There have been several clinical studies examining the factors associated with cardiovascular disease (CVD) in patients with primary aldosteronism (PA); however, their results have left it unclear whether CVD is affected by the plasma aldosterone concentration or hypokalemia. We assessed the PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) and compared the prevalence of CVD among patients with PA with that among age-, sex-, and blood pressure-matched essential hypertension patients and participants with hypertension in a general population cohort. We also performed binary logistic regression analysis to determine which parameters significantly increased the odds ratio for CVD. Of the 2582 patients with PA studied, the prevalence of CVD, including stroke (cerebral infarction, cerebral hemorrhage, or subarachnoid hemorrhage), ischemic heart disease (myocardial infarction or angina pectoris), and heart failure, was 9.4% (stroke, 7.4%; ischemic heart disease, 2.1%; and heart failure, 0.6%). The prevalence of CVD, especially stroke, was higher among the patients with PA than those with essential hypertension/hypertension. Hypokalemia (K ≤3.5 mEq/L) and the unilateral subtype significantly increased adjusted odds ratios for CVD. Although aldosterone levels were not linearly related to the adjusted odds ratio for CVD, patients with plasma aldosterone concentrations ≥125 pg/mL had significantly higher adjusted odds ratios for CVD than those with plasma aldosterone concentrations <125 pg/mL. Thus, patients with PA seem to be at a higher risk of developing CVD than patients with essential hypertension. Moreover, patients with PA presenting with hypokalemia, the unilateral subtype, or plasma aldosterone concentration ≥125 pg/mL are at a greater risk of CVD and have a greater need for PA-specific treatments than others.

To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan. RESEARCH DESIGN AND METHODS The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA 1c ] ‡6.5% [ ‡48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia (<3.5 mEq/L), suspected subclinical hypercortisolism (SH; serum cortisol ‡1.8 mg/dL after 1-mg dexamethasone suppression test), and PA laterality on the prevalence of diabetes or prediabetes (5.7% £ HbA 1c <6.5% [39 mmol/mol £ HbA 1c <48 mmol/mol]) were examined. RESULTS Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30-69 years. Logistic regression or x 2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA 1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA. CONCLUSIONS Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA.

Aims/IntroductionTo analyze the association between the duration of diabetes and selection of diabetes therapy in a large database of Japanese patients with type 2 diabetes.Materials and MethodsWe used the data of 5,844 patients with type 2 diabetes to evaluate the association between the duration of diabetes and types of diabetes therapy. The logistic regression model was used to analyze the association between duration of diabetes and selection of diabetes therapy, and restricted cubic spline curves were used to represent the schematic association.ResultsOverall, clinical characteristics of the patients were women, 39.9%; mean age, 61.4 years; median duration of diabetes, 9 years; mean glycated hemoglobin, 7.4% (57.0 mmol/mol); and mean body mass index, 24.5 kg/m2. Compared with the first quartile of diabetes duration, the multivariable‐adjusted odds of any antidiabetic therapy (oral hypoglycemic agents or insulin) for the second, third and fourth quartiles were 2.17 (95% confidence interval [CI] 1.68–2.80; 3.39, 95% CI 2.53–4.54; 4.99, 95% CI 3.64–6.84), respectively (P for trend <0.001), and these associations were attenuated after adjusting possible confounders. Furthermore, those of insulin therapy were 1.48 (95% CI 1.20–1.84; 2.16, 95% CI 1.77–2.64; 4.94, 95% CI 4.04–6.04), respectively (P for trend <0.001). Schematic representation of restricted cubic spline curves analysis showed that a longer duration of diabetes was linearly associated with the odds of insulin therapy.ConclusionsObtained data showed that a longer duration of diabetes required complex diabetes drug regimens to be introduced to patients with type 2 diabetes.

Low and high serum uric levels, independent of possible confounders, were associated with a subsequent risk of progression, not development, in albuminuria in type 2 diabetes patients. Therefore, serum uric acid levels may be useful for predicting the future risk of progression of microalbuminuria.

ObjectivesThe aim of this study was to investigate the impact of adrenal venous sampling (AVS) lateralization cutoffs on surgical outcomes.Patients and MethodsCosyntropin-stimulated AVS was used to guide surgical management of 377 patients with primary aldosteronism (PA) who were evaluated 6 months after surgery.Main Outcome MeasuresThe proportion of patients that achieved clinical benefit and complete biochemical success based on the AVS aldosterone lateralization index (LI) was determined.ResultsClinical benefit was achieved in 29 of 47 patients with an LI between 2 and 4, in 66 of 101 with an LI between 4 and 10, and in 158 of 203 with an LI > 10 (P < 0.01 for trend). Complete biochemical success was achieved in 27 of 42 with an LI between 2 and 4, in 60 of 76 with an LI between 4 and 10, and in 127 of 155 with an LI > 10 (P = 0.024 for trend). After adjustment for confounders and using those patients with an LI between 2 and 4 as a reference, a clinical benefit was associated only with those with an LI > 10 (OR, 2.30; 95% CI, 1.03 to 5.16), whereas complete biochemical success was associated with those with an LI between 4 and 10 (OR, 2.83; 95% CI, 1.14 to 7.01) or LI > 10 (OR, 3.55; 95% CI, 1.47 to 8.55).ConclusionsDifference of clinical outcome was relatively small when strict LI diagnostic threshold was used; biochemical cure was sufficiently achieved when an LI > 4 was used. Our study by standardized outcome measures validated that an LI > 4 may be appropriate for determining unilateral disease in PA.

Adrenalectomy contributes to biochemical improvement in elderly patients if determined in accordance with AVS. The treatment strategy should be determined considering the high postoperative incidence of persistent hypertension and hyperkalemia in elderly patients with a long history of hypertension or renal impairment in those with reduced renal function.

Primary aldosteronism patients aged <35 years with hypokalaemia and elevation of aldosterone and unilateral disease on adrenal CT could be spared AVS.

OBJECTIVETo assess the correlations between serum bilirubin levels and diabetic nephropathy development and progression in type 2 diabetic patients. RESEARCH DESIGN AND METHODSLongitudinal data were obtained from 2,511 type 2 diabetic patients registered in a Japanese diabetes registry. To assess the independent correlations between serum bilirubin levels and either the development or progression of diabetic nephropathy, we used logistic regression analysis adjusted for potential confounders. RESULTSThe median follow-up period was 503.4 days (range 238-777). The mean patient age, BMI, and HbA 1c level was 65.2 years, 24.7 kg/m 2 , and 7.5% (58.5 mmol/mol), respectively. Baseline serum bilirubin levels were significantly associated with the urinary albumin-creatinine ratio at baseline (P < 0.001) and 1 year after registration (P < 0.001). Multivariable adjusted odds ratios for progression from microalbuminuria to macroalbuminuria for the second, third, and fourth quartile of serum bilirubin levels were 0.89 (95% CI 0.49-1.58), 0.93 (0.47-1.83), and 0.33 (0.13-0.84), respectively, showing a statistically significant linear trend across categories (P = 0.032). However, this trend disappeared after adjustment for hemoglobin levels. CONCLUSIONSSerum bilirubin levels were associated with diabetic nephropathy progression in type 2 diabetic patients independent of possible confounders. Serum bilirubin levels might be the link in the correlation between hemoglobin levels and nephropathy progression.