The big picture: LDL cholesterol is a substance that can accumulate in your arteries, leading to a buildup that eventually obstructs blood flow. Your risk of heart attack and stroke rapidly multiplies the longer you have high levels of LDL cholesterol in your bloodstream. Therefore, early and sustained reduction of LDL cholesterol is crucial to minimize these risks.

Cholesterol is not bad: LDL cholesterol is often called the "bad cholesterol” but this can be misleading. Cholesterol itself is a crucial, uniform substance necessary for life. For example, it plays an essential role in building cell membranes, hormones and vitamins. However, the way cholesterol is transported in the blood is not uniform and this is what can lead to health problems.

But LDL is bad: Cholesterol is moved around the body by particles called lipoproteins, and LDL is one such particle. Among other functions, LDLs carry and deposit cholesterol and other substances into the arteries. This action can result in the buildup of plaque within the arteries, known as atherosclerosis, a major contributor to cardiovascular issues.

LDL and heart health: Over time, the plaques formed by LDL cholesterol can thicken and harden, narrowing the arteries and restricting the flow of oxygen-rich blood. This obstruction can result in serious health conditions, including heart attacks and strokes. Research consistently shows direct correlation between lowering LDL cholesterol correlates and decreased risk of cardiovascular diseases.

A meta-analysis of 14 trials (n=90,056) observed that a 38.7-mg/dL (1-mmol/L) reduction of LDL cholesterol levels is accompanied by a 21% reduction in the risk of cardiovascular disease.
As a rough guide, a lowering of LDL cholesterol levels of 1% gives an approximate 1% reduction in the risk of cardiovascular disease – somewhat more at higher baseline LDL cholesterol levels and somewhat less at lower baseline levels.

Cumulative exposure matters most: The impact of LDL cholesterol is cumulative, similar to the risks of long-term smoking or high blood pressure on cardiovascular health. The longer you have high levels of LDL cholesterol, the greater your risk of cardiovascular issues. Cumulative exposure is measured in mg-years (Age x LDL cholesterol in mg/dL). For instance, a 40-year-old with a lifelong LDL cholesterol level of 150 mg/dL would have an exposure of 6000 mg-years.

Cumulative LDL exposure mg-years	% risk of heart attack
5000	1%
6250	2%
7500	8%
10000	16%
11250	32%
12500	64%

The lower the sooner the better: The risk of heart attack increases significantly once cumulative LDL exposure reaches certain thresholds, e.g. already 1% at just 5000 mg-years. Notably, reducing LDL cholesterol as much as possible offers no drawbacks, only benefits.

Start lowering your LDL cholesterol now: Starting early to reduce your LDL cholesterol can substantially decrease the risk of heart disease as one ages. For example, a 40-year-old with a steady LDL level of 150 mg/dL faces around a 60% heart attack risk by age 80. If he reduced today to 80 mg/dL, this risk drops to about 10% at the same age, highlighting the importance of early and sustained LDL cholesterol management.

Direct vs. calculated LDL cholesterol: In clinical practice, LDL cholesterol levels are either calculated, typically using the Friedewald formula, or measured directly. The calculated method, while convenient and cost-effective, may lose accuracy in cases of high triglycerides or certain metabolic conditions. Direct measurement, though more precise and essential in certain clinical scenarios (like severe hypertriglyceridemia or diabetes), is less commonly used due to its higher cost and is usually reserved for more specialized assessments.