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"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

The epidemiology of hypercholesterolemia has been shifting in recent years.

The optimal total cholesterol level is defined as about 150 mg/dL, putting low-density lipoprotein (LDL) cholesterol level at 100 mg/dL and high-density lipoprotein (HDL) around at least 40 mg/dL for men and 50 mg/dL for women.

High total cholesterol is defined by a non-HDL level of 240 mg/dL or greater. Hypercholesterolemia is diagnosed when non-HDL levels rise above 130 mg/dL.

"If the entire population maintained LDL concentrations akin to those of a neonate (or to those of adults of most other animal species), atherosclerosis might well be an orphan disease," notes a .

While that is nowhere near the case, hypercholesterolemia as a contributor has shown improvement in recent years as measured in U.S. population-level prevalence in the U.S. National Health and Nutrition Examination Survey (NHANES).

Falling Prevalence

The in U.S. youth declined from 9.2% in 2007-2010 to 6.4% in 2013-2016. For U.S. adults age 20 and older, the prevalence of high total cholesterol declined from 18.3% in 1999-2000 to 10.5% in 2017-2018. However, a recent showed elevated non-HDL cholesterol in 20.7% of those with total cholesterol under 190 mg/dL while not on lipid-lowering therapy.

Among U.S. adults in 2017-2020 , elevated LDL levels are equally common in females and males, although women have a higher prevalence of total cholesterol over 200 mg/dL (36.2% vs 32.8% of males).

Familial hypercholesterolemia, one of the most common genetic diseases, affects 1 in 250 individuals as a heterozygous condition and 1 in 300,000 in its more severe homozygous form. Certain populations, such as those with French Canadian, Lebanese, and , can have a prevalence as high as 1 in 100.

Diverging Trends

While hypercholesterolemia and consequent atherosclerosis might be improving in the United States, the trend is not so rosy for much of the rest of the non-Western world.

"Although atherosclerotic cardiovascular disease was previously considered a problem that was concentrated in the industrialized world, it now spans the globe. We have witnessed an 'epidemiological transition,'" that has seen atherosclerosis now involved in the majority of deaths worldwide, as the Nature review points out. "Atherosclerosis now affects younger people, and more women and individuals from a diverse range of ethnic backgrounds, than was formerly the case."

Another showed a constant reduction in non-HDL cholesterol in the last four decades in high-income countries, "especially starting from 1990, likely due to an increase in the use of statins." By contrast, low-income and lower middle-income groups showed rising levels of non-HDL cholesterol across those years, both in men and women.

U.S. trends for improvement have likewise been similar for men and women, and only Asian adults have been left out of significant reductions in total cholesterol, according to of the NHANES data for 2007-2018.

Risk factors for high cholesterol include:

• Obesity

• Diet high in saturated or trans fats

• Lack of exercise

• Age older than 40

• Asian Indian, Filipino, or Vietnamese ancestry

• Female gender at birth

• Postmenopausal status

• Smoking

• Family history of premature atherosclerotic cardiovascular disease (<55 years if male or <65 if female)

Interconnected Conditions

Comorbidities of high cholesterol include obesity, diabetes mellitus, hypertension, and heart disease. It can also coexist with arthritis, sleep apnea, and atrial fibrillation. Interestingly, high cholesterol is associated with better outcomes in heart failure (HF), although a from the American Heart Association notes that it's not clear "whether low cholesterol levels play a causative role in the worse outcome of patients with HF or whether low cholesterol levels merely reflect an advanced disease state."

Familial hypercholesterolemia patients have a higher prevalence of chronic kidney disease, but results are inconsistent about the prevalence of comorbid hypertension and whether diabetes is more common in these patients or not, a concluded.

The Atherosclerosis Risk in Communities (ARIC) study showed the declining influence of hypercholesterolemia as a contributor to cardiovascular disease risk. While a major contributor to risk in the late 1980s, with a population-attributable risk of 18%, there was a trend for decline in that impact. By 1996-1998, the population-attributable risk was just 9%, due in part to lower prevalence and potentially better treatment.

Another study estimated that 13% of cardiovascular disease in the United States in 2007-2015 was to high cholesterol, compared with 6.9% in Iran and 20% in Spain.

Worldwide, LDL cholesterol was the third highest contributor to years of disability-adjusted life years related to cardiovascular disease in 2019, after high systolic blood pressure and dietary risks, according to the .

The biggest causal role is in ischemic heart disease, with 44% of global deaths from that cause attributable to high LDL cholesterol, according to one . A found a population-attributable fraction of cardiovascular disease, coronary heart disease, and cardiac deaths due to hypercholesterolemia of 1.7%, 10.6%, and 5.6%, respectively. A also estimated that 8.2% of all deaths in Austria are attributable to hypercholesterolemia.

However, "there is no significant direct relation between an increased risk of stroke and increased plasma total cholesterol or low density lipoprotein cholesterol," noted a review in . "Indeed, an inverse relation exists between total cholesterol concentrations and cerebral hemorrhage."

Read previous installments in this series:

Part 1: Hypercholesterolemia: A Complex System

Part 2: Consequences of Hypercholesterolemia

Part 3: Genetics of Hypercholesterolemia

Part 4: Case Study: High Lipoprotein(a) Levels in Younger Patients Are Not So Clear Cut

Up next: Diagnosing Hypercholesterolemia