Friday, March 15, 2013

Relationship Between Serum Cholesterol And Heart Disease

I've been reviewing the literature for the relationship between serum cholesterol and coronary heart disease (CHD). Below are some studies. I'll add to this post as I find more. All of these studies show that having a total cholesterol above 200 mg/dl (perhaps above 180 mg/dl) or an LDL cholesterol above 100 mg/dl (perhaps above 70 mg/dl) significantly increases the risk for heart disease.

Is Relationship Between Serum Cholesterol And Risk Of Premature Death From Coronary Heart Disease Continuous And Graded?, JAMA 1986
"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."

Serum Cholesterol Concentration And Coronary Heart Disease In Population With Low Cholesterol Concentrations, BMJ 1991
"DESIGN--Prospective observational study based on 8-13 years of follow up of subjects in a population with low cholesterol concentrations. SETTING--Urban Shanghai, China. SUBJECTS--9021 Chinese men and women aged 35-64 at baseline.
There was a strongly positive, and apparently independent, relation between serum cholesterol concentration and death from coronary heart disease (z = 3.47, p less than 0.001), and within the range of usual serum cholesterol concentration studied (3.8-4.7 mmol/l) [148-183 mg/dl] there was no evidence of any threshold."

Relationship Of Baseline Serum Cholesterol Levels In 3 Large Cohorts Of Younger Men To Long-term Coronary, Cardiovascular, And All-Cause Mortality And To Longevity, JAMA 2000

The 3 cohorts were:
  • 11,017 men aged 18-39 years: Chicago Heart Association Detection Project in Industry (CHA), 25 years follow-up
  • 1266 men aged 25-39 years: Peoples Gas Company Study (PG), 34 years follow-up
  • 69,205 men aged 35-39 years: Multiple Risk Factor Intervention Trial (MRFIT), 16 years follow-up
"Men in all 3 cohorts with unfavorable serum cholesterol levels (200-239 mg/dL and ≥240 mg/dL) had strong gradients of relative mortality risk."
"These results demonstrate a continuous, graded relationship of serum cholesterol level to long-term risk of CHD, CVD, and all-cause mortality, substantial absolute risk and absolute excess risk of CHD and CVD death for younger men with elevated serum cholesterol levels, and longer estimated life expectancy for younger men with favorable serum cholesterol levels."
"Improved nutrition to reduce serum cholesterol levels is efficacious for the whole population, including all young adults and particularly those who already have unfavorable levels."

Serum Cholesterol, Haemorrhagic Stroke, Ischaemic Stroke, And Myocardial Infarction: Korean National Health System Prospective Cohort Study, British Medical Journal, 2006
"Ischaemic stroke and myocardial infarction were strongly and positively associated with blood cholesterol."
In this study of 787,442 men and women, a serum cholesterol of 200-240 mg/dl increased the risk for a heart attack by two and a half times (compared to a cholesterol of 130 mg/dl), a cholesterol of 240-270 mg/dl increased the risk almost 4 times, over 270 mg/dl increased the risk by 6.25 times! Those figures were adjusted for age and sex.


Blood Cholesterol And Vascular Mortality By Age, Sex, And Blood Pressure: A Meta-analysis Of Individual Data From 61 Prospective Studies With 55,000 Vascular Deaths, Lancet, 2007
"1 mmol/L [about 39 mg/dl] lower total cholesterol was associated with about a half, a third, and a sixth lower IHD [ischaemic heart disease] mortality in both sexes at ages 40—49, 50—69, and 70—89 years, respectively, throughout the main range of cholesterol in most developed countries, with no apparent threshold.
Total cholesterol was positively associated with IHD mortality in both middle and old age and at all blood pressure levels."

Non-Optimal Lipids Commonly Present In Young Adults And Coronary Calcium Later In Life, The Coronary Artery Risk Development In Young Adults (CARDIA) Study, Annals of Internal Medicine, 2010
For "black and white men and women recruited at age 18-30 ... non-optimal LDL [>100 mg/dl] and HDL [<60 mg/dl] cholesterol at commonly observed levels during young adulthood are independently associated with coronary atherosclerosis two decades later.

From the studies above, having a total cholesterol above 200 mg/dl (perhaps above 180 mg/dl) or an LDL cholesterol above 100 mg/dl (perhaps above 70 mg/dl) increased the risk for coronary heart disease. This relationship was graded, so the higher the serum cholesterol, the greater the CHD risk. "No threshold level" means there was no level below which cholesterol was not associated with lower risk. When it came to heart disease, the lower the cholesterol, the better.


Healthy Longevity said...

Here are some more papers.

Meta-analysis of 108 randomized controlled trials:
"Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis"

Meta-analysis of mendelian randomization studies:
"Effect of Long-Term Exposure to Lower Low-Density Lipoprotein Cholesterol Beginning Early in Life on the Risk of Coronary Heart Disease A Mendelian Randomization Analysis"

Large Prospective Cohort Studies:

"Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths"

"Major Lipids, Apolipoproteins, and Risk of Vascular Disease"

"Serum cholesterol, haemorrhagic stroke, ischaemic stroke, and myocardial infarction: Korean national health system prospective cohort study"

"Joint Effects of Systolic Blood Pressure and Serum Cholesterol on Cardiovascular Disease in the Asia Pacific Region"

Bix said...

Oh, I'm so glad you stopped by. I'll have a look at these.

The NHLBI is coming out with a new set of guidelines for cholesterol, maybe in the next few months:

This Nature article suggests they may "relax" targets:

Cholesterol limits lose their lustre: Revised guidelines for heart health are set to move away from target-based approach.

Should be interesting.

Bix said...

The thing is ... arguing for lower serum cholesterol in this country argues for drug use.

So, drug companies won't be happy if government relaxes targets.

But serum cholesterol (total, LDL, etc.) is only a marker. Lowering a marker by taking a drug does not necessarily lower risk for heart attack, stroke.

Bix said...

Low-carb diets increase cholesterol:

25-Year Study Finds Low-Carb Diets Increase Cholesterol