Transcript
Blood Lipids & Cardiovascular Disease
Milly Ryan-Harshman, PhD, RD
Atherogenic Dyslipidemia
Atherogenic dyslipidemia is any abnormal pattern of blood lipid profile that promotes the development of atherosclerosis.
Atherogenic dyslipidemia is a feature of several metabolic conditions which increase risk for coronary artery disease including overweight/obesity, insulin resistance and the metabolic syndrome, and type 2 diabetes.
Atherogenic Dyslipidemia
High triglycerides, low HDL cholesterol levels and an increase in the number of small, dense LDL particles are characteristics of atherogenic dyslipidemia.
This phenotype is influenced by both genetic and environmental factors.
Atherosclerosis
Atherosclerosis
Major LDL Subclasses
LDL actually represents a heterogeneous population of particles that can be differentiated according to particle density, size, charge, and chemical composition.
It is the small, dense LDL that have been associated with coronary heart disease risk (LDL3 and LDL4).
Major LDL Subclasses
Plasma triglyceride and very low density lipoprotein (VLDL) levels have been strongly associated with decreasing size and increasing density of LDL particles.
Insulin resistance is closely tied to the “pattern B” phenotype for atherogenic dyslipidemia – high triglycerides, low HDL, smaller LDL. However, many overweight people can have the “pattern B” phenotype, but not be defined as having the metabolic syndrome.
Major LDL Subclasses
“Pattern B” patients have been shown to have an increased risk for hypertension.
Both type 1 and type 2 diabetics may have increases in LDL3 and LDL4.
“Pattern A” individuals – large, buoyant LDL particles (low risk)
“Pattern B” individuals – small, dense LDL particles (high risk)
“Pattern B” Genetic Studies
Numerous studies have been conducted and are being undertaken to determine the actual genetic effects on lipoprotein characteristics.
However, the heritability of LDL particle size, as demonstrated in twin studies, is relatively low, suggesting that non-genetic and environmental influences on the expression of the “pattern B” phenotype are significant.
Dietary Effects on LDL Subclasses: “Pattern A”
Dietary Effects on LDL Subclasses: “Pattern B”
Dietary Effects on LDL Subclasses
Both “pattern A” and “pattern B” patients responded to low-fat diets with reductions in LDL-C, but the mechanisms were different.
When switched to the high-fat diet, “pattern B” patients exhibited a twofold greater reduction in LDL cholesterol compared to “pattern A” patients.
A significant number (41%) of persons who were “pattern A” on the high-fat diet converted to the “pattern B” phenotype on the low-fat, high carbohydrate diet.
Dietary Effects on LDL Subclasses
Substituting carbohydrate for fat increases the number of people, especially men, who convert from the “pattern A” phenotype to the “pattern B” phenotype.
Basically, the appropriate diet is to substitute carbohydrate with protein, keeping fat intake the same (the Syndrome X diet!).
Why? High carbohydrate raises triglycerides, and triglycerides have been associated with decreasing size and increasing density of LDL particles as stated earlier.
Characteristics of main types of hyperlipoproteinemias
Genetic polymorphisms, blood lipid levels, and dietary intervention
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Chol
Chol
Low-fat, high carbohydrate
Larger LDL
Smaller LDL
Apo B
=
Apo B
Less cholesterol per particle, but a similar number
of particles, i.e., same Apo B (major structural protein).
Chol
Chol
Chol
Chol
Chol
Chol
Chol
Low-fat, high carbohydrate
Reduced number of particles, i.e.,
less Apo B.
Weight reduction, low fat diet, no alcohol
Risk of atherosclerosis is not clear
Very greatly increased
Normal or slightly increased
VLDL increased, chylomicrons increased, HDL decreased
V
Weight reduction, low carbohydrate diet, no alcohol
Possible risk, especially for coronary atherosclerosis
Greatly increased
Normal or slightly increased
VLDL increased, HDL decreased?
IV
Weight reduction, maintain low cholesterol balanced diet
Very strong risk, especially in peripheral and coronary arteries
Greatly increased
Greatly increased
IDL greatly increased
III
Low cholesterol, low-fat diet
Very strong risk of coronary atherosclerosis
Normal in type IIa, slightly increased in type IIb
Greatly increased
LDL greatly increased
II
Low fat diet, no alcohol
No increased risk of atherosclerosis
Very greatly increased
Normal or slightly increased
Chylomicrons greatly increased; HDL decreased
I
Dietary Treatment
Risk
Triglycerides
Total cholesterol (TC)
Lipoproteins Affected
Type
High intakes of saturated fat and cholesterol yield greater than expected serum cholesterol increases; greater LDL-C reductions when consuming low-fat, low cholesterol diet
High
Highest
Highest
ApoE4 allele at the APOE gene
Tendency toward cholesterol raising effect of high saturated fat intake
Inter-
mediate
Intermediate
ApoE3 allele at the APOE gene
Ability to lower serum cholesterol enhanced by higher intakes of saturated fat & cholesterol; high intakes of sucrose associated with high serum TGs
High
Low
Low
ApoE2 allele at the APOE gene
Dietary effects
Effect on TG
Effect on LDL-C
Effect on HDL-C
Effect on TC
Polymorphism
Increased HDL-C levels in response to higher dietary fat content
CC genotype (most common among Caucasians) at the hepatic lipase gene
GG allele in women had higher HDL-C concentrations when PUFAs were <4% of total energy, but women with the GA allele had higher HDL-C concentrations only when PUFAs were >8% of total energy
As intake of PUFAs increases, HDL-C levels decrease
G allele at the APOA1 gene (More common)
Individuals with low HDL-C levels and this allele might benefit from higher intakes of PUFAs
Increased concentration with increased intakes of PUFAs
A allele at the APOA1 gene
A low-fat, high carbohydrate diet tends to convert to LDL sub-type that increases risk of IHD
Large, buoyant LDL particle sub-type
Phenotype A (both phenotypes appear to be inherited as a single gene trait)
Low fat diet appropriate to reduce risk of ischemic heart disease (IHD)
High
Small, dense LDL particle sub-type
Low
Increased mass of VLDL/IDL
Phenotype B (increased apolipoprotein B, the major protein component of LDL; decreased apolipo-protein A-I, the major component of HDL
Higher HDL levels among moderate drinkers
ADH3 allele (slower alcohol metabolism)
Highest HDL-C concentrations achieved when total fat intake was <30% of energy and low in animal fat (Mediterranean diet)
Higher dietary fat content decreases HDL-C levels
TT genotype at the hepatic lipase gene
