Friday, March 21, 2014

Kawasaki Disease and Cholesterol




I very often get asked specific questions about Kawasaki Disease and __________. While I feel that my DSK Kawasaki Disease Resource List is very useful, it can sometimes get overwhelming to try and find a lot of information on one very narrow subject.  So I'd like to start having in depth posts that give as much information as I can wrestle up on a subject and give everyone a chance to weigh in with their opinions. Let's see how it goes!

I was recently asked if there are specific statistics on how many KD kids are diagnosed with high cholesterol. The short answer is... yes. The long answer is... it's way more complicated than a single statistic. So complicated that I didn't feel like I covered my bases until I had 20 links to share with you. And this is just breaking the tip of the iceberg.

I've arranged the sources in chronological order; I feel it is a fair way to organize them and I like the timeline feel. I'm not giving an opinion of what I think about the information. I've tried to give a balanced amount of information and include different viewpoints that are available. You will notice that many of these articles may sometimes contradict each other. I don't like to try and sway anybody. I'm seeking answers just like you are. And I always like to hear as many sides as I can! I also assume that you all feel the same way.


Many of these links are specifically about KD and cholesterol, many are about kids and cholesterol, and many are just about cholesterol. The last two are about the very latest findings in regards to KD and heart disease in general.  I find each one gives me a better understanding of how to proceed with my KD kid. OK, here we go.

1.  "There was no correlation between the serum cholesterol concentrations and coronary artery abnormalities. These data lead us to infer that KD does not cause such permanent changes in cholesterol metabolism as to be considered a risk factor for atherosclerosis beyond that caused by the disease itself.” 1991, Source: http://www.ncbi.nlm.nih.gov/pubmed/1919886

2.  "We found that Kawasaki syndrome is associated with significant abnormalities in lipid profile. In the earliest days of illness, mean plasma concentrations of total cholesterol and HDL cholesterol were profoundly depressed, whereas mean triglyceride concentration was very high. Total cholesterol values rapidly returned to normal and remained stable more than 3 months after the onset of illness. HDL cholesterol concentration recovered more slowly after illness onset, and mean HDL cholesterol concentration was significantly lower than expected, even in the period, more than 3 years after illness onset. The lipid findings early in the course of Kawasaki syndrome are consistent with those delineated in a variety of acute infections. Both acute bacterial and viral infections are associated with diminished concentrations of low density lipoprotein and HDL cholesterol and with increased concentrations of very low density lipoprotein cholesterol, at least in part attributable to concurrent reductions of lipoprotein lipase and hepatic lipase activities. Altered lipid profile has been demonstrated to be related to the actions of a variety of structurally distinct cytokines (e.g., tumor necrosis factors, interleukins, interferony) released during the host response to infection. The changes in lipoprotein metabolism after acute infections are temporary, although recovery of lipid profile has been reported to be delayed as long as 1 month after disease onset in 80% of patients.23 The persistence of low HDL cholesterol for many years in our sample suggests a more lasting effect of Kawasaki syndrome on endothelial function, perhaps attributable to diminished activity of lipoprotein lipase. This enzyme resides on the capillary walls of most tissues and functions at the luminal surface of the vascular endothelium.” 1991, Source: http://circ.ahajournals.org/content/84/2/625.long

3.  "Lipoproteins participate in the acute response to inflammation. In animal models of acute inflammation and in adult humans with acute myocardial infarction, high density lipoprotein (HDL) levels decrease and serum amyloid A(SAA) increases and is incorporated into HDL. We previously showed that HDL cholesterol and apolipoprotein A1 (apoA1) levels are dramatically low in acute Kawasaki disease (KD) and that the decline is associated with increased SAA. In this study we prospectively assessed the time course of changes in HDL composition in children with acute KD. 12 KD children had plasma obtained before initiation of treatment; 7 had follow-up specimens obtained 2 weeks(n=6) or 6 weeks later. Total cholesterol, triglycerides (TG), HDL cholesterol total and SAA in HDL, core TG in HDL (as%), and apoA1 were measured in each specimen. SAA increased and was present in HDL acutely but not at follow-up. At diagnosis, mean total cholesterol (133 mg/dl), HDL cholesterol (20 mg/dl), and apoA1 (52 mg/dl) levels were below the normal range while core TG was increased (52%). In paired comparisons, total cholesterol, HDL cholesterol and apoA1 all increased (+29 mg/dl, p<0.05; +14 mg/dl, p< 0.0001; +48 mg/dl, p<0.0001 respectively), whereas core TG decreased by 12% (p<0.05) despite no change in plasma TG levels. These studies describe participation of HDL in the acute phase response of KD; this response includes incorporation of SAA into HDL and the recruitment of core TG in exchange for cholesterol ester in the particle. Recovery towards normal begins within 2 weeks of therapy. This is the first demonstration of the participation of HDL in the acute phase response in children.” 1996, Source: http://www.nature.com/pr/journal/v39/n4s/full/pr1996291a.html

4.  "In several reports, abnormal convalescent serum lipid profiles have been identified after the acute febrile phase of Kawasaki disease in a subset of patients. In most reports these profiles returned toward normal by 1 year after onset of the disease. Additional studies to confirm these observations are needed; for now, counseling of parents and patients should conform with standard recommendations on nutrition for children and adolescents.  For patients whose lipid profiles are abnormal, the physician may remeasure lipid levels a year later.”  1998, Source: http://www.besancon-cardio.org/recommandations/kawas-aha.htm

5.  "Subjects with low TC levels (<189 mg/dL) are at higher risk of dying even when many related factors have been taken into account. Although more data are needed to clarify the association between TC and all-cause mortality in older individuals, physicians may want to regard very low levels of cholesterol as potential warning signs of occult disease or as signals of rapidly declining health.”  2003, Source: http://www.ncbi.nlm.nih.gov/pubmed/12834520

6.  "This study demonstrates that children with a history of KD have an adverse cardiovascular risk profile long after resolution of the acute inflammatory illness. In those with coronary aneurysms, the profile is characterized by low HDL cholesterol and apoA-I levels, high apoB levels, and increased peripheral conduit arterial stiffness. In those without coronary complications, apoB levels and brachioradial arterial stiffness are likewise increased. Although the LDL cholesterol levels are higher in patients than in controls, the difference did not reach statistical significance. In addition, we did not find any significant differences in total plasma homocysteine levels and systemic BP between patients and controls.  
     Lipid abnormalities in the acute phase of KD, with decreased total cholesterol, HDL cholesterol, and apoA-I levels, are reminiscent of those in acute infection and inflammation. Although several studies have suggested that such changes are transient, Newburger et al. have reported that HDL cholesterol levels remain low as long as three years after the initial illness. The findings of the present study, performed at a mean of 7.1 years after the initial illness, agree with those of Newburger et al. and further clarify that low HDL cholesterol levels are confined to patients with coronary aneurysm formation. As the severity of vasculitis in the acute phase is, to some extent, reflected by development of coronary lesions, our findings suggest that the degree of inflammation in the acute phase may have important bearings on late lipid abnormalities.
     The changes in cholesterol and lipoprotein levels long term after KD mimic those proposed to be atherogenic. Nonetheless, the underlying mechanisms remain speculative. Endothelial dysfunction has been shown years after resolution of the acute illness. Diminished lipoprotein lipase activity with reduced generation of HDL cholesterol, as a result of endothelial dysfunction, has been proposed as a possible mechanism. Furthermore, inhibition of lipoprotein lipase may decrease apoA-I levels by increasing its catabolism. The cause for the higher apoB and LDL cholesterol levels is unknown. Nonetheless, increased LDL cholesterol levels have been described in adults with chronic inflammation due to rheumatoid arthritis. Indeed, there is increasing evidence that low-grade vasculitis continues unabated after the end of the acute phase of KD. The changes in the lipid profile in our cohort may hence be a reflection of such a continued low-grade inflammatory process.” 2004, Source: http://content.onlinejacc.org/article.aspx?articleid=1132896#bib29

7.  "All children who have had Kawasaki disease should adopt a heart-healthy lifestyle (that is, no smoking, regular exercise, heart-healthy diet) and, if needed, be treated for risk factors for adult-type coronary artery disease, such as high blood pressure and high cholesterol. Children in whom coronary enlargement was never detected return for follow-up infrequently.” 2008, Source: http://circ.ahajournals.org/content/118/7/e110.full

8.  "A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.” 2010, Source: http://ajcn.nutrition.org/content/91/3/535.long

9.  Patients who form coronary artery aneurysms of any size in the acute phase are definitely at higher risk for coronary artery disease in early adulthood and later in life. Smaller aneurysms do usually regress and appear normal after the acute phase, but risk of coronary artery occlusion in later life is still increased. Larger (greater than 8 millimeters in diameter) aneurysms remain a lifelong problem affecting normal blood flow and causing blood clots. They can also cause cholesterol plaques to form that lead to blockages. 2011, Source: http://www.cnn.com/2011/HEALTH/expert.q.a/10/05/kawasaki.syndrome.brawley/

10.  "A significant change from previous guidelines is the new recommendation that all children be screened for high cholesterol at least once between the ages of 9 and 11 years, and again between ages 17 and 21 years. The NCEP Expert Panel on Blood Cholesterol Levels in Children and Adolescents, issued in 1992, instead called for screening only children with a family history of heart disease or high cholesterol. Physicians now will be able to use a non-HDL cholesterol test that does not require children to fast; children with abnormal results should be followed up with a fasting lipid profile.”  2011, Source: http://www.aap.org/en-us/about-the-aap/aap-press-room/pages/Physicians-Recommend-all-Children,-Ages-9-11,-Be-Screened-for-Cholesterol.aspx#sthash.Bji3buo0.dpuf

11.  Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report. 2011, Source: http://pediatrics.aappublications.org/site/misc/2009-2107.pdf

12.  New Guidelines for Universal Child Cholesterol Screening. 2011, Source: http://www.childrensnational.org/files/PDF/DepartmentsAndPrograms/HLK/Cardiology/preventive-cardiology/New-Guidelines-for-Cholesterol-Screening.pdf

13.  "Arditi said the study's findings also may have implications for children with Kawasaki Disease in that they may need to be closely monitored for future development of early-onset atherosclerosis. Also, doctors treating children who have had Kawasaki Disease should closely monitor other known cardiovascular disease risk factors such as obesity, high blood pressure, high cholesterol and smoking, Arditi said.
     Atherosclerosis occurs when fat, cholesterol, and other substances build up in the walls of arteries and form hard structures called plaques. Over the course of years, plaque buildup makes it harder for blood to flow because the plaque narrows arteries and makes them stiffer. When pieces of plaque break off and move to smaller vessels, they can cause stroke, heart attack or pulmonary embolism.
     In the study, which was funded with a grant from the National Institute of Allergy and Infectious Diseases, mice with Kawasaki Disease were fed a high-fat diet and then compared to mice that did not have Kawasaki Disease but did eat the same high-fat diet. The Kawasaki mice developed significantly more atherosclerotic plaque at a younger age.” 2012, Source: http://www.sciencedaily.com/releases/2012/07/120717182957.htm

14.  "Cholesterol is a very misunderstood molecule.  And though many people might not be aware of it, there has long been a vocal minority of doctors, researchers and health professionals who believe that cholesterol and fat have been wrongly convicted as the primary promoters of heart disease. Along with many of our fellow health professionals, we believe that this emphasis on cholesterol has caused us to take our attention off what we believe to be the true promoters of heart diseases – inflammation, oxidative damage, stress and sugar.” 2012, Source: http://www.doctoroz.com/videos/cholesterol-facts-vs-myths

15.  Our finding that 5% of all young adults being evaluated for ischemia may have KD as a cause of their symptoms has important implications for adult cardiologists. The pathology of coronary lesions in patients with a history of KD is very different from the pathology of typical coronary atherosclerosis, and so optimal treatment of each is distinct.19 While typical atherosclerosis is characterized by lipid-laden macrophages, extracellular lipid droplets, and cholesterol crystals, these features are absent in coronary lesions after KD.20 Acutely, KD vasculopathy begins with endothelial cell swelling and subendothelial edema, followed by an intense inflammatory process leading to regions of myointimal proliferation with focal destruction of the internal elastic lamina, medial smooth muscle cell necrosis, and aneurysm formation,21, 22 Over time, myointimal proliferation leads to fibrous scar formation, often with calcification.” 2012, Source: http://circ.ahajournals.org/content/early/2012/05/15/CIRCULATIONAHA.111.082107.full.pdf+html

16.  "Several studies have recently found greater long-term incidence of traditional cardiovascular risk factors in KD patients. Newburger et al first demonstrated that KD patients, particularly those with persistent coronary abnormalities, have decreased high-density lipoprotein cholesterol levels long after acute illness. Cheung et al, in their follow-up of KD patients at a mean of 7 years after illness, found that patients with CAA had not only reduced high-density lipoprotein cholesterol, but also low apolipoprotein A and elevated apolipoprotein B, all risk factors for cardiovascular disease; these patients also demonstrated increased peripheral conduit arterial stiffness, indicating that they have suboptimal cardiovascular health. In comparison, KD patients without CAA demonstrated slightly improved lipid profiles, but were still found to have elevated apolipoprotein B, as well as increased brachio-radial arterial stiffness.” 2013, Source: http://www.pediatr-neonatol.com/article/S1875-9572(12)00222-7/fulltext

17.  "Professor Jeremy Pearson, associate medical director at the British Heart Foundation - which co-funded the study, said: "This analysis of existing data suggests there isn't enough evidence to say that a diet rich in polyunsaturated fats but low in saturated fats reduces the risk of cardiovascular disease. But large scale clinical studies are needed, as these researchers recommend, before making a conclusive judgement.
     "Alongside taking any necessary medication, the best way to stay heart healthy is to stop smoking, stay active, and ensure our whole diet is healthy - and this means considering not only the fats in our diet but also our intake of salt, sugar and fruit and vegetables.” 2014, Source: http://www.huffingtonpost.co.uk/2014/03/18/saturated-fat-not-cause-heart-disease_n_4984392.html

18.  "Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats.” 2014, Source: http://annals.org/article.aspx?articleid=1846638

19.  "This is the largest US study of longer-term cardiac outcomes after KD and reveals a low rate of adverse cardiovascular events through age 21. Additional validation studies, including studies with longer-term follow-up, should be performed.”  2014, Source: http://pediatrics.aappublications.org/content/133/2/e305.abstract

20.  "Study Rundown: Kawasaki Disease (KD) affects medium-sized blood vessels, is most often seen in children younger than 5 years of age, and is sometimes confused for an infectious process given its common presentation of fever. Accurate diagnosis of KD is crucial, as treatment with intravenous immunoglobulin (IVIG) and aspirin has been shown to reduce the risk of coronary aneurysm development secondary to KD’s inflammatory process. This retrospective study compared patient records from children with and without KD, and examined for differences in cardiovascular events. There was no significant difference in cardiovascular events between the two groups. Despite an overall low rate of persistent aneurysms in the KD group, cases of aneurysm development were more likely associated with an adverse event. Retrospective data was obtained from the Kaiser Permanente database, potentially underestimating adverse event data if patients obtained follow-up care elsewhere. This large study reassures the low risk of cardiovascular events in children treated for KD, though even longer-term follow-up is prudent.” 2014, Source: http://www.2minutemedicine.com/cardiovascular-events-in-kawasaki-disease-not-significantly-elevated-over-controls/ 


What are your thoughts on Kawasaki Disease and cholesterol? Comment here or come on over to DSK on Facebook and join the discussion.  Would you like to see more of these in depth articles? If so, please let me know and comment on what topics you'd like to see covered.  













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