Coronary Risk Factors & Hypertension (M/A)

Coronary Risk Factors in Children (MA75)

ATHEROSCLEROSIS

-CAD is the #1 cause of M&M in developed countries

-CAD & stroke make up >70% of heart dz in US

-New evidence shows that athero starts as a child

= lipid and cholesterol deposits in intima of art wall--> fatty streak w accum of lipid filled macros in the intima. These are flat so no obstruction to the lumen. Then--> raised plaques as more lipid and macros accum and fr sm muscle cell prolif. THe sm muscle cells form a fibrous cap over the necrotic debris, cholest crystals, and Ca'ion of the art wall that dvps. The raised lesion--> incr risk of MI bc of obstruction to the lumen. If they rupture--> release thrombogenic substances fr the necrotic core.

Risk Factors:

-Non-Modifiable

-age, male sex, FHx

-Modifiable

-dyslipidemia, htn, DM, smoking, obesity/metabolic synd, coagulation factors

-Possible R/F

-Inflmn, incr CRP, SES, ethnicity, phys activity/fitness, diet

Imaging

-Hard to image.

-Adults can get CT to check for Ca deposits in cor arts, which is assoc w worse M&M...

-in young adults in one study 30% men, 10% women already had Ca deposits

-R/F for Ca = SBP, BMI, LDL, cholest, HDL --> strongest R/F

-childhood wt, BMI, DPB, cholest as young adult also assoc w incr risk

-MRI- can show plaques and supravalvar AS

-high res multicontrast MRI can show if the art plaque is unstable/may rupture

-US- Carotid Artery Intimal-Medial Thickness (IMT) is useful to eval athero.

-IMT is assoc w CV R/F and MI & stroke incidence

-In men, childhood total cholest and TG were assoc w carotid IMT

-In women, childhood wt, BMI, TC, and TG were assoc w carotid IMT

-diff study showed childhd LDL, cholest LDL=C, SBP, BMI, smoking all incr young adult carotid IMT risk

Risk Factors:

Diabetes

-w incr obesity--> incr DM2 in kids

-adults: DM2 causes more renal failure and preiph vasc dz than anything else

-5x incr risk of CV dz in pts w DM compared to others w/o DM

-70% of pts w DM dz die of CV dz

-10 year mortality rate of DM pt is 10x higher than non-DM pts, and most die fr CAD

-DM = CAD Equivalentfor risk of the M&M

-In teens w DM2, not entirely sure of CV dz risk, but likely will get CV dz by 30-40s if the time period is similar to that of adults bn DM and CV dz.

Smoking

-Major Independent risk factor for CV dz

-Stopping smoking can provide benefit w decr in CV and lung dz risk

-decr risk of of CV dz starts in the 1st year after stopping, and continues for up to 3 years after

-Teens- by 15yr old it incr athero lesions if smoking

-incr LDL and decr HDL

--> endothelium injury--> nidus for athero

-Smoking declined in teens during late 90s/early 2000s, fr 27% to 22%, but has increased in girls (now = % of girls and boys smoke)

-if parents stop, teens are less likely to start

Obesity, Metabolic Syndrome

-Overweight child prevalence has tripled fr 1980 to 2002

-16% of US kids/teens are overweight

-Assoc w CV dz R/F - dyslipiddemia, htn, LVH, athero, OSA

-Follow BMI

-Overweight = >95%ile

-At risk for overwt is 85-95%ile

-Metabolic Syndrome =

-obese (centarl obesity espec)

-dyslipid = incr TG, decr HDL

-htn

-hyperInsulinemia

-Impaired gluc metabl

-inflmn

-prothrombotic factors

Physical Activity

-CV fitness (lack of it) is an adult CV dz risk factor

-Weak assoc bn phys activity and lipid/lipoportein levels, but strong assoc w HDL levels

-results inconsistent bn level of activity and lipid levels in various studies, likely bc each had a diff level of phys activity studied...

-it appears tha a minimum of 40minutes of activity/day x5days/week for 4 months is needed to lower TG and incr HDL

-Isometric/resistance exercise may also incr HDL- one study showed improved HDL and LDL in 9yo boys after resistance training

-No clear assoc bn lower BP in kids and exercise, but in teens w htn aerobic activity programs for 12-32 weeks have lowered BP. Strength training has little effect on BP in kids w htn

-Thus, kids/teens w essential htn should do aerobic activity regularly

LIPIDS & LIPOPROTEINS

=organic compounds not soluble in water

-lipids needed for cell membranes and for some hormones

-plasma lipids- transported by lipoproteins

-include cholesterol, TG, and phospholipids

-apolipoproteins - proteins that combine w the lipids

-A-1, A-II, B-100, C-11 are the major ones

-fx: -bind w R' on cells

-cofactors forex in lipid metab- lecithin cholest acyltransferase, and lipoprotein lipase

-structural protein for biosynth and plasma liporotein secretion

-Apo A-1 needed to synth HDL...

-4 Types of Lipoproteins:

-chylomicrons - TG rich particles made by GI tract, the biggest lipoproteins

-fx to transport cholest/TG fr GI to storage/metabolism sites

-usually absent in fasting pts, and clear quickly after the meal

-clear via lipoprtn lipase--> remnants of chylomicrns which are atherogenic but cleared by liver

-VLDL - relatively large particles, made by liver to transport TG/cholest (made by liver) to periphery

-LDL - the major carrier of cholest to periph tissues; smaller particles

-45% cholesterol

-very atherogenic

-LDL binds to R' on cell wall, and are then internalized into the cell

-75% of LDL is removed fr bld by binding to the R', rest by macros

-HDL - made by liver & by GI tract, and by catabolism of chylomicrons and VLDL

-HDL2 is the most protective type against athero

Epidemiology

-Estimate: for each 1% incr in cholest--> 3% incr in risk for CV dz

-and higher HDL is assoc w lower risk of CV dz

-saturated fat intake effects cholesterol levels

-high/low LDL/HDL levels as a child is assoc w same as an adult

-while childhood cholest levels are important in later cv dz, obesity, smoking, OCP use has bad effects on levels as an adult

-In one study, of kids with high cholest (>75th%ile) only 75% (girls) and half (boys) would have high enough levels as an adult to warrant treatment --> so high cholest levels as a child is not Sp for adult levels

--> thus some say use only targeted screening for +FHx for dyslipidemia or CV dz, and not universal

Factors Causing Dyslipidemia:

Genetics

-Familial Hypercholesterolemia-

-LDL R' xx --> mutations that cause the R not to fx, or not to be placed on the cell membrane, or unable to trigger endocytosis once binded to the LDL ==> high LDL levels in plasma

-homozygous familial hypercholest is uncommon -1/1million, but geterozygous form is 1/500!!

-hetero--> total cholest >300, LDL >240 as a child, then fall some at puberty

-->rare to have xanthomas, risk of CAD by 30-50yo

-homozygous--> TC 600-1000, LDL 450-850

-->xanthomas at extensor surfaces by 5yo, CAD by 10-20yo, and often AS

-HDL xx--> low HDL fr abNl metabolism of HDL and it's major apolipoprotein APo A-1

-+/- premie CAD

-TG xx--> Familial hypertriglyceridemia - auto dom; expression quicker if obese

-lipoprotein lipase defic (rare)--> hi TG, can --> pancreatitis, and neurologic Sx

-Tx- very low fat intake bc the chylomicrons depend on intake of fat in diet

-Familial combined hyperlipidemia- incr cholest and TG [ ],

-Lipoprotein- similar to plasminogen, made of LDL+ApoB100- high levels is assoc w CV dz, plastma levels are inversely assoc w the molecular wt of the Apo component. ...

Diet

-fat and cholesterol in plasma are affected majorly by dietary cholesterol, espec saturated fat

-saturated fat & cholest come mainly fr animal based foods, but also palm oil and some other plant oils are high in saturated fat

Secondary Causes of Cholesterol Elevation

-DM1 - high TG, bc defect in VLDL lipolysis bc of inhibition of lipoprotein lipase & hepatic lipase

-DM2 - high TG, bc overproduction and defective lipolysis of VLDL TG's

-improved DM1 & DM2 control--> less lipid xx

-Hypothyroid - high TG & LDL, bc of LDL R' suppression & too much VLDL synth

-check for thyroid xx if lipid xx; Tx of hypothyroid will help lipid xx

-Nephrotic Syndrome - high TG & LDL, bc too much VLDL synth

=proteinuria + low albminemia +edema + high cholest (high LDL cholest mainly, also TG)

-low albumin--> liver increases protein synth, including apolipoprotein synth, so more hepatic cholest synth--> down regulate LDL R' in the liver--> decrease rate of LDL-C removal from circulatin

-Tx of the nephrotic syndrome will Tx dyslipidemia

-also, liver dz, obstructive jaundice, infection, obesity all --> abNl cholest levels

-Chronic Renal Failure pts are at high risk for CV dz- see high TG & low HDL-C (up to 30% pts)

-hyperTG'emia of uremia is bc of defic in lipoprotein lipase or hepatic lipase

-So, must Tx CRF pts w lower saturated fat, cholest, simple sugars, & incr phys activity

-Meds can incr lipids- estrogen/pregestin OCPs--> incr TG; retinoic acid--> incr TG, anabolic steroids --> incr LDL and lower HDL

-Acute & Ch Infection can --> dyslipidemia- can affect HDL & apolipoprotein, so don't check for another 2 weeks after acute infection

Metabolic Syndrome

-Increased waist circumference & atherogenic dyslipidemia w incr TG and low HDL

-have insulin resistence often

-see high level of insulin w fasting

-Tx w wt loss/exercise...

Clinical Recommendations:

Population Approach

-lower level of childhood LDL continued into adolescence/adulthood--> less risk over time

Diet - <2yo needs saturated fats...;

-Above 2yo:

-Daily Calorie Intake: 20-30% Fat

-lean meats 5-6oz/day

-low-fat dairy 24-32 oz/day

-limit eggs to <2-4/week

-largest part of diet should be whole grain, cereal, produce- high fiber/low cholest/fat

-Cereal/Fruit Juice xx- simple sugars; can --> incr TG's

-also w snaks/sodas...

Individual Approach

-ID persons at higher risk for future CV dz and then Tx them

-FHx of CV dz or high cholesterol

-but many kids w high cholest would be missed if use FHx alone (30-60% missed)

-Total & LDL cholest decline at puberty, so some teens will appear Nl but really will have high levels after puberty

-limited data...

Tx:

-increase phys activity

-diet changes

-if kid w high LDL, must be more aggressive w diet w <7% daily calories fr saturated fats, and <200mg/day of cholest (!) ==> decr LDL by 4-14% (???significant???)

-diet change was shown effective at lowering LDL...

-Fiber can also help- plant stanol & sterol esters

Rx Tx-

-Bile Acid Binders

-not absorbed, only xx is GI xx - reduce by taking w water/fiber

-hard for kids bc powder form is gritty and must be mixed w liquid, and tablets are large

-can lower LDL by 13-20%

-Cholesterol Absorption Inhibitors

-Ezetimibe blocks cholest abs

-not studied in peds well

-decr LDL by 20% in adults

-in adults, used w statins to get additional cholest lowering effect

-better than bile acid binders bc less xx, easier to take

-HMG-CoA Reductase Inhibitors

-Statins

-competitively inhib mevalonate synth by HMG-CoA Reductase--> can't synth cholest in liver

-lower LDL, prevent CV xx in adults

-safe & effective in kids/teens, but no long term studies

-xx = incr LFTs & Cr kinase; myositis which can become rhabdomyolysis, so assess for abNl muscle ache/cramps and then if + check Cr kinase level and stop Rx...

-Teratogenic!!, so ensure contraceptive use of sexually active...

HYPERTENSION

Epi:

-R/F for adult CV dz - MI, CVA, LVH, CHF

-10mmHg incr in SBP assoc w 20% incr risk of CV event as adult age 35-64yo

-1y htn is #1 cause - ?mech, but clusters in families so in part genetic

-maybe bc of incr Sn to dietary Na or incr Renin angiotensin aldost activity, or incr symp N sys

-2y htn- renal parenchymal dz, CoAo, Renal art stenosis, other

-Adults- 92-95% of htn is essential htn, and 90-95% of peds/teen htn is also essential htn

-Htn Definition in kids- >95%ile over time

-Peds Prevalence- 1-5% of kids/teens

-avg BP may be increasing in peds population over time- more recent surveys show higher BP than b4.

-at least in part bc of incr in BMI

-BMI is the strongest determinant of BP in kids

BW & BP

-BW may be an important determinaent of BP later in life- LBW bc fetal undernutrition would have decr renal mass/changes to vasc structure/fx--> later incr risk of htn (one theory)

-One study shows LBW assoc w higher BP at 22yo

Tracking

-= tracking an individual on his own BP curve (like wt...) bc wide range of Nl...

-High BP at one age would be assoc w high BP at later age, though BP at one age isn't accurate for later age (like height), but multiple BP measurements taken over several years does improve accuracy

-Bogalusa study--> of adults w htn, >40% had been in the top 20% of distrib BP as kids,

-kids who maint a high BP over timea re usually taller, w more adiposity, and greater bone age, and more advanced pubertal dvp than their peers

Target Organ Effects

-less clear whether htn as child is related to dvp of CV dz, though severe BP elevation (often due to 2y htn), can --> CV dz, hypertensive encephalopathy, CHF, death; much less certain if milder htn are ssoc w CV xx

-Bogalusa study--> early stages of atherosclerosis is assoc w incr BP- assoc w incr LV mass in kid/teens, and LVH is an independent R/F for CV dz as an adult

Normal BP

-taken fr large epi studies in kids

-taken w pt in sitting position, using auscultation; for ppl <1yo it's taken in supine position w an oscillometric device

-BP incr w age, ht, and does correlate w BMI (but this correlation is considered a pathology...)

-males have higher BP than females

-the diff increases w age

-ethnic diffs in BP are minimal as child/teen

Ambulatory BP

-the tables for BP norms are taken while sitting, so don't reflect actual fluctuating BP w standing etc, and also are affected by white coat effect...

-Ambulatory BP monitoring = wear portable device for a day to check BP throughout the day

-may be more Sn to assess for risk for target organ damage...

-can see a 10% decline in BP w sleep at night; no dip in BP at night ias assoc w higher future BP, incr risk of target organ damage, and some 2y forms of htn

-may or may not be good for peds...

Hypertension Definition

-must have BP >95th%ile on 3 separate occasions

-if severely elevated, then must do more acute Dx/Tx

BP Measurement

-Neonates:

-indwelling a-line is the best

-alt- oscillometric monitor (they do correlate well w a-line under controlled circumstance, but clinically they have wide variability compared to auscultation ad to other osc. machines

-Best to check at arm, bc leg BP can be higher; no Nl standards avail for leg

-no need to check BP routinely in infants; only check if other concern...

-Children/Teens

-Check at 3yo and older w each annual visit

-Check by auscultation - R arm preferred w pt seated quietly, arm at heart level

-Do check at all well and ill visits

-Cuff Size- the bladder width should be at least 40% of arm circumference at the pt midway bn the olecranon and the acromion

-the bladder length should be bn 80-100% of the arm circumference so that it encircles it

-thus bladder width:length ratio should be at least 1:2

-if the cuff available is too small, use the next larger cuff...

-Korotkoff phases

-Phase 1 = Onset of tapping - pt used for SBP

-Phase 5 = Disappearance of the sound = DBP

-if the sound can be heard to 0mmHg, then the onset of Phase 4 = muffing of sound, should be used for DBP (!)

-Oscillometric devices not rec for routine BP check in kids/teens, but if used you should confirm it w a mercuray manometer or aneroid device (an alt to Hg device)

Hypertension Etiology

-the younger the pt and less FHx and higher the BP, the more likely it is 2y htn

Neonatal Hypertension

-Renal parenchymal dz, Renovascular, CV, Endocrine, Rx, Neoplastic xx, and bronchopulmonary dysplasia and incr ICP

-check 4extrem BP to r/o CoAo

-check if h/o umbilical art cath- ? vasc trauma w renal art stenosis

-check BUN, Cr for renal fx, check urine for renal parench dz

-CXR & Echo if poss CHF

-US of GU tract if possible renal/urological xx

-if all are negative, then check arteriogram to r/o renal art stenosis (and mid Ao syndrome)

-check for BP in neonates w:

-premie neonatal xx

-CHD

-Renal/Urological dz

-Incr ICP Sx

-Rx Tx that can incr BP

Childhood/Teen Hypertension

-Evaluation:

-H&P- sleep Hx, FHx, R/F, diet, habits (smoking/EtOH)

-BUN, Cr, electrolytes, u/a, UCx - r/o renal dz & ch pyelonephritis

-CBC - r/o anemia, consistent w ch renal dz

-Renal US - r/o scar, congen xx, disparate renal size

-Assessing Target Organ Damage fr Htn

-Echo to look for LVH- assess LVED dimension, IVS thickness, LVPW thickness

-LV Mass (grams) = 0.8[1.04(IVS+LVED+LVPW)^3 - LVED^3 +0.6

-LV mass very dependent on body size, esec lean body mass so we index it to ht^2.7 to acct for pt's lean body mass and exclude effect that obesity may have on the BP

-99%ile of Nl is <51g/m^2.7, and is used as a cutoff pt; higher LV Mass is assoc w more M&M in adults

-US Carotids- not rec for kids/teens

-Urine microalbuminuria assessment- not rec for kids/teens

-May check Ophtho exam for retinal xx

-should aslo check for dyslipidemia and DM, and if sleep xx for OSA, and c/s drug screen

Tx:

-Lifestyle Modification

-diet, phys activity

Diet- overweight can incr BP; too much NA, EtOH, to little K all assoc w incr BP, but uncertain if improvement will really effect BP in kids/teens

-Though, in kids/teens, much of the 1y htn is at least in part due to wt

-It seems that some are more Sn to salt than others, but no simple way to check ea pt

-best diet is the "DASH" diet has much produce, low fat dairy, whole grain, poultry/fish, and nuts

shown to reduce BP in pts w htn by 11.6mmHg for SBP, 5.3mmHg for DBP

Physical Activity- unsure if it is an independent factor for htn

Rx Tx

-goal to lower it to <95%ile, but be more aggressive if +DM/ch renal dz and goal <90%Ile

-Prefer diuretics and beta blockers as first line in teh ALLHAT trial study in adults

-Peds studies have not compared diff classes of Rx for htn, so no evidence for kids as to which Rx to pick

-must specify for ea pt...

-ACEI or betablockers for DM or proteinuric dz, but note they are teratogenic for females teens

-betablocker if pt also gets migraines bc it can help w that too

-start low initially and titrate up