_______________________________________ Hyperlipidemias and Atherosclerotic Cardiovascular Disease
In the United States in 2014–2015, the estimated direct and indirect cost of ASCVD was $351.2 billion [1]. This figure is projected to increase to $1.1 trillion by 2035 [1]. As a comparison, the estimated 2011 annual direct cost of all cancer and benign neoplasms combined is $84 billion, versus $213.8 billion for direct costs of ASCVD [1]. The elevated costs of cardiovascular pathology for individuals, society, and healthcare systems require a novel approach based not only on improved diagnosis and management of disease but primarily on more effective prevention and early intervention. This not only requires a change in general perceptions but also a different approach toward prevention by physicians and other healthcare professionals [9; 10]. The etiology of ASCVD is complex and multifactorial and influenced by a variety of modifiable (e.g., hyperlipidemia, obesity, hypertension, diabetes, smoking, physical inactivity, diet) and non-modifiable (e.g., family history, age, gender) risk factors. Modifiable risk factors play a fundamental role in primary and secondary prevention of ASCVD and account for up to 90% of population-attributable cardiac risk [11; 12]. A high concentration of plasma lipids (i.e., cholesterol and triglycerides), and high concentrations of low-density lipoprotein (LDL) cholesterol in particular, are implicated in the etiology of atherosclerosis and the increased incidence of ASCVD such as coronary artery disease, peripheral vascular disease, and ischemic cerebrovascular disease. Hyperlipidemias are also associated with primary hypertension and metabolic syndrome [13; 14]. The prevalence of hypertriglyceridemia approaches 11% in adolescents 12 to 19 years of age, mostly from secondary causes such as obesity and diabetes. Studies show that atherosclerotic processes are evident in early adolescence, with fatty streaks reported in the aorta and coronary arteries of patients as young as 10 years of age [241]. American Heart Association data from 2015 to 2018 show unfavorable lipid measures of LDL cholesterol >130 mg/dL were present in 27.8% of adults 20 years of age and older, and total blood cholesterol concentrations >240 mg/dL (6.2 mmol/L) were present in 11.5% of adults [234]. Both lipid parameters are associated with excess risk of cardiovascular morbidity and mortality [15]. Hyperlipidemia, and specifically hypertriglyceridemia (150–400 mg/dL or 1.7–4.5 mmol/L), is often present in patients with metabolic syndrome, a disorder characterized by abdominal obesity, hypertension, insulin resistance, low levels of high- density lipoprotein (HDL), and increased risk of ASCVD [13]. Plasma triglyceride concentration is a biomarker for triglyceride rich lipoproteins and their remnants, now recognized as important contributors to ASCVD and pancreatitis [243]. Severe hypertriglyceridemia is the etiologic factor in 7% of pancreatitis cases. Hypertriglyceridemia-induced pancreatitis rarely occurs unless levels exceed 1,700 mg/dL (20 mmol/L) [16].
INTRODUCTION AND EPIDEMIOLOGY OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASES Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in developing countries and accounts for 25.7% of all deaths in the United States and 45% of deaths in Europe [1; 2]. According to the World Health Organization (WHO), 17.9 million people die each year from cardiovascular disease, an estimated 32% of all deaths worldwide [3]. More than four out of five cardiovascular disease deaths are caused by myocardial infarctions and strokes, and one-third of these occur prematurely in persons younger than 70 years of age. It has been estimated that by 2030, ASCVD will account for approximately 23 million annual deaths worldwide, an increase of more than 5 million from current estimates [3]. In the United States, 38% of adults affected by ASCVD have modifiable risk factors such as hyperlipidemia, diabetes, and hypertension [241]. In developed countries, both the prevalence of ASCVD and the rate of mortality have declined. In the United States, from 2006 to 2016, the number of heart-related deaths declined by 18.6%. The prevalence and mortality rates have decreased as the result of risk factor reduction and advances in diagnosis and medical and surgical treatments [1; 4; 5; 6]. Developing countries, however, are continuing to face an increase in ASCVD, which has been attributed to increase in prevalence of hypertension, hyperlipidemia, and diabetes, as well as a 75% increase in tobacco consumption between 1991 and 2001 [7]. Tobacco smoking is among the top three risk factors that account for the most disease burden in China and India [8]. Despite progress in risk factor reduction and a decline in heart-related deaths, most adults in the United States still have elevated long-term risks of cardiovascular disease. In a study published 2025, national survey data between 2011 and 2020 were used to determine the long-term risks of total cardiovascular disease (ASCVD and heart failure) in the United States. The study population consisted of 14,184 adults 30 to 79 years of age, representing 161 million adults with and without cardiovascular disease. The prevalence of existing CVD was 10%, including 27% among adults 65 to 79 years of age. Prevalence of having elevated 10-year risk of developing CVD was 1.0% in adults 30 to 44 years of age, 18% in adults 45 to 64 years, and 66% in adults 65 to 79 years of age. Among adults 30 to 59 years of age, 67% were without CVD but had an elevated 30-year risk of CVD. The author’s summary concluded the following: 3 in 10 U.S. adults have existing CVD or an elevated 10-year predicted risk of CVD; two-thirds of middle-aged adults are without CVD but have an elevated 30-year risk; and men and Black and Hispanic adults are at higher risk. These findings highlight the need for ongoing intensive efforts to prevent ASCVD and all-cause CVD [242].
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