Cardiorenal relationships and quality of life in elderly patients with arterial hypertension during therapy with lisinopril and indapamide

The dissertation is devoted to the study of cardiorenal relationships and quality-of-life indicators in elderly patients with arterial hypertension, as well as to the evaluation of the effects of lisinopril and indapamide monotherapy on the 24-hour blood pressure profile, morphofunctional parameters of the heart, central hemodynamics, heart rate variability, functional state of the kidneys, biochemical parameters, quality of life, and cognitive-mnestic functions. The work is aimed at the early diagnosis of disorders of glomerular and tubular renal function, the analysis of interrelations between cardiovascular and renal parameters, and the optimization of the choice of antihypertensive therapy in elderly patients, including those with isolated systolic and systolic-diastolic arterial hypertension.

The practical significance of the research is associated with the revealed nephroprotective effect of lisinopril and indapamide, as well as with the implementation of the obtained results into the clinical practice of therapeutic and cardiological departments of healthcare institutions in Volgograd and into the educational process of Volgograd State Medical University.

General demographic trends in the world are determined by the transition from a society with high birth rate and high mortality to a society with low birth rate and increasing life expectancy [239]. Data from the All-Russian Population Census indicate an increase in the average age of the population of our country: the proportion of people older than 60 years is 18.5%, older than 80 years — 1.8% [68], which naturally affects the prevalence of arterial hypertension (AH). Elevated blood pressure (BP) is detected in more than 50% of men and women older than 60 years and in 66% of those older than 70 years [112]. According to the Epidemiological Survey of Patients in the European Part of Russia (EPOChA, 2003), among persons older than 50 years, the number of effectively treated AH patients out of the total number of those taking medications does not exceed 15%, and the number of patients whose BP is pharmacologically controlled at the target level is 2.7% [117].

The share of AH in the formation of hypertensive nephrosclerosis and end-stage renal failure has not only not decreased but has shown a clearly discernible tendency to increase [33, 141, 202]. In the United States, within the next 10 years the number of patients requiring renal replacement therapy is expected to double and exceed 2 million people [218, 252]. In Russia, the annual increase in the number of patients receiving renal replacement therapy is 8.68% [85]. According to data of I.A. Borisov and V.V. Sura (2000), the incidence of chronic renal failure (CRF) is substantially higher in elderly and senile patients [16].

At present it is well known that not only a cardiovascular but also a renal continuum exists [93]. Hypertensive nephropathy leads not only to the development of CRF but also substantially accelerates the progression of the disease itself, increasing the risk of death from heart failure and other cardiovascular complications [72]. The results of numerous studies and the analysis of existing registries of patients with renal pathology clearly indicate that the frequency of cardiovascular complications and mortality from them in such patients is much higher than in the general population [148, 250, 257, 308]. In this connection, the search for markers that reliably describe disorders of cardiorenal relationships and their dynamics under the relevant treatment modalities becomes particularly relevant [90].

To date, there are virtually no publications on intraglomerular hemodynamics and tubular function of the kidneys in elderly patients with AH. The available medical literature insufficiently covers issues devoted to the study of cardiorenal relationships in elderly patients with AH. The cardiorenal aspects of prescribing angiotensin-converting enzyme inhibitors and diuretics in this category of patients remain poorly studied.

Quality of life (QoL) is a generally accepted criterion of the long-term effectiveness of antihypertensive therapy. The assessment of the dynamics of QoL parameters during treatment is an important aspect of therapeutic strategy in relation to elderly patients, in whom a decrease in cognitive functions and social adaptation is observed not only due to the presence of the disease but also as a result of age-related changes [55].

Aim of the study

The aim of the study is the early diagnosis of disorders of the functional state of the kidneys, the investigation of cardiorenal relationships and quality of life in elderly patients with arterial hypertension, as well as the optimization of therapy in this category of patients.

Main tasks of the study

1. To perform a comprehensive study of the state of glomerular and tubular function of the kidneys in elderly patients with AH.

2. To analyze the frequency of disorders of the functional state of the kidneys in elderly patients with AH and to compare these data with indicators in the group of middle-aged hypertensive patients and in elderly persons without clinically significant cardiovascular pathology.

3. To study the features of ambulatory blood pressure monitoring (ABPM) parameters, morphofunctional parameters of the heart, central hemodynamics, heart rate variability (HRV), indicators of lipid, purine, carbohydrate and electrolyte metabolism, parameters of QoL and cognitive-mnestic functions in elderly patients with AH.

4. To study cardiorenal relationships in elderly patients with AH.

5. To evaluate the effect of lisinopril monotherapy on ABPM parameters, morphofunctional parameters of the heart and central hemodynamics, HRV, functional state of the kidneys, biochemical parameters, QoL and cognitive-mnestic functions, taking into account the features of cardiorenal relationships in elderly patients with AH.

6. To evaluate the effect of indapamide monotherapy on ABPM parameters, morphofunctional parameters of the heart and central hemodynamics, HRV, functional state of the kidneys, biochemical parameters, QoL and cognitive-mnestic functions, taking into account the features of cardiorenal relationships in elderly patients with AH.

Scientific novelty

1. For the first time, a comprehensive comparative assessment of glomerular and tubular function of the kidneys has been performed in elderly patients with AH.

2. For the first time, the features of ABPM parameters, morphofunctional parameters of the heart and central hemodynamics, HRV, indicators of lipid, purine, carbohydrate and electrolyte metabolism have been studied in their interrelationship with the functional state of the kidneys in elderly patients with AH.

3. For the first time, the features of QoL and cognitive-mnestic functions in their interrelationship with the functional state of the kidneys in elderly patients with AH have been studied.

4. For the first time, a comprehensive assessment has been performed of the effect of lisinopril and indapamide monotherapy on ABPM parameters, morphofunctional parameters of the heart and central hemodynamics, HRV, functional state of the kidneys, biochemical parameters, QoL and cognitive-mnestic functions, taking into account the features of cardiorenal relationships in elderly patients with AH.

Scientific and practical significance of the work and implementation of its results

The study points to the importance of identifying early signs of renal damage in elderly patients with AH (decrease in glomerular filtration rate (GFR), detection of microalbuminuria (MAU) or depleted functional renal reserve (FRR), disorders of tubular function of the kidneys) and of studying cardiorenal relationships for the timely prescription of adequate therapy. The study performed allows optimizing the choice of therapy in elderly patients with AH.

The revealed nephroprotective effect of lisinopril and indapamide makes it possible to recommend their use in elderly patients with AH in order to reduce the risk of cardiovascular complications.

The results obtained have been introduced into the clinical practice of treatment of elderly patients with AH in the therapeutic and cardiological departments of Municipal Healthcare Institution City Clinical Hospital No. 3, the therapeutic department of the Federal State Institution Southern District Medical Center of the Russian Federation Public Health Service Clinical Hospital No. 3, Volgograd. The results of the study are used in the educational process at the Department of Internal Diseases of the Pediatric and Stomatological Faculties of Volgograd State Medical University for the training of students of the pediatric, stomatological and medico-biological faculties, as well as interns and clinical residents.

Main statements put forward for defense

1. In elderly patients with AH, in comparison with middle-aged AH patients, the prevalence of clinically significant GFR reduction, depleted FRR, the occurrence and the mean level of MAU reliably increase, and tubular dysfunction progresses. The most pronounced disorders of renal functions are recorded in elderly patients with isolated systolic AH (ISAH).

2. GFR reduction is most pronounced in elderly AH patients with insufficient decrease or increase in BP values at night, whereas depleted FRR is encountered more often in persons with excessive nocturnal BP decrease (predominantly diastolic). Concentric type of left ventricular hypertrophy (LVH) in elderly AH patients is associated with deterioration of renal functions — a reliable decrease in GFR and a greater severity of MAU. A close relationship between indicators of diastolic cardiac function and the functional state of the kidneys in elderly AH patients has been established.

3. Changes in HRV parameters — a decrease in the standard deviation of cardiointervals (SD), total power of the spectrum (TP) below 370 ms², an increase in the value of the centralization index (CI), the index of activity of regulatory systems (IARS), the stress index (SI), the coefficient of vagosympathetic interaction (LF/HF) above 1.5 — allow predicting the development of renal dysfunction in elderly patients with AH.

4. The increase in the aortic stiffness index in elderly patients with AH is interrelated with manifestations of renal dysfunction — an increase in MAU severity in patients with ISAH and a decrease in the daily urinary sodium excretion (DUSE) in persons with systolic-diastolic AH (SDAH).

5. A 12-week administration of lisinopril to elderly AH patients leads to a significant improvement in the morning BP dynamics, a decrease in interventricular septal thickness (IVST), promotes normalization of geometry (in 17.8% of cases; p<0.05) and diastolic function of the left ventricle (LV), reliably reduces the aortic stiffness index, which is closely interrelated with favorable dynamics of renal functions (normalization of GFR, FRR, tubular functions, decrease in MAU level — by 27%; p<0.05).

6. A 12-week indapamide therapy is accompanied by a more pronounced decrease in systolic BP (SBP) values in comparison with diastolic BP (DBP), exerts a favorable effect on SBP variability and the diurnal profile of DBP (normalization of the diurnal index in 11.5% of cases), leads to a reduction in the chamber dimensions of the left atrium (LA) (by 5%; p<0.05), significantly reduces the aortic stiffness index, which is accompanied by an improvement in the functional state of the kidneys (normalization of GFR, FRR, tubular functions, reduction in MAU severity by 25.1%; p<0.05).

7. Among elderly patients with AH, the most pronounced decrease in QoL indicators (44.98±2.52 points) and cognitive-mnestic functions (26.82±0.36 points) is initially recorded in patients with ISAH. Therapy with lisinopril and indapamide leads to positive dynamics of QoL indicators, while the administration of lisinopril is accompanied by a reliable improvement in cognitive-mnestic functions (by 4%; p<0.05).

The work was approved at a joint meeting of the departments of faculty therapy, cardiology with FD FUV, therapy and family medicine FUV, internal diseases of the pediatric and stomatological faculties, hospital therapy, propedeutics of internal diseases, infectious diseases with epidemiology, neurology, psychiatry, narcology and medical psychology with the course of psychiatry FUV, dermatovenereology, radiation diagnostics and radiation therapy of Volgograd State Medical University on January 30, 2008. The main provisions of the dissertation have been published in 17 works. The materials of the dissertation were presented and discussed at: the XIV Russian National Congress "Man and Medicine" (Moscow, 2007), the V Congress of Cardiologists of the Southern Federal District (Kislovodsk, 2006), the VI Congress of Cardiologists of the Southern Federal District (Rostov-on-Don, 2007), the Russian National Congress of Cardiologists and the Congress of Cardiologists of the CIS Countries (Moscow, 2007), the annual conferences of students and young scientists of VolgSMU (2006, 2007), the 11th Conference of Young Researchers of the Volgograd Region (2006), the 12th Regional Conference of Young Researchers of the Volgograd Region (2007), the VI European Congress of Gerontology (Saint Petersburg, 2007), the 10th Anniversary Scientific and Educational Forum Cardiology 2008 (Moscow, 2008), and the scientific-practical conference dedicated to the 60th anniversary of the State Healthcare Institution "Volgograd Regional Center for Medical Prevention" (2008).

Volume and structure of the work