Coronary heart disease and angina pectoris in patients with rheumatoid arthritis

The prevalence of coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) is not precisely known. The vast majority of studies have examined mortality from cardiovascular diseases, including CHD, in patients with RA. The risk of myocardial infarction is 2 times higher in women with RA than in women without it. Asymptomatic myocardial infarction and sudden death are highly common in patients with RA; at the same time, angina pectoris is significantly less common than in individuals without RA.

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Symptoms of angina in rheumatoid arthritis

Symptoms of exertional angina (the main clinical form of ischemic heart disease) are less common in patients with RA than in patients without RA. The attenuation of angina symptoms may be due to the use of NSAIDs. The use of special questionnaires (for example, the Rose questionnaire) for diagnosing angina is not entirely correct in the case of RA. The fundamental characteristic of angina - the relationship with physical activity - cannot be determined adequately due to a decrease in physical activity and the frequent inability to perform the load necessary to establish angina (for example, climbing stairs). It is important to remember that rheumatoid arthritis is more often observed in young and middle-aged women; most doctors tend to regard the appearance of pain or discomfort in the chest in a woman as a symptom of a disease of the musculoskeletal system or the onset of menopause.

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

Risk factors for coronary heart disease in patients with rheumatoid arthritis

Risk factor	Comment
Age	Men >55 years, women >65 years
Floor	Female gender is a factor of unfavorable prognosis of RA in young 1 middle age
Body Mass Index (BMI)	Obesity (BMI <30 kg/m2 ) Underweight (BMI <20 kg/ m2 )
Lipid profile	Decreasing total cholesterol and high-density lipoprotein cholesterol, increasing blood triglyceride levels
High-density lipoprotein level	It is inversely related to the levels of inflammation markers (CRP and ESR)
Arterial hypertension	Observed in 70% of RA patients
Rheumatoid factor	Rheumatoid factor seropositivity
RA activity	High clinical and laboratory activity of RA
Number of swollen joints	2 or 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 in 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/m2 ^], as well as underweight (BMI <20 kg/m2 ⁾ are risk factors in patients with RA. The lipid profile in RA is characterized by a decrease in total cholesterol and high-density lipoprotein (HDL) cholesterol, as well as an increase in the blood triglyceride content. In addition, an increase in the number of small dense particles of low-density lipoprotein cholesterol is observed. In RA, the level of HDL cholesterol is inversely related to the levels of inflammatory markers (CRP and ESR); while disease-modifying therapy for RA leads, along with a decrease in ESR and CRP, to an increase in HDL cholesterol.

Arterial hypertension (AH) is observed in 70% of patients with RA, is underdiagnosed and insufficiently treated. It is necessary to take into account that the use of NSAIDs and glucocorticoids aggravates AH and reduces the effectiveness of antihypertensive treatment.

Several studies have identified factors of unfavorable prognosis for cardiovascular disease that are characteristic of RA. Seropositivity for rheumatoid factor, especially in early RA (less than a year old), 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 with patients without swollen joints. High ESR (>60 mm/h, recorded at least 3 times) and baseline CRP >5 mg/L are independent predictors of cardiovascular death in RA patients, with the relative risk being 7.4 (95% confidence interval 1.7-32.2) in seropositive patients with high CRP. Extra-articular manifestations (rheumatoid vasculitis and lung involvement) are predictors of cardiovascular mortality.

Classification

The classification of coronary heart disease in patients with rheumatoid arthritis does not differ from that used in clinical practice. The functional class of angina is determined according to the Canadian classification. If dyslipidemia and arterial hypertension are present, they must be indicated in the diagnosis.

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Diagnosis of coronary heart disease and angina in rheumatoid arthritis

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

The following factors are used to determine the risk: gender, age, smoking, systolic blood pressure and total cholesterol. The risk of a fatal event (5% or more) within the next 10 years is considered high.

Unfortunately, for many patients with RA, the SCORE risk assessment may underestimate the risk, especially when using the total cholesterol version. For example, a 59-year-old non-smoking woman with RA has a physician-measured BP of 140/85 mmHg and a total cholesterol level of 5.1 mmol/L (HDL cholesterol 0.85 mmol/L). When assessed using SCORF, the risk is 2%. However, the patient has 16 swollen joints, is seropositive for rheumatoid factor, has an ESR of 75 mm/h, and has a CRF of 54 mg/L. Does this patient really have a low risk of a fatal cardiovascular event? The real risk may exceed 5%. Clearly, for patients with RA, in addition to SCORE, an expanded examination using instrumental methods and subsequent clarification of the risk category is necessary. An increase in the intima-media complex, considered as subclinical atherosclerosis, was demonstrated in patients with RA compared with controls. This approach is limited by the lack of a unified methodology; in addition, the correlation between the severity of carotid and coronary atherosclerosis is very moderate.

EchoCG with assessment of systolic and diastolic functions of the left ventricle, as well as calculation of the left ventricular myocardial mass index is a common and valuable diagnostic method. Left ventricular hypertrophy, its systolic dysfunction and remodeling allow assessing the risk of chronic heart failure (CHF).

Electron beam or multispiral computed tomography can assess the extent of coronary artery calcification, which reflects the severity of atherosclerosis. In patients with RA, coronary artery calcification is most pronounced in the long-term course of the disease. Unfortunately, when assessing the extent 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 for acute coronary events in patients with RA will be low, although this issue requires study in prospective studies. In addition, both methods are not always available in real-life practice.

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

Studies using coronary angiography have shown that RA patients have three coronary vessels affected more often than controls. Coronary angiography, the “gold standard” of diagnostics, can detect atherosclerotic stenosis of the coronary arteries, but is not applicable for assessing the state of the microcirculatory bed and inflammation of the arterial wall.

A possible effective method for diagnosing microcirculation disorders is myocardial scintigraphy. Single studies have demonstrated a high frequency of myocardial perfusion defects (up to 50%) in patients with RA. The method is limited due to its complexity and high cost.

With the help of daily blood pressure monitoring, it is possible to identify patients with insufficient blood pressure reduction at night, while the blood pressure values recorded during the daytime do not exceed the normal limit; hypertension at night is an independent factor of unfavorable prognosis.

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

A new factor of unfavorable cardiovascular prognosis is obstructive sleep apnea syndrome (OSAS). Questionnaires (for example, the Epfort scale) can be used for screening. The "gold standard" of diagnostics is polysomnography, the implementation of which is associated with a large number of material and technical difficulties. An accessible alternative is cardiorespiratory monitoring of the patient's sleep, during which three parameters are recorded - air flow, O2 saturation ₎, and heart rate. The results of cardiorespiratory monitoring correlate well with polysomnography data; this method can be used at the outpatient stage to diagnose OSAS.

According to limited data, OSA is often observed in patients with RA - in almost 50% of cases.

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Clinical observation

Patient Z., 56 years old, was admitted to the rheumatology department of City Clinical Hospital No. 1 named after N.I. Pirogov in March 2008 with complaints of morning stiffness for 1.5 hours, pain, limited movement in the metacarpophalangeal, wrist, knee, ankle joints, dry mouth, pain and sore throat.

It is known from the anamnesis that the patient has been ill since September 1993, when she began to complain of pain in the metacarpophalangeal and wrist joints, and morning stiffness. She was consulted by a rheumatologist, examined, and diagnosed with rheumatoid arthritis, seropositive. Treatment was with sulfasalazine, without effect. In 1995-1996, treatment was with taursdone (at that time, the drug was registered in the Russian Federation) with a positive effect, but the drug was discontinued due to the development of nephropathy. Hydroxychloroquine (plaquenil) was prescribed as a basic treatment. Progression of the disease was noted against the background of treatment with hydroxychloroquine, the drug was discontinued, and in 1999, treatment with methotrexate was started at a dose of 7.5 mg / week. Due to an increase in liver enzymes (AST, ALT), the drug was discontinued after 6 months.

Until 2003, the patient did not receive disease-modifying therapy. In 2003, due to high disease activity, prednisolone was started. Since 2005, leflupomide at a dose of 20 mg was prescribed as a basic therapy, which she took until autumn 2007. In October 2007, the patient developed acute laryngotracheitis; relapsing polychondritis diathesis was suspected, in connection with which inpatient treatment was carried out and methylprednisolone was started at a dose of 24 mg/day. The diagnosis was not confirmed, but a feeling of irritation in the throat and sore throat persisted. The dose of methylprednisolone was gradually reduced, and since February 2008 the patient has been receiving 9 mg/day. From 2004 to the present, the patient has been taking HIIBC (diclofenac) orally in courses.

Since February 2008, joint pain and morning stiffness began to increase, which is why the patient was hospitalized.

On admission, the patient's condition is satisfactory. On examination: hypersthenic build. Height 160 cm, weight 76 kg. Waist circumference 98 cm, hip circumference 106 cm, neck circumference 39 cm. The skin is of normal color, puffiness of the face is noted. Lymph nodes are not palpable. In the lungs, vesicular breathing is heard, wheezing is not auscultated. Respiratory rate is 17 per minute. Heart sounds are muffled, the rhythm is regular. HR 100 per minute. BP 130/80 mm Hg. The abdomen is soft and painless on palpation. The liver is palpable at the edge of the costal arch, painless; the spleen is not palpable. There is no peripheral edema.

Status heath. Pain was detected on palpation and movement in the metacarpophalangeal joints (1st, 3rd, 4th on the right and 2nd, 3rd on the left), 3rd proximal interphalangeal joint of the right hand, ankle joints and metatarsophalangeal joints of both feet. Defiguration due to exudative-proliferative changes in the 1st, 3rd metacarpophalangeal joints on the right, 3rd, 4th proximal interphalangeal joints on the right, both ankle joints. Defiguration of the wrist joints due to proliferative changes. Hypotrophy of the intercostal muscles, the strength of clenching the hand into a fist is reduced on both sides. Flexion contracture of the left elbow joint. Pain on the visual analogue scale (VAS) is 55 mm. Number of swollen joints (count 44 joints) - 6. Ritchie index - 7.

Blood tests on admission: Hb - 141 t/l, leukocyte formula unchanged, 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 (AST - 50 U/l, ALT - 48 U/l), total cholesterol up to 7.1 mmol/l. Blood glucose - 4.5 mmol/l. CRV - negative. Latex test 1:40.

X-rays of the hands revealed marked osteoporosis of the heads of the metacarpal, phalangeal and carpal bones. Cystoid enlightenment and multiple erosions of the articular surfaces of the carpal bones, more on the left. Subchondral sclerosis. Noticeable narrowing of the spaces of the wrist joints, less so of the interphalangeal and metacarpophalangeal articulations. Subluxation in the metacarpophalangeal articulation of the first finger on the right.

Radiographs of the knee joints in two projections revealed pronounced focal osteoporosis. Subchondral sclerosis. Noticeable uneven narrowing of the interarticular spaces, more on the right.

The ECG shows pronounced sinus tachycardia. Heart rate is 130 beats per minute. Normal position of the electrical axis of the heart, without pathological changes.

Disease activity according to 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 (X-ray stage III), FC II,

The patient underwent additional examination methods (echoCG, Holter ECG monitoring with heart rate variability analysis, 24-hour blood pressure monitoring, duplex ultrasound scanning of the carotid arteries, cardiorespiratory monitoring). The 10-year risk of developing cardiovascular events was assessed using the SCORE scale.

Results of the examination: the risk of fatal cardiovascular disease according to the SCORE scale was 1.4%. EchoCG revealed signs of left ventricular myocardial hypertrophy (left ventricular myocardial mass index - 100 g/m2 ⁾, diffuse decrease in contractility - ejection fraction (EF) 45%. Duplex scanning of the carotid arteries: an atherosclerotic plaque was detected on the right in the bifurcation area of the common carotid artery, stenotic the lumen by 20% (Fig. 1-3).

Holter ECG monitoring with heart rate variability analysis: sinus rhythm with an average heart rate of 100 per minute was recorded over a day. A decrease in SDNN was noted, rMSSD. pNN50 indicators were within the normal range (SDNN - 67 ms, rMSSD = 64 ms, pNN50 = 12.1%).

Daily blood pressure monitoring: average blood pressure readings during the day were 146/86 mm Hg. Blood pressure increases were recorded at night: average night-time blood pressure readings were 162/81 mm Hg.

Cardiorespiratory monitoring revealed severe OSA (apnea-hypopnea index 49, normal less than 5).

In a non-smoking patient with no complaints of pain or discomfort in the chest, no history of hypertension and normal blood pressure values measured by a physician, the overall risk

Cardiovascular disease was low. However, extensive clinical and instrumental examination revealed both subclinical atherosclerosis of the carotid artery and the following factors of unfavorable prognosis:

• left ventricular hypertrophy;
• nocturnal hypertension;
• decreased heart rate variability;
• OSA.

Thus, in the case under consideration, a comprehensive analysis revealed a high risk of cardiovascular complications, 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.

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Treatment of angina in rheumatoid arthritis

Treatment of angina in a patient with RA should include not only antianginal agents, 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 without clinical manifestations of coronary heart disease, correction of traditional risk factors and control of disease activity using disease-modifying agents 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 lung cancer. ACE inhibitors, according to several small studies, improve endothelial function in patients with RA. 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 features of the circadian rhythm of blood pressure in a particular patient.

Treatment of OSA with continuous positive airway pressure devices during sleep is effective in patients in the general population and may be recommended for 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 extra-articular manifestations.

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