activity. In turn, this resulted in age-related specific development of hypertension and CHF in senile persons. Finally, we would like to mention high prevalence of hypocholesterolemia associated with high incidence of oncological diseases (including malignant neoplasms [18]) in persons above 80 years old. However, the issue was not covered by the study.
Conclusions:
Ageing is a natural irreversible process which is inherent to each living body. Individual ageing rate depends on adaptative genetic capabilities. Certainly, this should be considered in dealing with such a specific category of patients.
Based on our findings, we can draw a conclusion about gender-specific differences between functional abilities of senile patients who can adapt, adjust themselves and function regardless of their age. Increased biological age detected in males indicated more significant impact of an age-related factor. Men demonstrated greater SBP and DBP values, as well as high incidence of orthostatic hypotension. Senile males showed more evident signs of abnormal heart remodelling (i.e., significantly large values of AAOD, LA and IST; worse myocardial activity). CEC, EC and Baevskii index values indicated greater adaptative abilities of senile females.
Involutory changes of an entire body have a particular contribution in systemic hemodynamics. This should be considered by an attending physician selecting an appropriate drug. The primary goal is a patient-specific approach to maintain working capacity of a senile body and to delay age-related processes.
New data on ageing mechanisms are of great importance for development of a concept of impact on life duration and active longevity prolongation.
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