Summary of Study Results
linking PCBs and Coronary Artery Disease
Each entry below represents a finding in a study --- some studies had multiple findings. For more information, see Heart Table of Contents) Keep in mind that not all studies are equal in size or quality. Some examine the effects of old PCB commercial mixtures (which had variable composition), or just one or two individual types of PCBs (out of 209 possible.)
- PCBs have been implicated in the atherosclerotic process (coronary artery disease)
- PCBs may cause atherosclerotic disease through one or more of these mechanisms:
- alteration in lipid profile and lipid metabolism
- cytochrome P-450 1A1 induction
- increased oxidative stress
- DNA adduct formation and oxidative DNA damage
- alteration of calcium metabolism
- PCBs cause endothelial cell dysfunction, which is a trigger for cardiovascular disease
- Vitamin E and other antioxidants may limit endothelial cell injury by PCBs
- PCBs may play a role in atherosclerosis by causing endothelial cell dysfunction and a decrease in the barrier function of the vascular endothelium (5 studies)
- linoleic acid [from a high-fat diet] can amplify PCB-induced endothelial cell dysfunction -- severe toxicity of PCBs in the presence of linoleic acid may be due in part to the generation of epoxide and diol metabolites
- PCBs cause vascular endothelial cell dysfunction by modulating intracellular glutathione, which subsequently leads to activation of stress-specific kinases
- inhibition of glutathione synthesis by buthionine-sulphoximine can increase the PCB -induced stress response and lead to cell death
- PCBs may act with other chemical contaminants to cause circulatory damage
- significantly increased mortality from cardiovascular diseases (2 studies)
- mortality occurred 20 years after PCB exposure
- PCBs were present at increased levels in heart patients
- PCBs may have long-term cardiovascular consequences (2 studies)
- PCBs are statistically associated with cardiovascular disease risk factors
- PCBs are considered a protoxicant in the circulatory system, possibly through effects on cytochrome P450 and enzymes
- disruption of cell-growth, differentiation or apoptosis (cell death) during embryonic or fetal development could lead to cardiovascular dysfunction (heart disease)
- serum cholesterol levels in humans are significantly correlated with PCB levels (15 studies)
- PCB distribution between different lipoproteins was very similar to distribution of cholesterol
- plasma triglyceride level showed a significantly positive correlation with blood PCB level (18 studies)
- elevated blood-serum triglycerides were frequent symptoms in 1,081 people poisoned with PCBs
- clear positive association between blood PCB and serum triglyceride in patients 20 years after PCB exposure
- lipoprotein abnormalities are standard clinical signs or symptoms of PCB poisoning
- the most likely PCB biomarkers of effect included some form of alteration in lipid metabolism (serum triglyceride/cholesterol levels)
- PCBs are associated with various serum lipids
- PCBs are known to cause acute and chronic hyperlipidemia
- PCB's are fat soluble and mainly transported by triglycerides with lipoproteins (2 studies)
- highly chlorinated PCBs (Aroclor 1260) had significant, positive correlations with several serum analytes
- less chlorinated PCBs (Aroclor 1242) correlated significantly and negatively only with HDL-cholesterol (ie: PCBs reduced the good cholesterol)
- PCBs inversely correlated with plasma high density lipoprotein (HDL) cholesterol (ie: PCBs reduced the good cholesterol)
- low density lipoproteins (LDL), bad cholestorol, correlates with PCB levels (ie: PCBs increase the bad cholesterol)
- lipoproteins take part in the uptake and egress of PCBs from skin fibroblasts
- PCB binding to lipoproteins has important biological implications
- PCB exhibits a homogeneous distribution among lipoproteins and the heaviest fraction.
- 70 to 75 percent of PCBs partition into plasma and 25 to 30 percent to the erythrocytes
- methylsulfonyl metabolites of PCBs were distributed equally among the LDL and HDL fractions
- PCB 153 is used as a model of lipophilic (fat-loving) compounds which are unmetabolizable
- induction of liver enzymes have been consistently observed (2 studies)
- increased liver enzyme gamma-glutamyl transpeptidase (GGTP) (4 studies)
- increased liver enzyme serum glutamic-oxaloacetic transaminase (SGOT) (3 studies)
- serum PCB levels were positively and significantly correlated with total bilirubin (2 studies), conjugated bilirubin, beta-glucuronidase (2 studies), 5'-nucleotidase (2 studies), serum apolipoprotein-Al, serum apolipoprotein-B, urinary creatinine, and urinary alanine-aminopeptidase
- fat levels of PCBs correlate with urinary 17-hydroxycorticosteroid excretion
- PCBs are taken into human plasma albumin and albumin levels correlate with PCB levels
- PCB binding to albumin has important biological implications
- synthesis of phospholipids increased dramatically due to PCBs
- certain PCBs cause a significant change in bilayer fluidity in phospholipid bilayers in the presence and absence of cholesterol, other PCBs do not have this effect
- PCB toxicity may be related to its capacity to alter phosphoglyceride metabolism
- PCBs interact with acetate to cause enhanced effects
- PCBs concentrate in brown fat
- different laboratories reported significantly different serum lipid PCB levels from the same sample
- improved analytical methods are needed
- PCBs are correlated with beef, lamb, and fish consumption
- positive association between fish consumption and PCB concentrations among women in the Northeast and Midwest
- the most important predictors of PCBs were age, serum cholesterol, and residence in the Midwest or Northeast
- therapy achieved significant reductions in total cholesterol levels
- PCB excretion from the body is influenced by increases or declines in fat storage
- high blood pressure has a dose-response relationship with serum PCB levels
- six groups of investigators have found associations between PCB or chlorinated pesticide levels and blood pressure
- PCBs were weakly correlated with systolic blood pressure and liver enzyme activities, at background levels
- PCB levels were positively associated with gamma-glutamyl transpeptidase level, serum cholesterol level, and measured blood pressure
- 100 percent of the dioxin was associated with plasma and none with red blood cells (some PCBs are dioxin-like)
- in plasma, 84 to 89 percent of dioxin could be recovered from lipoprotein fractions
- dioxins cause early atherosclerosis and reduction in the contraction force of the heart atrial muscles (certain PCBs are dioxin-like)
Summary of Studies with Negative Results
(Note: Some of these were studies too small to establish statistical significance, or occupational studies with uncertain amounts and types of PCB exposures. A few studied the same populations which were studied above several times with conflicting results.) Some studies were funded by corporations with a financial interest in showing negative results.
- no relationship found between PCBs and cholesterol, hematocrit or blood pressure
- no significant correlation found between PCB levels and cholesterol or high-density lipoprotein
- no differences in fasting serum triglycerides, total cholesterol, low density lipoproteins, high density lipoproteins, or very low density lipoproteins.
- no correlation found between blood PCB and triglycerides, total cholesterol, or beta lipoprotein.
- no significant associations between lipid PCB levels and clinical indicators of hepatotoxicity, hypertension, or pulmonary impairment
- serum triglyceride concentrations showed no consistent relation to PCB concentrations (small study)
- blood pressure was not associated with blood PCB levels and PCB patterns
- cholesterol and hepatic functions were normal
- the collective occupational experience with PCB fluids provides no evidence for adverse PCB effects other than dermal effects
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