Congenital heart disease (CHD) is an umbrella term describing a variety of structural cardiac malformations at birth. CHD affects approximately 1 % of live births, generating a large adult population with these abnormalities. Pulmonary hypertension (PH) in patients with adult CHD is heterogeneous, based on the type of defect and associated conditions, but is a known cause of adverse outcome. We retrieved death certificate data from the CDC-WONDER database using ICD codes (I27.0, I27.2, I27.8, and I27.9., and Q20-26). Crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated. Temporal trends were examined using the annual percent change (APC) and average annual percent change (AAPC) determined by Joinpoint regression. From 1999 to 2020, an overall declining pattern was observed in the mortality rate. Men and women with congenital heart disease and pulmonary hypertension in the U.S. experienced a statistically significant decline in mortality rates. In terms of races, among White individuals, the decline was the most pronounced. All four U.S. census regions experienced statistically significant declines in mortality due to pulmonary hypertension among individuals with congenital heart disease. The rate of decline was steeper in rural areas compared to urban ones. This study highlights that previously implemented targeted interventions significantly contributed to the reduction of mortality amongst patiemnts with congenital heart disease and pulmonary hypertension in the U.S. Still improvements are required in certain areas, including female gender, Hispanic or Latino, and the Northeast and West regions.

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, while hypertensive heart disease (HHD) is a major cardiovascular condition linked to chronic hypertension (HTN). HTN is common among patients with AD, significantly impacting mortality. This study explores trends in HHD-related mortality among patients with AD in the US from 1999 to 2020, utilizing the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database. Methods: Data from the CDC WONDER database were used to extract mortality information for individuals aged ≥65 years, with AD and HHD as the underlying or contributing causes of death. Mortality rates were analyzed by age, sex, race/ethnicity, urban–rural classification, and region. Both crude- and age-adjusted mortality rates (AAMRs) were calculated. Joinpoint regression was employed to identify significant trends and changes in mortality over time. Results: HHD-associated mortality among patients with AD showed a significant upward trend, with deaths rising from 710 in 1999 to 3263 in 2020. The AAMR increased from 2.08 per 100 000 in 1999 to 6.26 per 100 000 in 2020, a threefold increase. Female patients had higher mortality rates than males throughout the study period. The highest mortality rates were observed in the age group of 85+ years, with notable regional disparities, particularly in the South and Midwest. The COVID-19 pandemic in 2020 contributed to a marked spike in mortality. Conclusion: A concerning rise in HHD-related mortality among patients with AD, particularly in the last decade is observed. Significant disparities exist across demographic groups and regions. These findings highlight the need for public health interventions and policies to address the dual burden of AD and HHD.

Aims: Novel drugs that target apoC‐III in lipoprotein metabolism to reduce plasma triglycerides are currently under development. Olezarsen, a drug similar to its predecessor, volanesorsen, is in Phase 3 trials. A meta‐analysis of RCTs was done to study its effect on hypertriglyceridemia. Material and Methods: Screening was done on PubMed, Embase, Scopus, and the Cochrane Library from inception to August 2024. We used Review Manager (Version 5.4) for statistical analysis. Subgroups of olezarsen at doses of 10, 50, and 80 mg were made. Continuous outcomes were reported as mean differences with 95% CIs. Adverse events were reported using risk ratios and 95% CIs. The risk of bias was analyzed using the Cochrane risk of bias tool. Results: Four RCTs with 374 participants, 278 in intervention and 96 placebo controls, were included. At all doses of olezarsen, a significant reduction in fasting triglyceride levels (MD: 45.69; 95% CI: 35.84, 55.54; p < 0.00001) was seen. This was most pronounced at 80 mg dose (MD: 51.98 95% CI: 43.06, 60.90; p < 0.00001). A reduction in apoC‐III (MD: 58.77; 95% CI: 35.94, 81.61; p < 0.00001) and an increase in HDL (MD: 0.21; 95% CI: 0.04, 0.37; p = 0.01) were also observed. No significant effect was observed on LDL levels (MD: −0.13; 95% CI: −0.40, 0.14; p = 0.34). Overall, no significant adverse effects were seen compared to placebo (RR: 1.42; 95% CI: 0.66, 3.05; p = 0.37). Conclusion: Olezarsen showed remarkable efficacy in lowering triglycerides, with a dose‐dependent effect, while significantly increasing HDL levels and reducing apoC‐III. Its safety profile is commendable. Although it performed well compared to volanesorsen, inconsistencies in LDL reduction and heterogeneity in some groups warrant further large‐scale RCTs to better assess its safety and efficacy. Clinical decisions should be tailored to individual patient profiles, as hypertriglyceridemia management may vary on a case‐to‐case basis.