September 16, 2008JAMA83 citations
The Multiple Risk Factor Intervention Trial (MRFIT)—Importance Then and Now
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Key Result
Serum cholesterol levels showed a continuous, graded relationship with coronary heart disease death, with a relative risk of 3.42 for the highest versus lowest quintile.
Key Points
- The study aims to examine the long-term relationship between serum cholesterol levels and coronary heart disease (CHD) related deaths among middle-aged men.
- Analyzed a cohort of 356,222 men aged 35 to 57 years free from previous heart attack history.
- Calculated age-adjusted risks of CHD death based on standardized serum cholesterol measurements across quintiles.
- Included diverse subgroups, such as hypertensive and nonhypertensive individuals, as well as smokers and nonsmokers.
- Mortality risk for CHD death increased continuously across cholesterol quintiles with relative risks of 1.29, 1.73, 2.21, and 3.42 for quintiles 2 to 5 compared to the lowest quintile.
- 46% of CHD deaths were excess deaths tied to serum cholesterol levels ≥180 mg/dL, with significant contributions from cholesterol quintiles 2 to 4.
- Strong graded relationship between serum cholesterol and six-year age-adjusted CHD death rate was consistent across various demographic groups.
Study Design
Type
Cohort (n=356,222)
Structured PICO
Is there a continuous and graded relationship between serum cholesterol levels and coronary heart disease death in middle-aged men?
P
Population
356,222 American men aged 35 to 57 years, free of prior hospitalization for myocardial infarction, followed for 6 years to assess the relationship between serum cholesterol and CHD death.
C
Comparator
Lowest quintile of serum cholesterol (<182 mg/dL)
O
Outcome
Coronary heart disease (CHD) death ratehard clinical
This foundational cohort study demonstrated that the relationship between serum cholesterol and CHD death is continuous, graded, and strong, without a threshold effect, affecting the vast majority of middle-aged men.
Main Result
Relative Risk: 3.42
Abstract
The 356 222 men aged 35 to 57 years, who were free of a history of hospitalization for myocardial infarction, screened by the Multiple Risk Factor Intervention Trial (MRFIT) in its recruitment effort, constitute the largest cohort with standardized serum cholesterol measurements and long-term mortality follow-up. For each five-year age group, the relationship between serum cholesterol and coronary heart disease (CHD) death rate was continuous, graded, and strong. For the entire group aged 35 to 57 years at entry, the age-adjusted risks of CHD death in cholesterol quintiles 2 through 5 (182 to 202, 203 to 220, 221 to 244, and ≥245 mg/dL 4.71 to 5.22, 5.25 to 5.69, 5.72 to 6.31, and ≥6.34 mmol/L) relative to the lowest quintile were 1.29, 1.73, 2.21, and 3.42. Of all CHD deaths, 46% were estimated to be excess deaths attributable to serum cholesterol levels 180 mg/dL or greater (≥4.65 mmol/L), with almost half the excess deaths in serum cholesterol quintiles 2 through 4. The pattern of a continuous, graded, strong relationship between serum cholesterol and six-year age-adjusted CHD death rate prevailed for nonhypertensive nonsmokers, nonhypertensive smokers, hypertensive nonsmokers, and hypertensive smokers. These data of high precision show that the relationship between serum cholesterol and CHD is not a threshold one, with increased risk confined to the two highest quintiles, but rather is a continuously graded one that powerfully affects risk for the great majority of middle-aged American men.See PDF for full text of the original JAMA article.
Cite This Study
Jeremiah Stamler (2008) conducted a cohort in Coronary heart disease (n=356,222). Serum cholesterol vs. Lowest quintile of serum cholesterol was evaluated on Coronary heart disease (CHD) death (RR 3.42). Serum cholesterol levels showed a continuous, graded relationship with coronary heart disease death, with a relative risk of 3.42 for the highest versus lowest quintile.