Hyperlipidemia and atherosclerosis.
Know the causes and if you are at risk of Early Onset Heart Disease, FH Disorder, or Inherited High Cholesterol FH is short for Familial Hypercholesterolemia. Cholesterol and Atherosclerosis: The Bad and the Good The link between cholesterol and life threatening events makes treating high. Combined hyperlipidemia, simple hypercholesterolemia, MetS, and low HDL-c However, the relationship between subclinical atherosclerosis and .. produced inconsistent results, meaning that no convincing evidence is.
Mechanisms of hypercholesterolemia and atherosclerosis. Hypercholesterolemia is the result of an imbalance between two basic cholesterol homeostatic mechanisms. One is related to intercellular and the other to extracellular cholesterol homeostasis. The human organism gives always absolute priority to the intracellular homeostasis. The naturally occurring balance between both systems can be disturbed: Total genetic absence of malfunction of LDL-receptors is seen in homozygote familial hypercholesterolemia, with ischemic heart disease between ages 2 and Less harmful situations arise from heterozygote familial hypercholesterolemia and from other genetic defects among them those located at the gene of apo E on chromosome 19 and of apo AI on chromosome This has been demonstrated in the rabbit, hamster, dog, baboon and humans.
Overloading the organism with dietary cholesterol and saturated fat is one extremely common factor in western societies. Certain fats omega-6 and omega-3 polyunsaturated, and oleic acid may be beneficial. As expected, the majority of the normolipidemia group had no CAC-affected vessels.
In comparison, all dyslipidemia groups except for the hypertriglyceridemia were associated with higher rates of multivessel CAC. With further adjustment for demographic and cardiac risk factors, the same dyslipidemia groups were still associated with multivessel CAC, even after controlling for the total CAC score. An earlier study by Paramsothy et al. Similar to Paramsothy et al.
These findings suggest that an isolated elevation in triglyceride levels may not be a pathologic risk factor for subclinical atherosclerosis, although hypertriglyceridemia may still be an important factor in cardiovascular disease. The hypertriglyceridemia group in this study also had a relatively high HDL-c of The prevalence of low HDL-c group and adjusted risk factors were identical in both studies.
Multivariate logistic regression revealed that HDL-c is predictive of calcified plaque development independent of LDL-c. However, sensitivity and positive predictive values for HDL-c were low [ 18 ]. Furthermore, Noda et al. They found that HDL-c cholesterol levels were more accurate for diagnosing the presence of high-risk coronary plaque with areas under receiver operating curve AUC of 0.
This may explain the significance of HDL-c levels found in our study, since, unlike Paramsothy et al. Combined hyperlipidemia, simple hypercholesterolemia, and participants with MetS had significantly increased risk of multivessel involvement of the coronary arteries in patients with subclinical CAD [ 20 ].
This is in line with Paramsothy et al. Given these findings, elevated LDL-c seems to be the principal determinant of CAC prevalence and its extent, with high TG levels having less influence [ 6172021 ]. Of notice, in the multivariate analysis, the confidence interval of the combined dyslipidemia group is rather wide because the numbers of participants with this disorder are relatively small, 3.
Atherogenic dyslipidemia is largely underdiagnosed and undertreated in clinical practice per the findings of Fruchart et al. Male gender is a recognized independent risk factor for coronary heart disease by the Framingham Risk Score. In addition, in their study of participants, McClelland et al. The same study showed that calcium amount and prevalence were steadily higher with increasing age and in Whites, whereas Asians had the highest ratio of multivessel CAC in our study.
Coronary artery calcium, a known marker of coronary atherosclerotic plaque, has been consistently associated with cardiovascular morbidity and mortality [ 215172324 ]. The clinical significance of the demonstrated association between dyslipidemia types and the extent of CAC, controlling for CAC score, remains unclear.
Although the absence of CAC is not reassuring in symptomatic patients, the CAC score may be associated with myocardial perfusion defects in asymptomatic patients.
Mechanisms of hypercholesterolemia and atherosclerosis.
Studies have shown that CAC burden and extent predict future coronary revascularization procedures [ 24 ]. As Budoff et al. Independent predictors of coronary artery bypass graft versus percutaneous coronary intervention included three- or four-vessel CAC, higher CAC burden, and involvement of the left main coronary artery. The significant association between dyslipidemia types, except hypertriglyceridemia, and the extent of CAC may prompt more aggressive treatment and prevention of elevated LDL-c, low HDL-c, combined hyperlipidemia, and MetS.
Simple hypercholesterolemia may have the greatest impact in determining the severity of atherosclerotic disease, especially in those with diabetes and taking lipid-lowering medications. As others have shown, LDL-c is the dominant lipid determinant of atherosclerotic disease [ 617 ]. As the MESA study gathered data from a large, multiethnic population, the results may be widely generalizable. The imaging and laboratory procedures were standardized at a common institution.
What is Familial Hypercholesterolemia? | The FH Foundation
Our study also has several limitations. Although we attempted to adjust for all possible confounding factors in our model, the residual confounding by unevaluated factors cannot be completely ruled out. As we examined cross-sectional associations, the possibility of temporal and selection biases may exist.
Participants on statin therapy and with diabetes were excluded because these factors could potentially misclassify the lipid categories and confound the relationship between dyslipidemia and CAC. We used the term dyslipidemia compatible with metabolic syndrome instead of dyslipidemia of metabolic syndrome.
To define this category, we did not factor in obesity or blood pressure to isolate the impact of dyslipidemia on the extent of subclinical atherosclerosis. The results of this study further elucidate the role of CAC in cardiovascular disease. Clinicians already use the CAC score to predict future cardiovascular morbidity and mortality in asymptomatic patients with moderate risk factors. Recognizing the extent of coronary artery calcium may provide additional information beyond whether or not atherosclerotic disease is present.
The association of dyslipidemias with CAC extent is further evidence in support of the importance of dyslipidemia, especially simple hypercholesterolemia, as a target for therapy. The association between multivessel coronary artery disease and the cardiovascular risk factors, including dyslipidemia, had been widely studied in patients with documented clinical CVD, using invasive coronary angiography [ 2728 ]. Our study is novel to address this relationship, assessed by cardiac computed tomography, in a large multiethnic cohort free of clinical CVDs at baseline.
We believe the underlying mechanisms of these associations should be relevant to disease prevention and require further investigation. Furthermore, the current findings may explain the difference when comparing the results of different studies.
For instance, in patients with low HDL-c, although the CVD risk is high independently of other cardiovascular risk factors, the clinical trials have shown lack of improvement in the cardiovascular outcome when using drug therapies to boost the level of HDL-c. Our observation highlights the fact that the relative impact of low HDL-c, and potentially the targeting pharmacotherapy, on CAD extent may vary depending on the population selected, low versus high calcium score.
Similarly, CVD outcome studies with triglyceride-lowering agents have produced inconsistent results, meaning that no convincing evidence is available that lowering triglycerides by any approach can reduce mortality. The association between plasma TG levels both fasting and nonfasting and CV risk is often attenuated once adjusting for other lipid parameters.
However, it is worthy to notice the lack of association between high TG level and CAC extent existing in our study even prior to adjusting for other lipid parameters. A number of studies have found that the association between plasma TG levels both fasting and nonfasting and CV risk is often attenuated once adjusting for other lipid parameters, including HDL-c and non-HDL-c.
An analysis conducted by the Emerging Risk Factors Collaboration demonstrated that there was a significant and stepwise association between fasting and nonfasting TG levels and CVD risk. Elevated TG levels are closely associated with higher levels of non-HDL-c and apoB and low levels of HDL-c, and this may explain why this association is weakened after adjustment for these parameters. This is inherent in the study design since we classified the study cohort into 6 mutually exclusive dyslipidemia categories.
Further research is needed in examining coronary artery calcium extent, not simply the score, as a potential tool in prognosticating, treating, and perhaps preventing subclinical atherosclerosis in otherwise low-risk populations. Other lipid parameters such as non-HDL-c and lipoprotein a Lp a have been proposed as independent risk factors for coronary heart disease and their impact on the extent of multivessel CAC needs to be explored further.
These groups account for the complexity of having more than 1 abnormal lipid parameter in the individual patients. It is challenging to create another mutually exclusive group by using non-HDL-c cutoff because this parameter encompasses all of the circulating atherogenic lipoproteins, including LDL-c. Furthermore, the aforementioned study included participants with diabetes and lipid-lowering medications, whom we excluded in the current analysis, to avoid the effect of these 2 factors on lipid parameters and CAC.Physiology of Lipoproteins Cholesterol
Genetic studies and multiple epidemiologic studies have identified Lp a as a risk factor for atherosclerotic diseases such as coronary heart disease and stroke [ 31 ].
In a previous study of outpatients, Jug et al. In another study by Cho et al. Whether adding the extent of CAC, single versus multivessel CAC, to the absolute calcium score poses any incremental therapeutic value needs to be tested in a large population-based cohort. Conclusion In a population-based cohort, the extent of multivessel CAC was associated with different dyslipidemia types except for hypertriglyceridemia.
The results were still significant even after controlling for CAC score.