DESIGN: We instituted a questionnaire-based survey to specialists managing PA, assessing the availability and affordability of investigations and treatment. Population and income status data were taken from the national census and registries.

RESULTS: Nine ASEAN country members (48 respondents) participated. While screening with aldosterone-renin-ratio is performed in all countries, confirmatory testing is routinely performed in only six countries due to lack of facilities and local assays, and cost constraint. Assays are only locally available in four countries, and some centers have a test turnaround time exceeding three weeks. In seven countries (combined population of 442 million), adrenal vein sampling (AVS) is not routinely performed due to insufficient radiological facilities or trained personnel, and cost constraint. Most patients have access to adrenalectomy and medications. In six countries, the cost of AVS and adrenalectomy combined is >30% of its annual gross domestic product per capita. While most patients had access to spironolactone, it was not universally affordable.

OBJECTIVE: To discover genetic variants associated with HbA1c level in nondiabetic Malay individuals.

DESIGN AND PARTICIPANTS: We conducted a genome-wide association study (GWAS) analysis for HbA1c using 2 Malay studies, the Singapore Malay Eye Study (SiMES, N = 1721 on GWAS array) and the Living Biobank study (N = 983 on GWAS array and whole-exome sequenced). We built a Malay-specific reference panel to impute ethnic-specific variants and validate the associations with HbA1c at ethnic-specific variants.

METHODS: Individuals from the HyperPATH cohort were assessed for blood pressure and hormone levels after controlled low and liberal sodium diets. Black and White individuals with genotype data for LSD1 (rs587168) and STRN diplotype (rs888083 and rs6744560) were included.

RESULTS: 127 Black individuals were categorized: 1) Higher Risk: individuals who carried 1 or 2 risk alleles from both LSD1 and STRN and 2) Lower Risk: individuals who did not meet these criteria. In multivariable analysis, SSBP was higher among the Higher Risk versus the Lower Risk groups (18.9 ± 1.8 mmHg vs 10.8 ± 1.6 mmHg, p-value < 0.0001). Among hypertensive individuals, SSBP was 22.9 ± 2.5 mmHg vs 12.9 ± 2.1 mmHg for the Higher Risk vs Lower Risk groups, respectively (p-value <0.0001). These results were confirmed in a second cohort of 37 Black individuals (p-value=0.029). In 396 White individuals, no differences were observed.

OBJECTIVE: We hypothesized that Cav1.3 blockade by cinnarizine may achieve similar, or greater, reduction in aldosterone secretion than nonselective Cav1.2/1.3 blockade by nifedipine.

METHODS: Separate wells of angiotensin II-stimulated HAC15 cells were treated with either cinnarizine (1-30 μM) or nifedipine (1-100 μM). Aldosterone concentrations were measured in culture medium; RNA extraction and quantitative polymerase chain reaction were performed to evaluate CYP11B2 expression. A prospective, open-label, crossover study was conducted of 15 adults with PA, treated with 2 weeks of cinnarizine 30 mg 3 times a day or nifedipine extended release 60 mg daily, separated by a 2-week washout. The hierarchical primary outcome was change in aldosterone-to-renin ratio (ARR), urinary tetrahydroaldosterone (THA), and plasma aldosterone concentration (PAC). Blood pressure change was a secondary outcome. Parametric analysis was undertaken on log-transformed data. (ClinicalTrials.gov: NCT05686993).

RESULTS: Both drugs reduced aldosterone concentrations and CYP11B2 expression in vitro. Mean changes ± SEM in fold change of aldosterone concentrations and CYP11B2 were -0.47 ± 0.05 and -0.56 ± 0.07, respectively, with cinnarizine 30 μM and -0.59 ± 0.05 and -0.78 ± 0.07 with nifedipine 100 μM. In the clinical crossover trial, ARR was reduced by nifedipine but not cinnarizine (F = 3.25; P = .047); PAC rose with both drugs (F = 4.77; P = .013), but urinary THA was unchanged.