It is Time to Screen for Homozygous Familial Hypercholesterolemia in the United States.

Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately one in 300,000 people. The disorder is characterized by extremely high, life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth, leading to significant premature cardiovascular morbidity and mortality, if left untreated. Homozygous familial hypercholesterolemia is severely underdiagnosed and undertreated in the United States (US), despite guidelines recommendations for universal pediatric lipid screening in children aged 9-11. Early diagnosis and adequate treatment are critical in averting premature cardiovascular disease in individuals affected by HoFH. Yet, an unacceptably high number of people living with HoFH remain undiagnosed, misdiagnosed, and/or receive a late diagnosis, often after a major cardiovascular event. The emergence of novel lipid-lowering therapies, along with the realization that diagnosis is too often delayed, have highlighted an urgency to implement policies that ensure timely detection of HoFH in the US. Evidence from around the world suggests that a combination of universal pediatric screening and cascade screening strategies constitutes an effective approach to identifying heterozygous familial hypercholesterolemia (HeFH). Nevertheless, HoFH and its complications manifest much earlier in life compared to HeFH. To date, little focus has been placed on the detection of HoFH in very young children and/or infants. The 2023 Updated European Atherosclerosis Society Consensus Statement on HoFH has recommended, for the first time, broadening pediatric guidelines to include lipid screening of newborn infants. Some unique aspects of HoFH need to be considered before implementing newborn screening. As such, insights from pilot studies conducted in Europe may provide some preliminary guidance. Our paper proposes a set of actionable measures that states can implement to reduce the burden of HoFH. It also outlines key research and policy gaps that need to be addressed in order to pave the way for universal newborn screening of HoFH in the US.

Nicotine and Cardiovascular Health: When Poison is Addictive - a WHF Policy Brief.

Nicotine is universally recognized as the primary addictive substance fuelling the continued use of tobacco products, which are responsible for over 8 million deaths annually. In recent years, the popularity of newer recreational nicotine products has surged drastically in many countries, raising health and safety concerns. For decades, the tobacco industry has promoted the myth that nicotine is as harmless as caffeine. Nonetheless, evidence shows that nicotine is far from innocuous, even on its own. In fact, numerous studies have demonstrated that nicotine can harm multiple organs, including the respiratory and cardiovascular systems. Tobacco and recreational nicotine products are commercialized in various types and forms, delivering varying levels of nicotine along with other toxic compounds. These products deliver nicotine in profiles that can initiate and perpetuate addiction, especially in young populations. Notably, some electronic nicotine delivery systems (ENDS) and heated tobacco products (HTP) can deliver concentrations of nicotine that are comparable to those of traditional cigarettes. Despite being regularly advertised as such, ENDS and HTP have demonstrated limited effectiveness as tobacco cessation aids in real-world settings. Furthermore, ENDS have also been associated with an increased risk of cardiovascular disease. In contrast, nicotine replacement therapies (NRT) are proven to be safe and effective medications for tobacco cessation. NRTs are designed to release nicotine in a slow and controlled manner, thereby minimizing the potential for abuse. Moreover, the long-term safety of NRTs has been extensively studied and documented. The vast majority of tobacco and nicotine products available in the market currently contain nicotine derived from tobacco leaves. However, advancements in the chemical synthesis of nicotine have introduced an economically viable alternative source. The tobacco industry has been exploiting synthetic nicotine to circumvent existing tobacco control laws and regulations. The emergence of newer tobacco and recreational nicotine products, along with synthetic nicotine, pose a tangible threat to established tobacco control policies. Nicotine regulations need to be responsive to address these evolving challenges. As such, governments should regulate all tobacco and non-medical nicotine products through a global, comprehensive, and consistent approach in order to safeguard tobacco control progress in past decades.

The Impact of Alcohol Consumption on Cardiovascular Health: Myths and Measures.

Over the past several decades, the prevalence of cardiovascular disease (CVD) has nearly doubled, and alcohol has played a major role in the incidence of much of it. Alcohol has also been attributed in deaths due to infectious diseases, intentional and unintentional injuries, digestive diseases, and several other non-communicable diseases, including cancer. The economic costs of alcohol-associated health outcomes are significant at the individual as well as the country level. Risks due to alcohol consumption increase for most cardiovascular diseases, including hypertensive heart disease, cardiomyopathy, atrial fibrillation and flutter, and stroke. The widespread message for over 30 years has been to promote the myth that alcohol prolongs life, chiefly by reducing the risk of coronary heart disease (CHD). Lack of universal advice and stringent policy measures have contributed towards increased uptake and easy availability of alcohol. The WHO has called for a 10% relative reduction in the harmful use of alcohol between 2013-2025. However, lack of investment in proven alcohol control strategies, as well as persistence of misinformation and industry interference, have hindered the efforts of public health professionals to make sufficient progress in reducing alcohol related harms and death.

E-Cigarettes: A New Threat to Cardiovascular Health - A World Heart Federation Policy Brief.

Tobacco is widely recognized as a leading cause of cardiovascular morbidity and mortality, accounting for approximately seventeen percent of all cardiovascular disease deaths globally. Electronic nicotine delivery systems such as e-cigarettes have been developed and advertised as safer alternatives to traditional tobacco cigarettes. Aggressive marketing strategies, as well as misleading claims by manufacturers, have largely contributed to the belief that e-cigarettes are harmless. In reality, e-cigarettes are far from innocuous. E-cigarette solutions and aerosols generally contain harmful substances that are commonly found in tobacco cigarette emissions. A growing body of literature suggests that e-cigarettes are associated with an increased risk of cardiovascular morbidity and mortality. In addition, the effectiveness of e-cigarettes as smoking cessation tools has yet to be determined. Concerningly, most smokers do not give up on tobacco cigarettes and eventually become dual users. Unregulated, e-cigarettes constitute a serious threat to established tobacco control policies. Fortunately, many countries have demonstrated that strong regulations were effective in protecting their populations from the dangers of e-cigarettes. The World Heart Federation recommends applying the precautionary principle and a set of measures to protect vulnerable populations, prevent exposure to second-hand smoking, and address misleading claims. In this regard, we recommend that governments, policymakers, and other relevant stakeholders enact or support the following measures, among others: Prohibit the sale and distribution of e-cigarettes to minors, as well as the use of flavouring agents.Prohibit the use of e-cigarettes anywhere tobacco cigarettes have been banned.Prohibit marketing, advertising, and misleading claims regarding e-cigarettes.Apply excise taxes on e-cigarettes.Conduct more research regarding the long-term effects of e-cigarettes on cardiovascular health. Lastly, countries that have banned the commercialization of e-cigarettes should maintain these measures.

CutA divalent cation tolerance homolog (Escherichia coli) (CUTA) regulates ß-cleavage of ß-amyloid precursor protein (APP) through interacting with ß-site APP cleaving protein 1 (BACE1).

Accumulation of the neurotoxic ß-amyloid (Aß) peptide in the brain is central to the pathogenesis of Alzheimer disease. Aß is derived from the ß-amyloid precursor protein (APP) through sequential cleavages by ß- and γ-secretases, and the production of Aß is greatly affected by the subcellular localization of these factors. CUTA, the mammalian CutA divalent cation tolerance homolog (E. coli), has been proposed to mediate acetylcholinesterase activity and copper homeostasis, which are important in Alzheimer disease pathology. However, the exact function of CUTA remains largely unclear. Here we show that human CUTA has several variants that differ in their N-terminal length and are separated as heavy (H) and light (L) components. The H component has the longest N terminus and is membrane-associated, whereas the L component is N-terminally truncated at various sites and localized in the cytosol. Importantly, we demonstrate that the H component of CUTA interacts through its N terminus with the transmembrane domain of ß-site APP cleaving enzyme 1 (BACE1), the putative ß-secretase, mainly in the Golgi/trans-Golgi network. Overexpression and RNA interference knockdown of CUTA can reduce and increase BACE1-mediated APP processing/Aß secretion, respectively. RNA interference of CUTA decelerates intracellular trafficking of BACE1 from the Golgi/trans-Golgi network to the cell surface and reduces the steady-state level of cell surface BACE1. Our results identify the H component of CUTA as a novel BACE1-interacting protein that mediates the intracellular trafficking of BACE1 and the processing of APP to Aß.