Clinical and Diagnostic Features of the Twenty-Four-Hour Blood Pressure Profile in Patients with Arterial Hypertension of Various Origins

The dissertation is devoted to the study of the clinical and diagnostic features of the twenty-four-hour blood pressure (BP) profile in patients with arterial hypertension of various origins. It addresses the differential diagnosis between hypertensive disease and symptomatic (secondary) arterial hypertensions, including nephrogenic hypertension in chronic pyelonephritis and chronic glomerulonephritis, as well as hypertension in type 1 and type 2 diabetes mellitus and in persons occupationally exposed to small concentrations of lead. Particular emphasis is placed on analyzing the capabilities of twenty-four-hour blood pressure monitoring (ABPM), its individual and combined parameters, for assessing disease progression, predicting target organ damage, and differentiating nosological forms of arterial hypertension.

The work presents the results of a comparative study of standard and additional ABPM indices, their relationships with the stage of renal damage, left ventricular myocardial mass, and the double product level; an integral index for determining the type of the twenty-four-hour BP rhythm is proposed. The prognostic significance of ABPM indices depending on the origin of hypertension is evaluated, and the influence of small concentrations of lead on the twenty-four-hour BP profile is studied. The obtained results have been implemented into clinical practice and into postgraduate medical training programs.

Relevance of the problem. Russia is among the countries with the highest prevalence of arterial hypertension (AH), which constitutes a powerful negative factor affecting public health [234]. The prevalence of AH among Russian men is 41.1%, and among women 39.9% [176]. The economic damage caused by temporary or permanent loss of working capacity and by premature death due to arterial hypertension and its related complications — coronary heart disease (CHD) and cerebrovascular diseases (CVD) — in Russia alone amounted to about 29.3 billion rubles in 1999 [111].

At present, irrefutable evidence has been obtained that lowering elevated blood pressure (BP) reduces the risk of fatal and non-fatal cardiovascular complications [113, 144, 213, 235]. Numerous works have been devoted to the study of AH, and at present it is probably even difficult to estimate their number. According to Yu.V. Postnov, "despite the evident successes of the physiology of circulation in studying the mechanisms regulating BP and vascular tone, and the successes in the pharmacological control of BP and antihypertensive therapy, the nature of essential hypertension and its pathogenesis remain far from completely understood" [138, p. 5]. The problems of differential diagnosis between hypertensive disease (HD) and symptomatic arterial hypertension remain relevant. According to E.M. Evsikov (1999), at the new level of knowledge about the nature of AH, essential hypertension is shifting from the category of pathology with insufficient knowledge of its etiology and pathogenesis to that of diseases whose treatment effectiveness is limited by the lack of diagnostic capabilities of practicing physicians [56].

Renal hypertension is the largest group among secondary hypertensions [70, 106, 133]; chronic glomerulonephritis occupies the leading place among its causes [106]; chronic pyelonephritis and diabetic nephropathy are also significant because of their high prevalence [46, 106]. The question of the role of lead as one of the risk factors in the development of AH due to nephropathy continues to be debated [153]. According to N.A. Mukhin and co-authors (1997), "speaking of interstitial kidney diseases, which ultimately result in nephrosclerosis with AH and are acquiring increasing epidemiological significance, attention should be drawn to lead and cadmium nephropathies" [168, p. 6]. In renal hypertension, which is one of the leading signs of renal disease, "the diagnostic specificity of this sign is low" and "the connection between hypertension and renal disease cannot be established on the basis of any specific features of the hypertensive syndrome" [105]. Such an assessment of the diagnostic significance of the AH syndrome is apparently associated with the predominant use of clinical single-occasion BP measurements rather than its twenty-four-hour dynamics. Arterial hypertensions of various origins have certain specific features; for example, patients with diabetes mellitus (DM) have higher final BP values and constitute the group most resistant to AH treatment compared with patients without diabetes [284].

The auscultatory method of BP measurement, proposed in 1905 by N.S. Korotkov, is recognized as the official standard of non-invasive BP measurement for diagnostic purposes [163]. However, accumulated experience indicates that traditional single measurements do not always reflect the true BP, leaving open the question of the correctness of diagnosing elevated BP [47]. This method has drawbacks, the main ones being the difficulty of measurements during sleep, subjectivity, and the large scatter of the obtained values associated with diurnal BP fluctuations. The twenty-four-hour BP monitoring (ABPM) method allows the dynamics of BP to be assessed, is included in Russian and international recommendations for the management of patients with AH [14, 139, 377, 388, 389], and constitutes one of the most important achievements in cardiology in patient management [84]. According to experts of the European Society of Hypertension (2003): "For many years, twenty-four-hour BP monitoring was used for research purposes and is currently required in clinical pharmacological studies and in the evaluation of the effectiveness of new antihypertensive agents. At present, ABPM is becoming a mandatory procedure for the detection and treatment of arterial hypertension" [388]. The main directions of research on the twenty-four-hour BP monitoring method are the determination of normal ranges for ABPM indices; the establishment of relationships between traditionally measured BP and ABPM parameters; and the determination of the prognostic value of ABPM indices [116]. Twenty-four-hour BP monitoring indices are more closely related to target organ damage and the risk of death than clinical BP [80, 194, 200, 202, 230, 263, 264, 337]. However, the significance of ABPM parameters in the development of organ damage has not yet been determined [164]. The ABPM method is insufficiently used for the assessment of symptomatic hypertensions. According to I.M. Kutyrina and A.A. Mikhailov, 2000 [106], "there is almost no information on the features of the twenty-four-hour BP rhythm in renal hypertensions." In the literature there are single works discussing the possibility of using ABPM in the diagnosis of essential and secondary arterial hypertension in children [267]. When assessing BP dynamics under occupational exposures, office (clinical) pressure is usually used; the twenty-four-hour BP dynamics under exposure to heavy metals has not been studied. In diabetes mellitus, in most works ABPM is used predominantly to evaluate the effectiveness of antihypertensive therapy, or monitoring data are compared with clinical BP; investigations are more often devoted to type 2 diabetes [7, 207, 231, 299]. Studies of the twenty-four-hour BP dynamics in type 1 diabetes mellitus are conducted mainly in children and adolescents [196, 300]; single works investigate ABPM parameters in adult patients with type 1 DM [187, 196, 248].

Changes in standard and additional ABPM indices and their prognostic significance in DM depending on impaired renal functional capacity have been insufficiently studied.

Authors evaluating certain ABPM indices reveal similar changes in various pathologies: insufficient nocturnal BP reduction is recorded in patients with systolic hypertension [318, 321], hyperaldosteronism [233, 311], diabetes mellitus [3, 80], obstructive bronchitis [115], and chronic glomerulonephritis [162]. The possibility of using single parameters (twenty-four-hour rhythm, pressure load value) in the differential diagnosis of arterial hypertensions is even discussed [226, 267, 319]. The significance of isolated ABPM indices for organ damage and prognosis is probably overestimated, given the extremely large amount of information that can be obtained when this method is conducted.

Arterial hypertension and the kidneys have complex interrelationships; the differential diagnosis between HD and secondary hypertension in renal damage often presents considerable difficulties in clinical practice, and the development of effective AH treatment regimens is impossible without knowledge of the features of this syndrome depending on the nosology of the disease. A study comparing the features of the twenty-four-hour blood pressure profile in patients with arterial hypertension of various etiologies appears relevant.

Aim of the study — to establish the clinical and diagnostic significance of twenty-four-hour blood pressure profile indices depending on the origin of arterial hypertension (in patients with hypertensive disease, chronic pyelonephritis, chronic glomerulonephritis, diabetes mellitus, and in persons with the arterial hypertension syndrome who are exposed to small concentrations of lead).

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Tasks of the study

1. To conduct a comparative analysis of the clinical features of the chronic arterial hypertension syndrome in hypertensive disease, chronic pyelonephritis, chronic glomerulonephritis, and type 1 and type 2 diabetes mellitus.

2. To study the role of twenty-four-hour blood pressure monitoring indices in stage II–III hypertensive disease.

3. To determine differences in the dynamics of the twenty-four-hour blood pressure profile depending on the origin of nephrogenic hypertension in patients with chronic pyelonephritis and chronic glomerulonephritis.

4. To evaluate the most significant twenty-four-hour blood pressure profile indices in arterial hypertension in patients with type 1 and type 2 diabetes mellitus.

5. To investigate the effect of exposure to small concentrations of lead on the twenty-four-hour blood pressure profile.

Scientific novelty

New data have been obtained on the dependence of the prognostic value of twenty-four-hour blood pressure monitoring indices on the origin of arterial hypertension. It has been proved that in hypertensive disease, a disturbance of the twenty-four-hour blood pressure rhythm (the "night-peaker" rhythm type) characterizes the progression of the disease, in contrast to patients with nephrogenic hypertension (chronic glomerulonephritis and pyelonephritis). Arterial hypertension in chronic glomerulonephritis is characterized by a twenty-four-hour increase in diastolic (twenty-four-hour, maximum, and minimum values and time and area load indices over twenty-four hours, daytime, and nighttime) and mean dynamic (mean and minimum) blood pressure, whereas in chronic pyelonephritis only a decrease in rate indices is observed, in contrast to hypertensive disease.

Differences in the twenty-four-hour blood pressure dynamics in nephrogenic arterial hypertension have been established: in chronic pyelonephritis, the progression of renal disease is interrelated with the main twenty-four-hour blood pressure monitoring parameters (twenty-four-hour systolic, diastolic, and pulse blood pressure; systolic and diastolic pressure load indices), whereas such a relationship is absent in chronic glomerulonephritis.

Significant indices have been determined for the prognosis of progression of diabetic nephropathy regardless of the type of diabetes mellitus (twenty-four-hour minimum values of systolic, pulse, and mean dynamic blood pressure; mean double product; systolic pressure time index over twenty-four hours and during daytime). The leading difference between arterial hypertension in type 1 and type 2 diabetes mellitus and hypertensive disease consists of a pronounced disturbance of the twenty-four-hour blood pressure rhythm and an increase in the double product over twenty-four hours.

It has been proved that lead in small concentrations is not a risk factor for arterial hypertension; among persons occupationally exposed to lead, arterial hypertension and arterial hypotension are recorded equally. A relationship has been established between blood lead content and inversion of the twenty-four-hour blood pressure rhythm (according to the SI 3 index).

Practical significance of the work

For hypertensive disease, the following most significant blood pressure indices have been proposed for assessing disease progression: twenty-four-hour rhythm type, twenty-four-hour systolic and pulse pressure, systolic pressure time and area indices over twenty-four hours, and pulse pressure area index. The study has demonstrated the significance of the mean, maximum, and minimum values and of the time and area indices of diastolic pressure for the differential diagnosis of hypertensive disease and arterial hypertension in chronic glomerulonephritis. The main indices (minimum values of systolic, pulse, and mean dynamic blood pressure; mean double product over twenty-four hours, daytime and nighttime) have been determined for assessing the prognosis of progression of renal failure in patients with arterial hypertension and diabetes mellitus. The data obtained make it possible to propose that occupational exposure to lead be included among the indications for twenty-four-hour blood pressure monitoring. An integral index (SI 3) has been proposed for determining the type of twenty-four-hour blood pressure rhythm.

Main statements to be defended

1. In the assessment of the chronic arterial hypertension syndrome, significance is attached to a specific combination of twenty-four-hour blood pressure monitoring indices; the significance of these indices differs in patients with hypertensive disease, renal diseases, and diabetes mellitus.

2. A disturbance of the twenty-four-hour blood pressure rhythm (nocturnal hypertension) characterizes the progression of the disease in hypertensive disease, in contrast to patients with renal diseases and diabetes mellitus. Systolic, diastolic, pulse, and mean dynamic blood pressure are interrelated with the stage of renal damage in chronic pyelonephritis, whereas such a relationship is not recorded in chronic glomerulonephritis. The double product (over twenty-four hours, daytime and nighttime) is a significant twenty-four-hour monitoring index for determining the prognosis in arterial hypertension in patients with type 1 and type 2 diabetes mellitus.

3. Twenty-four-hour blood pressure monitoring makes it possible to determine the nature of possible relationships between small concentrations of lead and blood pressure level.

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Implementation into practice

The results of the study have been implemented in the work of the departments of the Republican Clinical Hospital named after G.G. Kuvatov (Ufa). New criteria for assessing the twenty-four-hour blood pressure dynamics are being used: determination of the twenty-four-hour BP rhythm by the SI 3 index and the mean double product over twenty-four hours for assessing the progression of renal damage in patients with diabetes mellitus. The theoretical propositions (changes in the twenty-four-hour BP profile depending on the etiology of arterial hypertension) and practical recommendations (assessment of the progression of hypertensive disease using the twenty-four-hour BP index, assessment of treatment effectiveness in patients with diabetes mellitus and arterial hypertension) based on the materials of the work have been incorporated into the training program for internists, residents, and postgraduate trainees at the Department of Therapy of the Institute of Postgraduate Education of the Bashkir State Medical University. In the course of the study, methodological recommendations have been developed for internists and trainees of the Institute of Postgraduate Education of BSMU. Within the framework of the program "State Priorities of Public Health of the Republic of Bashkortostan: Disease Prevention and Medical Technologies," a research project "Arterial Hypertension under Exposure to Heavy Metals" was carried out in 1999–2002; its results have been implemented in the work of the Ufa Research Institute of Occupational Medicine and Human Ecology. In addition to the generally accepted methods of examination of persons occupationally exposed to lead, twenty-four-hour BP monitoring has been included. The developed supplements to the scheme for filling in the Registration and Follow-up Cards of Patients with Diabetes Mellitus of the State Register have been implemented in the Republic of Bashkortostan on the basis of the informational and methodological recommendations 'State Register of Patients with Diabetes Mellitus in the Republic of Bashkortostan. Diabetes Mellitus and Arterial Hypertension. Guidelines for the Maintenance of Territorial Databases of the State Register of Patients with Diabetes Mellitus', Ufa, 2005.

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Approbation of the work

The main propositions of the dissertation have been reported at the Russian Conference "Treatment and Prevention of Arterial Hypertension" (Moscow, 2000), the 1st All-Russian Conference "Preventive Cardiology" (Moscow, 2000), the Conference of the Tyumen Cardiology Center with International Participation (Tyumen, 2000), the International Symposium "Current Problems of Reproductive Health under Anthropogenic Pollution" (Kazan, 2001), the All-Russian Conference "Modern Possibilities of Effective Prevention, Diagnosis, and Treatment of Arterial Hypertension" (Moscow, 2001), the Republican Conferences of Endocrinologists "Current Problems of Diagnosis, Treatment, and Prevention of Endocrine System Diseases" (Ufa, 2003, 2004), the Russian National Congresses of Cardiologists (Moscow, 2001, 2005), the meeting of the Problem Commission "Cardiology" of the Bashkir State Medical University (Ufa, 2006), and the joint meeting of the staff of the Department of Hospital Therapy No. 1 of the Medical Faculty of the Russian State Medical University and the staff of City Clinical Hospital No. 15 (Moscow, 2006).