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Primary Aldosteronism Common in Patients With Type 2 Diabetes and Resistant Hypertension

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Primary Aldosteronism Common in Patients With Type 2 Diabetes and Resistant Hypertension CME


News Author: Laurie Barclay, MD

CME Author: D?sir?e Lie, MD, MSEd


Release Date: July 3, 2007; Valid for credit through July 3, 2008

Credits Available


Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)? for physicians;

Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians


July 3, 2007 ? In patients with type 2 diabetes and resistant hypertension, primary aldosteronism has a prevalence of 14%, according to the results of a study published in the July issue of Diabetes Care. The authors recommend screening for aldosteronism in these patients who are taking 3 or more antihypertensive drugs.


"Despite the high prevalence of hypertension in patients with type 2 diabetes, the prevalence of primary aldosteronism in this population has not been determined," write Guillermo E. Umpierrez, MD, from Emory University School of Medicine in Atlanta, Georgia, and colleagues. "Primary aldosteronism was previously believed to account for


In this study, 100 participants with type 2 diabetes and resistant hypertension, defined as blood pressure greater than 140/90 mm Hg despite treatment with at least 3 antihypertensive agents, were screened for primary aldosteronism by measuring the PAC/PRA ratio. Of the 100 participants, 93 were African Americans.


In participants with a PAC/PRA ratio greater than 30 ng/mL/hour, confirmatory salt load testing was performed. Primary aldosteronism was defined as a 24-hour urine aldosterone level of 12 ?g or greater during the third day of the oral salt load or a PAC of 5 ng/dL or greater after the 4-hour intravenous saline load.


The PAC/PRA ratio was greater than 30 ng/mL/hour in 34 participants, and there was a confirmed diagnosis of primary aldosteronism for 14 participants (14%; 95% confidence interval, 7.2 - 20.8). Participants with and without primary aldosteronism did not differ in age, glycemic control, and number of antihypertensive drugs.


Compared with patients without primary aldosteronism, those with primary aldosteronism had lower serum potassium levels (3.7 ? 0.4 vs 4.0 ? 0.4 mmol/L; P = .012), higher PACs (15.6 ? 8 vs 9.1 ? 6 ng/dL; P = .0016), and higher PAC/PRA ratios (98 ? 74 vs 21 ? 30 ng/mL/hour; P


"Primary aldosteronism is common in diabetic patients with resistant hypertension, with a prevalence of 14%," the authors write. "Our results indicate that diabetic subjects with poorly controlled hypertension who are taking ? 3 antihypertensive drugs should be screened for primary aldosteronism."


Study limitations include a relatively small number of subjects, most subjects being African American, and the lack of a control group without diabetes.


"These results are of great clinical importance because patients with primary aldosteronism have a high incidence of renal and cardiovascular complications and increased mortality and because aldosterone blockade can ameliorate renal and cardiovascular complications in patients with hypertension and with primary aldosteronism," the authors conclude.


Dr. Umpierrez is supported by research grants from the American Diabetes Association, the American Heart Association, and the National Institutes of Health and by a General Clinical Research Center Grant. The costs of publication of the original article were defrayed in part by the payment of page charges, which mandated its being marked "advertisement."


Diabetes Care. 2007;30:1699-1703.


Clinical Context


According to the authors of the current study, 20 million people in the United States have diabetes and another 50 million have hypertension, and diabetes and hypertension coexist in 40% to 60% of patients with type 2 diabetes with a 1.5- to 3-times increase in prevalence vs patients without diabetes. Furthermore, 50% of patients with diabetes have hypertension at the time of diagnosis. The American Diabetes Association has recommended a blood pressure goal of 130/80 mm Hg or lower for adults with diabetes, and 10% to 30% of individuals with diabetes are believed to have resistant hypertension.


Rigorous blood pressure control in patients with diabetes reduces the risk for microvascular and macrovascular complications, according to the authors. The incidence of primary aldosteronism as a cause of secondary hypertension has increased 5 to 10 times, accounting for 5% to 32% of the population with resistant hypertension, but it is uncertain what proportion of patients with diabetes and resistant hypertension have primary aldosteronism.


This is a descriptive study of 100 consecutive patients with type 2 diabetes and resistant hypertension to describe the prevalence of primary aldosteronism in this population.


Study Highlights


* Included were 100 consecutive patients aged 18 to 75 years with type 2 diabetes for more than 3 months and treated for hypertension with at least 3 antihypertensive medications.


* Resistant hypertension was defined as blood pressure greater than 140/90 mm Hg despite the use of 3 or more antihypertensive agents.


* Excluded were those treated with spironolactone or eplerenone; those with glycated hemoglobin value greater than 9%, severe uncontrolled hypertension (blood pressure > 180/110 mm Hg), a history of heart failure, angina, a serum creatinine level greater than 1.8 mg/dL, hepatic disease, Cushing's disease, hyperthyroidism, or pheochromocytoma; and those who were pregnant or lactating.


* Patients were screened for primary aldosteronism while taking their usual medications, because stopping blood pressure medications was considered unethical.


* Blood samples were drawn in the morning after 30 minutes of rest in the sitting position.


* Patients with serum potassium levels of less than 3.5 mmol/L received KCl (40 mEq) daily for 1 week and were rescreened once the potassium level was at least 3.5 mmol/L.


* Screening studies included measurement of PAC and PRA and the calculation of the PAC/PRA ratio.


* Patients with hypertension and a PAC/PRA ratio greater than 30 ng/mL/hour underwent further studies to confirm a diagnosis of primary aldosteronism.


* Salt loading was used to confirm the diagnosis.


* Urinary aldosterone was measured 3 days after a salt load or PAC was measured after an intravenous salt load of 2 L of 0.9% saline infused for 4 hours at 500 mL/hour.


* Primary aldosteronism was diagnosed if the 24-hour urinary aldosterone concentration was 12 ?g or greater during the third day of salt load or if PAC was 5.0 ng/dL or greater after the intravenous load.


* 93 patients were black, 5 were white, 1 was Hispanic, and 1 was Native American.


* Mean age was 59 years, mean duration of diabetes was 8.9 years, mean duration of hypertension was 16 years, and mean body mass index was 34.4 kg/m2 with 75% having a body mass index greater than 30 kg/m2.


* The mean number of antihypertensive agents taken was 3.7.


* 98% were taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 92% were taking a diuretic agent, 73% were taking a ?-blocker, 62% were talking a calcium channel blocker, and 31% were taking an ?-blocker.


* Mean potassium level was 4.0 mmol/L with 15 subjects having levels below 3.5 mmol/L.


* 34% had an increased PAC/PRA ratio and received additional testing.


* Primary aldosteronism was diagnosed in 14% of patients.


* There were no differences in age, years of hypertension, years of diabetes, body mass index, blood pressure, glycated hemoglobin level, or numbers or types of antihypertensive agents used between those with and without primary aldosteronism.


* Mean systolic and diastolic blood pressures were 157 and 93 mm Hg in those with primary aldosteronism and 158 and 89 mm Hg, respectively, in those without.


* Those with primary aldosteronism had a lower potassium level (3.7 vs 4.0 mmol/L), lower serum creatinine level (0.9 vs 1.0 mg/dL), a higher PAC, a lower PRA, and higher PAC/PRA ratio vs those without primary aldosteronism.

* Of those with resistant hypertension, 55% had suppressed PRA or salt-sensitive hypertension.


* The authors concluded that patients with diabetes and poorly controlled hypertension should be screened for primary aldosteronism using the PAC/PRA ratio followed by salt-suppression testing in those with a positive ratio.


Pearls for Practice


* Resistant hypertension in patients with type 2 diabetes is defined as a persistent blood pressure of 140/90 mm Hg or higher despite treatment with at least 3 antihypertensive agents.


* The prevalence of primary aldosteronism among patients with type 2 diabetes with resistant hypertension is 14%.

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