Managing Hypertensive Patients With Gout Who Take Thiazide - Handler - 2. The Journal of Clinical Hypertension. Case 1: A 6. 7- year- old man was referred to our hypertension clinic because of refractory hypertension associated with gout. The onset of hypertension occurred in his 2. Blood Pressure; Gout Drug Protective, Study Finds. Blood Pressure; Gout Drug Protective, Study. Since his early 3. Approximately 1 year prior to his hypertension evaluation, the patient was prescribed allopurinol and last experienced podagra 6 months previously. 31 Decreasing uric acid levels using allopurinol in patients with. Elevated serum uric acid concentration is a common laboratory finding in subjects with metabolic syndrome/obesity, hypertension, kidney disease. Recent blood pressures (BPs) had been 1. Hg and 1. 75/8. 8 mm Hg and was 1. Hg when seen in the hypertension clinic. Creatinine was 1. L (normal 0. 7–1. L) and uric acid was 4. L (normal 3. 4–7. L). Medications included atenolol 5. The patient was hesitant to retry a diuretic, but was persuaded to take hydrochlorothiazide 1. Follow- up BPs were 1. Hg/6. 6 to 7. 2 mm Hg without recurrence of gout 6 months later. Case 2: A 4. 3- year- old man was seen in our hypertension clinic because of uncontrolled BP. Antihypertensive medication was introduced to the patient in his 3. Podagra and gouty flares of the right instep occurred once or twice yearly and were almost always preceded by eating mong beans. BP at the time of evaluation was 1. Hg, with a creatinine value of 1. L and uric acid value of 9. L. His medications included lisinopril 4.
Allopurinol 3. 00 mg daily and hydrochlorothiazide 1. BP of 1. 30/8. 2 mm Hg and a uric acid value of 6. L. Hypertension and Gout Are Overlapping Diseases. The prevalence of gout has been increasing and the Third National Health and Nutrition Examination Survey (NHANES III) estimated that more than 5 million Americans were affected in 1. The incidence of gout also increases with advancing age similar to the age- related occurrence of hypertension. Hypertension alone is a predictor of gout, along with the additional risk factors of obesity, serum uric acid level, alcohol intake, and the use of thiazide and loop diuretics in additive fashion. Since gout is a common disease, affecting 1% of men in Western countries,2 its management will occasionally overlap with a primary care practice of patients with hypertension. Although there are many antihypertensive medication classes in addition to diuretics from which to choose, 1. Moreover, the concordant experience of two large university clinics has been that the most common cause of refractory hypertension is the lack of diuretic therapy. Therefore, as in these two cases, gout will occasionally occur in patients with resistant hypertension who need diuretic therapy. What Is the Relationship Between Hyperuricemia and Clinical Gout? Based on 3. 0,1. 47 human years of prospective observation in the Prospective Normative Aging Study,3 incident rates of acute gouty arthropathy were highly related to the most recent serum urate level. However, incident rates were only 7% per year for the highest urate levels . During 5 years of prospective follow- up, 7. For those participants with urate levels of 7. L to 8. 9 mg/d. L, the cumulative incidence of gout after 5 years was only 3%. Because all of the participants in this aging study were men, these incidence rates were probably higher than the general population due to the male: female ratio of clinical gout ranging from 7: 1 to 9: 1. Cumulative incidence of gouty arthritis by prior urate levels. The numbers refer to the number of examination intervals for each group. Reprinted with permission from Campion. What Effect Does Thiazide Have on Uric Acid Levels and Gout? The Hypertension Detection and Follow- up Program (HDFP) randomized patients to more intensive “stepped care” therapy vs usual or “referred care.” Step 1 of the HDFP drug protocol was chlorthalidone 5. Although baseline uric acid levels were related to renal function, increases in uric acid on chlorthalidone were the same with serum creatinine levels < 1. The primary conclusion of this analysis is that discontinuation of chlorthalidone due to clinical gout was rare, occurring in 1. Although infrequent, diuretic use is an important risk factor for gout in observational studies. However, diuretics may be less important in this regard than other risk factors. In the Health Professionals Follow- up Study,9 the multivariate relative risks of gout were 2. The uricosuric mechanism has been attributed to inhibition of urate transporter 1, thereby interfering with urate reabsorption across the apical luminal membrane of the proximal renal tubule. The short- term time course of < 6 hours for the uricosuric effect implies that this property belongs to the parent compound rather than its metabolites. Studies examining uric acid lowering related to the dosage of losartan are inconsistent. In one study, decreases in serum uric acid followed a dose- dependent pattern from 0. L to 1. 3. 3 mg/d. L over a losartan dose range from 2. Another study showed that losartan dose escalation from 5. Other studies have examined the urate- balancing effects of adding losartan to hydrochlorothiazide. Uricosuria occurring with losartan in patients treated with hydrochlorothiazide occurs in the absence of risk for precipitating urate nephropathy. There is a significant decrease in thiazide- induced hyperuricemia proportional to losartan dosing, but not enough to completely reverse all of the thiazide- related augmentation of serum uric acid (Figure 2). Changes in serum uric acid values with different doses of losartan in hypertensive patients. Serum uric acid values were obtained in the placebo period, following 4 weeks of monotherapy with 2. HCTZ), and after 1. Reprinted with permission from Soffer et al. It is uncertain whether the modest and transient uric acid–lowering effect of losartan is enough to translate into benefit- reducing gouty attacks, and clinical end point studies are lacking. Missing a single daily dose of losartan would lead to a gap in protection. Alhough losartan and probenecid share similar uric acid–lowering mechanisms, losartan is less potent and should not be considered for reliable long- term antihyperuricemic therapy. Other drugs with incidental uricosuric effects include ascorbic acid, calcitonin, and fenofibrate. Is Uric Acid a Cardiovascular Risk Factor? Does Reducing Uric Acid Decrease BP in Patients With Hypertension? Many studies that generally use multivariate analyses have associated a high relative risk of hypertension with hyperuricemia, but whether hyperuricemia is truly an independent risk factor is controversial. The Framingham Heart Study concluded that uric acid was not independently associated with cardiovascular risk, and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure did not list uric acid as a cardiovascular risk predictor. Because of the high correlation of pediatric hyperuricemia with hypertension, it has been hypothesized that uric acid may be one of several triggers for renal vasoconstriction as an initial phase in the development of essential hypertension. However, prevention of hyperuricemia has not been shown to forestall hypertension. An analysis of the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study. However, a better explanation of the treatment difference between losartan and atenolol favoring losartan in the LIFE trial probably was the lack of comparable reduction of central aortic pressure with atenolol. Although a small short- term study showed minimal reduction of BP within the normal range in patients with hyperuricemia treated with allopurinol, treatment of hyperuricemia has not been shown to reduce BP in patients with hypertension. Allopurinol is not a very favorable drug outside of its indication for prophylactic antihyperuricemic therapy because, although rare, its toxicities include a severe hypersensitivity syndrome. What Are the Options When a Hypertensive Patient Taking Thiazide Develops Gout? These two cases illustrate that patients with long histories of recurrent gout and hypertension resistant to . Lowering serum uric levels to between 4. L and 6. 6 mg/d. L with antihyperuricemic agents lowers recurrence of gouty arthropathy in predisposed patients by 3. Another common scenario is a patient with controlled hypertension taking thiazide who has an attack of acute gouty arthritis. Intercritical gout, the term applied to the periods between gouty attacks, may last years. In one series, 6. Because of the long time interval between gouty attacks, which may be mild and readily responsive to therapy, and the fact that maintenance of BP control may not be readily achieved with an antihypertensive drug substitution for thiazide, cessation of thiazide is a consideration but not mandatory depending on the clinical context. Reduction of the dose of thiazide rather than discontinuation is also an option because drug- related hyperuricemia is dose- related. Spironolactone might be a good add- on in such situations. A small well- done study showed only a modest increase in serum uric acid in patients receiving 1. Therefore, in a patient with resistant hypertension in whom a decision to reduce thiazide leads to loss of control, 1. A reasonable strategy for dealing with an attack of gout for a patient taking thiazide for hypertension is treatment with 1 or 2 days of a nonsteroidal anti- inflammatory drug or colchicine, while continuing thiazide therapy pending early follow- up. Uric acid level obtained during an acute attack may be spuriously low. Depending on the severity of the gouty attack, the level of uric acid following resolution of the episode, and the degree of difficulty in achieving BP control, treatment options listed in the Table can be discussed in calmer surroundings outside of the emergency department or urgent care clinic where gouty flares are often evaluated.
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