Coronary artery disease and angina pectoris in patients with rheumatoid arthritis

The prevalence of ischemic heart disease (CHD) in patients with rheumatoid arthritis (RA) is not known. In the vast majority of studies, mortality from cardiovascular diseases, including CHD, among RA patients was studied. The risk of myocardial infarction is 2 times higher in women with RA than in women who do not. In patients with RA, asymptomatic myocardial infarction and sudden death occur with high frequency; at the same time, angina pectoris is much less common than in non-RA patients.

[1], [2], [3], [4], [5], [6], [7], [8], [9]

Symptoms of angina in rheumatoid arthritis

Symptoms of angina pectoris (main: clinical form of ischemic heart disease) are less common in patients with RA than in patients without RA. The erosion of symptoms of angina may be due to the intake of NSAIDs. The use of special questionnaires (for example, the Rose questionnaire) for the diagnosis of angina pectoris is not entirely correct in the case of RA. The underlying characteristic of angina pectoris is the connection with physical exertion - ne can be determined adequately due to a decrease in physical activity and frequent inability to perform the load necessary to establish angina pectoris (for example, climbing the stairs). It is important to remember that rheumatoid arthritis is more often observed in women of young and middle age; most physicians are inclined to regard the appearance of pain or discomfort in the chest of a woman as a symptom of locomotor system disease or coming menopause.

Of great importance is the identification of cardiovascular risk factors, both traditional and specific for RA.

Risk factors for coronary heart disease in patients with rheumatoid arthritis

Risk Factor	A comment
Age	Men> 55 years, women> 65 years
Floor	Female gender is a factor of the unfavorable prognosis of RA in young middle age
Body mass index (BMI)	Obesity BMI <30 kg / m 2 ) Deficiency of body weight (BMI <20kg / m 2 )
Lipid profile	Decreased levels of total cholesterol and high-density lipoprotein cholesterol increase in blood levels of triglycerides
The level of high density lipoproteins	It is inversely related to levels of inflammatory markers (SRV and ESR)
Arterial hypertension	It is observed in 70% of RA patients
Rheumatoid factor	Seropositivity for rheumatoid factor
RA activity	High clinical and laboratory activity of RA
The number of swollen joints	2 and more

Cardiovascular morbidity and mortality increase with age in both RA patients and the general population. Female gender is a factor of unfavorable prognosis in RA at young and middle age. It is necessary to take into account the duration of smoking and the number of cigarettes smoked.

Obesity [body mass index (BMI)> 30 kg / m ² ], as well as a body mass deficit (BMI <20 kg / m ² ) are risk factors in RA patients. The lipid profile in RA is characterized by a decrease in the level of total cholesterol and high-density lipoprotein cholesterol (HDL), as well as an increase in blood triglycerides. In addition, there is an increase in the number of fine dense cholesterol particles of low-density lipoproteins. In RA, the level of HDL cholesterol is inversely related to levels of inflammatory markers (CRP and ESR); while the disease-modifying treatment of RA leads, along with a decrease in ESR and CRP, to an increase in HDL cholesterol.

Arterial hypertension (AH) is observed in 70% of RA patients, it is insufficiently diagnosed and not effectively treated. It should be noted that the administration of NSAIDs and glucocorticoids exacerbates hypertension and reduces the effectiveness of antihypertensive treatment.

In several studies, the factors of unfavorable prognosis for cardiovascular diseases, characteristic for RA, were revealed. Seropositive for rheumatoid factor, especially in early RA (lasting less than a year), increases the risk of cardiovascular events by 1.5-2 times. High clinical and laboratory activity of the disease also serves as a predictor of unfavorable prognosis. The risk of cardiovascular mortality in RA patients with two or more swollen joints is 2.07 (95% confidence interval - 1.30-3.31) compared to patients who have no swollen joints. A high level of ESR (> 60 mm / h, recorded at least 3 times) and baseline CRP> 5 mg / L are independent predictors of cardiovascular death in RA patients, and in seropositive patients with high CRP, the relative risk is 7 , 4 (95% confidence interval - 1.7-32.2). Extra-articular manifestations (rheumatoid vasculitis and lung damage) serve as predictors of cardiovascular mortality.

Classification

Classification of IHD in patients with rheumatoid arthritis does not differ from that used in clinical practice. The functional class of angina is determined by the Canadian classification. In the presence of dyslipidemia and arterial hypertension, they must be indicated in the diagnosis.

[10], [11], [12], [13]

Diagnosis of IHD and angina in rheumatoid arthritis

According to current European and Russian recommendations, the SCORE model should be used to assess the risk of a fatal cardiovascular event, including in RA patients.

To determine the risk, the following factors are used: sex, age, smoking, systolic blood pressure and total cholesterol. High consider the risk of a fatal event (5% or more) over the next 10 years.

Unfortunately, for many RA patients, SCORE risk assessment may underestimate the risk, especially when using a version with a common cholesterol. For example, a nonsmoking 59-year-old woman suffering from RA, BP when measured by a doctor 140/85 mm Hg, the total cholesterol level is 5.1 mmol / L (HDL cholesterol 0.85 mmol / L). When assessed by SCORF, the risk is 2%. However, in the patient 16 swollen joints, seropositivity for rheumatoid factor, ESR - 75 mm / h, SRV - 54 mg / l. Is this patient a low risk of a fatal cardiovascular event? The actual risk may exceed 5%. Obviously, for RA patients in addition to SCORE, an extensive examination using instrumental methods and a subsequent refinement of the risk category is necessary. An increase in the intima-media complex, regarded as subclinical atherosclerosis, in patients with RA compared with control subjects was demonstrated. This approach limits the lack of a unified methodology; In addition, the correlation between the severity of carotid and coronary atherosclerosis is very moderate.

Echocardiography with an evaluation of the systolic and diastolic functions of the left ventricle, as well as the calculation of the left ventricular myocardial mass index is a common and valuable method of diagnosis. Hypertrophy of the left ventricle, its systolic dysfunction and remodeling allow assessing the risk of chronic heart failure (CHF).

Electron beam or multispiral computed tomography makes it possible to assess the severity of coronary artery calcification, which reflects the severity of atherosclerosis. In patients with RA, calcification of the coronary arteries is most pronounced in the course of a long course of the disease. Unfortunately, in assessing the severity of calcification, it is impossible to take into account the role of coronary artery inflammation and plaque stability; it can be assumed that the predictive value of electron beam or multispiral computed tomography with respect to acute coronary events in RA patients will be low, although this issue needs to be studied in prospective studies. In addition, both methods are not always available in real practice.

Load tests (bicycle or treadmill-ergometry) have limited application in patients with RA because of the objective impossibility of achieving submaximal heart rate and limited functionality of patients. The latter circumstance complicates the interpretation of the Holter monitoring of the ECG, used to diagnose asymptomatic myocardial ischemia.

Studies using coronary angiography demonstrated that in RA patients, more than three coronary vessels are affected more often than in control subjects. Coronary angiography, the "gold standard" of diagnosis, allows us to detect atherosclerotic stenoses of the coronary arteries, but is not applicable for assessing the microcirculatory bed and inflammation of the arterial wall.

Possible effective method for the diagnosis of microcirculation disorders is myocardial scintigraphy. In single studies, a high incidence of myocardial perfusion defects (up to 50%) in RA patients was demonstrated. The method is limited because of complexity and high cost.

With the daily monitoring of blood pressure, patients with insufficient BP decrease at night can be identified, while the values of blood pressure recorded in the daytime do not exceed the norm, AG in the night period is an independent factor of the unfavorable prognosis.

A possible method for assessing the risk of cardiovascular events in RA patients is the simultaneous study of inflammatory markers and activity of the sympathetic nervous system. High CRP and low heart rate variability (reflecting the predominance of sympathetic activity) together have a high predictive value for myocardial infarction and death; individually the predictive value of the factors is reduced. According to a study conducted at the Department of Faculty Therapy them. Acad. A.I. Nesterov RSMU. Low heart rate variability (with Holter ECG monitoring) is clearly associated with high inflammatory activity of the disease in RA patients. The variability of the heart rate decreases with the progression of coronary atherosclerosis and can serve as a predictor of life-threatening arrhythmias. At the same time, a high incidence of sudden death is observed in RA. Thus, simultaneous assessment of inflammatory activity of RA and heart rate variability may be an additional method of identifying patients at high risk of cardiovascular events.

The new factor of an unfavorable cardiovascular prognosis is the obstructive sleep apnea syndrome (OSAS). For screening, you can use questionnaires (for example, the scale of EpFort). The "gold standard" of diagnostics is polysomnography, the implementation of which involves a lot of material and technical difficulties. Available alternative - cardiorespiratory monitoring of patient sleep, during which recorded three parameters - airflow saturation O ₂ ), and heart rate. The results of cardiorespiratory monitoring correlate well with polysomnography data, this method can be used in the outpatient stage for diagnosis of OSAS.

According to a few data, OSAS is often observed in RA patients - almost in 50% of cases.

[14], [15], [16], [17], [18]

Clinical observation

Patient Z., 56 years old, entered the department of rheumatology of the State Clinical Hospital № 1 named after. N. Pirogova in March 2008 with complaints and morning stiffness for 1.5 hours, pain, restriction of movement in metacarpophalangeal, wrist, knee, ankle joints, dry mouth, pain and sore throat.

From the anamnesis it is known that the patient is sick since September 1993, when she began to worry about pain in the metacarpophalangeal, wrist joints, morning stiffness. Advised rheumatologist, conducted a survey, diagnosed with "rheumatoid arthritis, seropositive." Sulfasalazine was treated with no effect. In 1995-1996 years. Were treated with taursdon (at that time the drug was registered in the Russian Federation) with a positive effect, but the drug was canceled due to the development of nephropathy. As a basic effect, hydroxychloroquine (plakvenil) was prescribed. On the background of treatment with hydroxychloroquine, the progression of the disease was noted, the drug was withdrawn, and since 1999 treatment with methotrexate was started at a dose of 7.5 mg / week. In connection with the increase in hepatic enzymes (ACT, ALT) after 6 months the drug was canceled.

Until 2003, the patient did not receive a disease-modifying treatment. In 2003, and the association of high disease activity, began to use prednisolone. Since 2005, leflupomide was prescribed as a basic therapy in a dose of 20 mg, which was taken until the fall of 2007. In October 2007, the patient developed acute laryngotracheitis assumed a diathesis of recurrent polychondritis, which led to inpatient treatment and began to give methylprednisolone in a dose 24 mg / day. The diagnosis is not confirmed, but there was a feeling of perspiration in the throat, sore throat. The dose of methylprednisolone was gradually reduced, and from February 2008 the patient received 9 mg / day. In the period from 2004 to the present, the patient took HIIBC (diclofenac) inward courses.

Since February 2008, the pain began to increase in the joints, morning stiffness, in connection with which the patient was hospitalized in a hospital.

At admission, the patient's condition is satisfactory. On examination: hypersthenic physique. Height 160 cm, weight 76 kg. The waist circumference is 98 cm, the hip circumference is 106 cm, the neck circumference is 39 cm. The skin is of ordinary color, the puffiness of the face is noted. Lymph nodes are not palpable. In the lungs, the breath is vesicular, the wheezing is heard. The respiration rate is 17 per minute. The heart sounds are muffled, the rhythm is correct. HR of 100 per minute. Blood pressure 130/80 mm Hg The abdomen is soft, painless when palpated. The liver is palpable at the edge of the costal arch, painless; the spleen is not palpable. Peripheral edema is absent.

Status heath. Painfulness in palpation and movements was detected. In the metacarpophalangeal joints (1,3, 4-on the right and 2-nd, 3 on the left), the 3rd proximal interphalangeal joint of the right hand, ankles and metatarsophalangeal joints of both feet. Defogation due to exudative-proliferative changes in the 1st, 3rd metacarpophalangeal joints on the right, 3rd, 4th proximal interphalangeal on the right, both ankle joints. Deficiency of wrist joints due to proliferative changes. Hypotrophy of intercostal muscles, the force of compression of the hand into the fist is reduced on both sides. Flexural contracture of the left elbow joint. Pain on the visual analog scale (VASH) - 55 mm. The number of swollen joints (account of 44 joints) is 6. Richie's index is 7.

In blood tests for admission Nb - 141 t / l, the leukocyte formula is not changed, ESR - 55 mm / h, total protein - 67.0 g / l, urea - 5.1 mmol / l, bilirubin - 1.7.2-0 -17.2 μmol / l, increased enzymes (ACT - 50 U / l, ALT - 48 U / l), total cholesterol to 7.1 mmol / l. Blood glucose is 4.5 mmol / l. SRV - negative. Latex test 1:40.

On the radiographs of the brushes, pronounced osteoporosis of the metacarpal, phalanx and bones of the wrist. Brush enlightenment and multiple erosions of the articular surfaces of the bones of the wrist, more to the left. Subchondral sclerosis. Noticeable narrowing of the slits of the wrist joints, less - interphalangeal and metacarpophalangeal joints. Subluxation in metacarpophalangeal articulation 1 finger to the right.

On the radiographs of the knee joints in two projections, pronounced focal osteoporosis was detected. Subchondral sclerosis. Noticeable uneven narrowing of interarticular cracks, more to the right.

On the ECG, pronounced sinus tachycardia is noticeable. Heart rate is 130 per minute. Normal position of the electric axis of the heart, without pathological changes.

The disease activity for DAS28 and DAS4 was 4.24 and 2.92, respectively, which corresponds to moderate activity.

Clinical diagnosis: rheumatoid arthritis seropositive, late stage, activity II (DAS28 4,24), erosive (radiological stage III), II FC,

The patient underwent additional research methods (Echocardiography, Holter ECG monitoring with heart rate variability analysis, 24-hour blood pressure monitoring, duplex ultrasound carotid artery scanning, cardiorespiratory monitoring). A 10-year risk of developing cardiovascular events according to the SCORE score is estimated.

Results of the survey: the risk of fatal cardiovascular disease according to the SCORE scale was 1.4%. With the help of echocardiography, signs of myocardial hypertrophy of the left ventricle (myocardial mass index of the left ventricle - 100 g / m ² ), diffuse decrease in contractility - ejection fraction (FV) of 45%. Duplex scanning of carotid arteries: an atherosclerotic plaque is found on the right in the bifurcation region of the common carotid artery, stenosing the lumen by 20% (Figure 1-3).

Holter ECG monitoring with heart rate variability analysis: a sinus rhythm with an average heart rate of 100 per minute was recorded per day. There was a decrease in SDNN, rMSSD. PNN50 within the norm (SDNN - 67 ms, rMSSD = 64 ms, pNN50 = 12.1%).

Daily monitoring of blood pressure: mean BP values for the daytime period were 146/86 mm Hg. The increase in blood pressure during the night period was recorded: the mean BP values were 162/81 mm Hg.

Cardiorespiratory monitoring revealed an acute OSA of a serious degree of severity (apnea-hypopnea index 49, norm less than 5).

In a non-smoking patient with no complaints of pain or discomfort and chest, with no history of AH and normal BP values when measured by a physician, the total risk

Cardiovascular disease was low. However, with an expanded clinical and instrumental examination, both subclinical carotid artery atherosclerosis and the following unfavorable prognosis factors were identified:

• left ventricular hypertrophy;
• night AG;
• decreased heart rate variability;
• OSAS.

Thus, in the case examined, due to a complex analysis, a high risk of cardiovascular complications is established, in connection with which the patient is shown non-drug measures and drug treatment aimed at reducing the risk.

The given clinical example illustrates the need to use modern methods of assessing cardiovascular risk in this category of patients.

[19], [20], [21], [22], [23], [24], [25]

Treatment of angina in rheumatoid arthritis

Treatment of angina in a patient with RA should include not only angianginal drugs, but also drugs that improve the prognosis [statins, acetylsalicylic acid, ACE inhibitors (ramipril, perindopril), beta-blockers in the case of a previous myocardial infarction].

In patients who do not have clinical manifestations of IHD, correction of traditional risk factors and control of disease activity by disease-modifying effect are necessary. Statins should be prescribed to patients with dyslipidemia and / or documented subclinical atherosclerosis; there is evidence of their anti-inflammatory effects in patients with RL. ACE inhibitors, according to several small studies, improve endothelial function in RA patients. In any case, in the presence of hypertension, antihypertensive treatment is necessary. It is necessary to take into account possible drug interactions (with NSAIDs) and the peculiarities of the daily rhythm of BP in a particular patient.

The treatment of OSAS with devices that create a constant positive airway pressure during sleep is effective in patients in the general population and can be recommended to patients with RA.

Forecast

IHD is the cause of death in 35-50% of cases in patients with rheumatoid arthritis. The prognosis is worse with high RA activity and with extra-articular manifestations.

[26], [27]