Cardiometabolics in Children or Lipidology for Kids Stanley J Goldberg MD Diplomate: American Board of Clinical Lipidology Tucson, Az
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Death Risk Approximately 40% of the US population die as the result of Cardiovascular Disease
Question #1 DOES ATHEROSCLEROSIS START IN CHILDREN?
Korean War Autopsy Series 300 autopsies - 73% had some coronary atherosclerosis Mean age = 22.6 yrs 6% had severe lesions 50% or greater narrowing Enos WF, JAMA: 152:1090-93. 1953
Viet War : Autopsy /Coronary Lesions/ US Soldiers 105 autopsies for coronary lesions Mean age = 22.1 yrs 45% had some coronary atherosclerosis 5% had severe Lesions McNamara JJ, JAMA 1971;216(7):1185-1187.
Bogalusa Heart Study 93 deaths with full risk factor data % of patients with with fibrous Coronary Artery plaques by age Berensen G et al NEJM 338:1650-7 1998
Question #2 IS ATHEROSCLEROSIS MORE COMMON IN CHILDREN WITH CVD RISK FACTORS?
Bogalusa: % of total Intima covered by plaque vs # of risk factors But atherosclerosis is never uniform through a vessel
QUESTION # 3 SINCE ATHEROSCLEROSIS STARTS IN CHILDREN, SHOULD WE SCREEN FOR RISK FACTORS IN CHILDREN?
NHLBI Pediatric Screening Recommendations Selective screening of Lipid Profile >2 years of age Universal Screening of Lipid Profile : 9-11 years of age 17-20 years of age every 5 years thereafter Endorsed by: American Academy of Pediatrics American Heart Association National Lipid Association Pediatrics 2011; (Suppl 5) S1-S44
Hetrozygous Familial Hyperlipidemia (FH) was the Original Focus For Screening FH is a loss of function of the gene for the LDL receptor Criteria: Simon-Broome and Dutch Lipid Clinic Suspect FH In children when LDL C > 156 mg/dl 156 high sens, low spec, 190- low sens, high spec Incidence is 1:200-250 in general population Special Populations- incidence is 1:67 Genetic test available with 50% + detection
Is FH Worth Screening For? 1. Mortality for Myocardial Infarct in FH is : 100 X greater than non-fh at ages 20-39 years 4X greater at ages 40-59 years 2. Those with untreated FH have a dramatic increase in coronary vascular disease after 20 years of age 3. Early treatment appears to avoid coronary vascular disease Rx is with statins, ezetimibe, resins, PCSK9 antibodies
Identification of FH Patients by country
Cascade Screening (save a parent, grandparent or other family member) FH is a dominant with very high penetrance Once a patient with FH is identified it is imperative to screen up and down the family tree of the index patient and index case and siblings.
Screening Also Will Detect other Lipid Abnormalities: A. Cholestertol Hyperabsorbers B. Dysfunctional LDL Receptor C. Metabolic Syndrome D. Genetic Triglyceride Disorders E. Low HDL F. Rare Genetic Disorders G. Adverse Reactions to Meds (e.g. acne treatment)
Control of Blood Lipids Normal Value Genetic Control Diet Control Exercise control LDL <100 mg/dl Trigs <90 mg/dl HDL >40 M >50F ++++ +? ++ +++ +++ + +++ ++
NHLBI Lipid Recommendations But where did it come from? Pediatrics 2011; 128:S6 TO AGE 19 Acceptable Borderline High LDL <110 110-129 >130 HDL >45 Trigs <90 90-99 =/>100 20-24 YEARS LDL <120 120-159 >160 HDL >45 Trigs <115 115-149 >150
TIP: FAMILY HISTORY IS VERY IMPORTANT
Other Genetic Dyslipidemias for Kids 1. 10% of population have elevated Lipoprotein (a) 2. 12.5% have cholesterol hyperabsorption (gut) 3. 1-2% have diabetes type 1,2 4. 3% have other genetic dyslipidemias: HeFH, hofh, ARH, gain of function PCSK9, LAL-D Lipoprotein lipase polymorphisms, many others 5. 20% have Metabolic Syndrome due to intraabdominal fat distribution which is determined by genetics.
A New Genetic Factor Association of Maternal Prepregnancy Dyslipidemia With Adult Offspring Dyslipidemia in Excess of Anthropometric, Lifestyle, and Genetic Factors in the Framingham Heart Study Michael M. Mendelson, MD, ScM; Asya Lyass, PhD; Christopher J. O Donnell, MD, MPH; Ralph B. D Agostino Sr, PhD; Daniel Levy, MD CONCLUSIONS AND RELEVANCE Adult offspring dyslipidemia is associated with maternal prepregnancy dyslipidemia in excess of measured lifestyle, anthropometric, and inherited genetic factors. The findings support the possibility of a maternal epigenetic contribution to cardiovascular disease risk in the general population. Further research is warranted to determine whether ongoing public health efforts to identify and reduce dyslipidemia in young adults prior to their childbearing years may have additional potential health benefits for the subsequent generation. JAMA Cardiol. doi:10.1001/jamacardio.2015.0304 Published online March 2, 2016.
Maternal pre-pregnancy LDL
Metabolic Syndrome Criteria for Adults Waist women > 34.5, Men >40 inches Blood Pressure =/> 135 systolic or >85 diastolic HDL <40mg/dl male or <50 mg/dl female Triglycerides =/>100 mg/dl Fasting glucose >100
Relationship between Waist Circumference and Visceral Adipose Tissue Accumulation Subcutaneous adipose tissue Visceral adipose tissue Front Visceral Adipose Tissue (cm 2 ) r = 0.80 60 80 100 120 Waist Circumference (cm) Pouliot MC, et al. Am J Cardiol. 1994;73:460-468; Després JP, et al. BMJ. 2001;322:716-720.
Powerful Central Obesity Detector
Waist/Height Ratio =<.5 = very low probability of MS.5-.6 = Moderate probability of MS =>.6 = very high probability of MS Example 1: waist -31 and height -62 =.5 Example 2:waist -37.2 and height -62 =.6 Khoury et al. J Am Col Cardiol 2013. 62:742-751
Waist/Height Ratio 140 Triglycerides >.6 Fasting Glucose mg/dl 120 100 80 60 40 <.5 mg/dl 95 94 93 92 91 <.5.5-.6 >.6 20 90 0 Waist -Height Ratio 89 Waist/Height Ratio mg/dl 56 54 52 50 48 46 44 42 <5 HDL.5-.6 >.6 IU/ml 25 20 15 10 5 Serum Insulin.5-.6 <5 >.6 40 0 waist/height ratio waist/height Ratio
Carotid IMT
Vijasarthi A, Goldberg SJ Journal of Lipids Volume 2014, Article ID 546863, 7 pages
Metabolic Syndrome- 14 y.o. boy Combination Visceral obesity Increased SQ fat Gynecomastia Note belt position
Change with time Visit 1 Visit 2 Visit 3 Visit 1.5 yrs BMI 34.1 32 31.2 27.2 TSC 232 188 174 176 LDL --- 101 110 114 HDL 28 30 38 42 Trigs 448 283 136 102 Waist (jnch) 44.5 41 38 37 W/H Ratio.66.60.55.53 ALT 224 196 44 28 Glucose 108 104 100 96
How many overweight kids are there??
A Sudden Heart Attack Never Occurs It Takes Years of Preparation
10 yo boy showing LDL change with decreasing Triglycerides 400 350 300 250 200 150 LDL Triglycerides 100 50 0
% LDL Response to Ezetimibe 1/8 of the population does not have haplotype 1735C-25342A-27677T for NPC1L1 gene Hegel RA et al. Lipids in Health and Disease: 2005,4:16
18 year old girl 1. Elevated LDL 142 2. Family history of increased LDL, T2D, MI 3. Mom demanding statin therapy 4. Mild central overweight 5. Uses celexa for anxiety 6. Excessive carbohydrate intake
High LDL + increased waist size 1 st Visit Zetia + Diet BMI 27.2 25.8 TSC 225 164 LDL 142 93 HDL 55 57 Tri 138 71 Wt 149# 141# Ht 62 in 62 in Waist 37 35.4 W/h.59.57
> 2000 persons, ages 15-34 years Atherosclerosis begins in childhood with the appearance of aortic fatty streaks as early as 2 years. Coronary fatty steaks begin to form in adolescence Most persons have coronary fatty streaks by the age 20-29 years. Am J Cardiol. 1998 Nov 26;82(10B):30T-36T.
At 0-18 years, normal fasting triglycerides are: 1. =/<250 2. =/< 150 3. =/ < 90 4. =/< 125 5. =/< 70
Criteria for Metabolic Syndrome include all the following except: 1. BP 2. Waist circumference 3. Triglyceride level 4. HDL Level 5. BMI 6. Serum Glucose
Heterozygous familial hyperlipidemia has a worldwide population frequency of: 1. 1/1,000,000 2. 1/100,000 3. 1/1000 4. 1/200-250 5. 1/67
In the Netherlands 87% of patients with Hetrozygous Familial Hyperlipidemia (HeFH) have been identified. What is the estimated % of HeFH identification in the USA? 1. 60% 2. 95% 3. 25% 4. 10% 5. <2%
The good news is you passed Security, the bad news is you have too much intra-abdominal fat