Prevalence of familial hypercholesterolemia in a country-wide laboratory network in Pakistan: 10-year data from 988, 306 patients.

INTRODUCTION: Familial hypercholesterolemia (FH) is a modifiable risk factor for premature coronary heart disease but is poorly diagnosed and treated. We leveraged a large laboratory network in Pakistan to study the prevalence, gender and geographic distribution of FH. METHODOLOGY: Data were curated from the Aga Khan University Hospital clinical laboratories, which comprises of 289 laboratories and collection points spread over 94 districts. Clinically ordered lipid profiles from 1st January 2009 to 30th June 2018 were included and data on 1,542,281 LDL-C values was extracted. We used the Make Early Diagnosis to Prevent Early Death (MEDPED) criteria to classify patients as FH and reported data on patients with low-density liporotein -cholesterol (LDL-C) ≥ 190 mg/dL. FH cases were also examined by their spatial distribution. RESULTS: After applying exclusions, the final sample included 988,306 unique individuals, of which 24,273 individuals (1:40) had LDL-C values of ≥190 mg/dL. Based on the MEDPED criteria, 2416 individuals (1:409) had FH. FH prevalence was highest in individuals 10-19 years (1:40) and decreased as the patient age increased. Among individuals ≥40 years, the prevalence of FH was higher for females compared with males (1:755 vs 1:1037, p < 0.001). Median LDL-C for the overall population was 112 mg/dL (IQR = 88-136 mg/dL). The highest prevalence after removing outliers was observed in Rajan Pur district (1.23% [0.70-2.10%]) in Punjab province, followed by Mardan (1.18% [0.80-1.70%]) in Khyber Pakhtunkhwa province, and Okara (0.99% [0.50-1.80%]) in Punjab province. CONCLUSION: There is high prevalence of actionable LDL-C values in lipid samples across a large network of laboratories in Pakistan. Variable FH prevalence across geographic locations in Pakistan may need to be explored at the population level for intervention and management of contributory factors. Efforts at early diagnosis and treatment of FH are urgently needed.

Clinical outcomes of immunomodulatory therapies in the management of COVID-19: A tertiary-care experience from Pakistan.

The pharmacological management of COVID-19 has evolved significantly and various immunomodulatory agents have been repurposed. However, the clinical efficacy has been variable and a search for cure for COVID-19 continues. A retrospective cohort study was conducted on 916 patients hospitalized with polymerase chain reaction (PCR)-confirmed COVID-19 between February 2020 and October 2020 at a tertiary care academic medical center in Karachi, Pakistan. The median age was 57 years (interquartile range (IQR) 46-66 years). The most common medications administered were Methylprednisolone (65.83%), Azithromycin (50.66%), and Dexamethasone (46.6%). Majority of the patients (70%) had at least two or more medications used in combination and the most frequent combination was methylprednisolone with azithromycin. Overall in-hospital mortality was 13.65% of patients. Mortality was found to be independently associated with age greater than or equal to 60 years (OR = 4.98; 95%CI: 2.78-8.91), critical illness on admission (OR = 13.75; 95%CI: 7.27-25.99), use of hydrocortisone (OR = 12.56; 95%CI: 6.93-22.7), Ferritin> = 1500(OR = 2.07; 95%CI: 1.18-3.62), Creatinine(OR = 2.33; 95%CI: 1.31-4.14) and D-Dimer> = 1.5 (OR = 2.27; 95%CI: 1.26-4.07). None of the medications whether used as monotherapy or in combination were found to have a mortality benefit. Our study highlights the desperate need for an effective drug for the management of critical COVID-19 which necessitates usage of multiple drug combinations in patients particularly Azithromycin which has long term implications for antibiotic resistance particularly in low-middle income countries.