Background & Aims: Non-alcoholic fatty liver disease (NAFLD) can develop in individuals who are not overweight. Whether lean persons with NAFLD have lower mortality and lower incidence of cirrhosis, cardiovascular diseases (CVD), diabetes mellitus (DM) and cancer than overweight/obese persons with NAFLD remains inconclusive. We compared mortality and incidence of cirrhosis, CVD, DM and cancer between lean versus non-lean persons with NAFLD.Methods: This is a retrospective study of adults with NAFLD in a single centre from 2012 to 2021. Primary outcomes were mortality and new diagnosis of cirrhosis, CVD, DM and cancer. Outcomes were modelled using competing risk analysis and Cox proportional hazards regression analysis.Results: A total of 18,594 and 13,420 patients were identified for cross-sectional and longitudinal analysis respectively: approximately 11% lean, 25% overweight, 28% class 1 obesity and 35% class 2-3 obesity. The median age was 51.0 years, 54.6% were women. The median follow-up was 49.3 months. Lean patients had lower prevalence of metabolic diseases at baseline and lower incidence of cirrhosis and DM than non-lean patients and no difference in CVD, any cancer or obesity-related cancer during follow-up. However, lean patients had significantly higher mortality with incidence per 1000 person-years of 16.67, 10.11, 7.37 and 8.99, respectively, in lean, overweight, obesity class 1 and obesity class 2-3 groups respectively.Conclusions: Lean patients with NAFLD had higher mortality despite lower incidence of cirrhosis and DM, and similar incidence of CVD and cancer and merit similar if not more attention as non-lean patients with NAFLD.| 1015 WIJARNPREECHA et al. | INTRODUC TI ONNon-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, affecting 25% of the population worldwide, and its clinical burden is expected to rise. 1 NAFLD is strongly associated with obesity and its comorbidities but can also develop in individuals who are not overweight ('lean NAFLD'). 2 The prevalence of NAFLD among lean individuals in the general population is 10%-20% with most studies reported from Asian countries, and the highest prevalence reported in Mexico (37%). [3][4][5][6] NAFLD is associated with a wide spectrum of extrahepatic diseases, such as cardiovascular diseases (CVD), metabolic diseases (diabetes mellitus [DM], hypertension, dyslipidaemia), chronic kidney diseases (CKD) or cancers. 7,8 Several cross-sectional studies have evaluated prevalence of hepatic and extra-hepatic diseases among lean versus obese individuals with NAFLD. A cross-sectional analysis of the TARGET-NASH study cohort with 3386 NAFLD patients in the United States found a lower prevalence of cirrhosis, DM and CVD in lean individuals compared to overweight/obese individuals. 2 Another study from Austria with 4091 NAFLD participants had similar findings with lower prevalence of metabolic diseases (DM, metabolic syndrome, hypertension, dyslipidaemia) and lower Framingham risk score for CVD but no significant differen...
Background: While hypertension is a modifiable risk factor of Alzheimer's disease and related dementias (ADRD), limited studies have been conducted on the effectiveness of antihypertensive medications (AHMs) in altering the progression from mild cognitive impairment (MCI) to ADRD; similarly, few studies have assessed drug-drug interactions of AHMs with drugs targeted to modify other risk factors of ADRD such as type Ⅱ diabetes and hypercholesterolemia. Method: 128,683 unique hypertensive patients with MCI on US-based Optum claims data were identified. Diuretics, beta blockers (BBs), calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACE inhibitors), and angiotensin II receptor antagonists (ARBs) were identified as five major AHM classes. Baseline characteristics were compared. Cox proportional hazards (PH) models were used to study the association between specific AHM exposure and the progression from MCI to ADRD while controlling for demographic variables, comorbidities, and the use of Statins and Metformin. To examine the association of AHM-Statin or AHM-Metformin interaction with ADRD progression, we also investigated models controlling for the aforementioned confounders, as well as drug-drug interactions. Result: The study included 100,678 patients who were taking at least one class of AHM and 28,005 who were not taking any AHMs during the study period. AHM users had a higher incidence of comorbidities (all P≤0.039) and consumption of Metformin and Statins (both P<0.001) compared to non-users. Users of each major AHM class showed significantly lower risk of developing ADRD compared to non-users of that specific drug class (adjusted hazard ratio (aHR): 0.96-0.98; all P≤0.048). Within patients on monotherapy (using only one AHM drug), no specific AHM class had significantly lower risk of ADRD diagnosis compared to other AHM drug classes (aHR: 0.97-1.11; all P≥0.053). Use of Diuretics or CCBs in combination with Metformin consumption (aHR: 0.89, 0.91, respectively) showed lower risk of MCI to ADRD progression than use without Metformin consumption (aHR: 0.97, 0.98, respectively), whereas use of any of the five major AHMs with Statin consumption (aHR: 0.91-0.94) all showed lower risk than without Statin consumption (aHR: 0.98-1.04). Conclusion: All five major AHM classes showed a protective effect against ADRD progression among hypertensive patients with MCI. Also, certain combinations of AHMs with Metformin or Statins showed a stronger protective effect compared to AHMs alone, and some drug-drug interactions of AHMMetformin or AHM-Statin also showed protective effects against progression from MCI to ADRD.
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