section name header

General Reference ⬇

Nejm 1993;329:247 [women]

Pathophys and Cause ⬆ ⬇

Cause:Multiple, including elevated cholesterol (Nejm 1981;304:65); smoking, passive (Nejm 1999;340:920) and active, correlates most w pack-years not w quitting (Jama 1998;279:119); hypertension; genetic, especially in women; Hgb A1C level >5 (Ann IM 2004;141:413, 421, 475). Possibly induced by Chlamydia pneumoniaeendovascular infection in cardiovascular disease (Jama 1999;281;427, 461—though 1 wk rx w azithromycin to pts w stable CAD does not decr recurrence; Nejm 2005;352:1637, 1646, 1706), as well as vascular dementia (Jags 2005;53:583), or other causes of inflammation indicated by elevated CRP levels (Nejm 2002;347:1557, 1615; Jama 1999;282:2131, 2169) and interleukin-6 (Jama 2002;288:980); but no correlation between chlamydial IgG titers and ASHD found in women (Ann IM 1999;131:573)

Pathophys:(Nejm 1999;340:115) Wall stress causes fibrous plaques, which later infiltrate with cholesterol; impaired fibrinolysis may also play a role in genesis. Onset by age 18 yr (Nejm 1986;314:138). Hemorrhage into plaque causes sudden occlusions

Epidemiology ⬆ ⬇

Increased incidence in Western countries although it has decreased in last 25 yr, half due to decrease in risk factors and half due to medical rx (Nejm 1996;334:884) w improving post-MI survival (Nejm 1998;339:861)

Increased in diabetes, hypertension, obesity (Nejm 1990;322:882), inflammation as measured by sCRP and h/o acute infections (Nejm 2004;351:2599, 2611), air pollution (Nejm 2007;356:447), smokers perhaps via inflammation (CRP) and homocysteine levels (Ann IM 2003;138:891), pseudoxanthoma elasticum, myotonic dystrophy, alkaptonuria and ochronosis; homocystinuria/emia (Homocystinuria (Homocyst[e]inemia)) consumers of food w partially hydrogenated transfatty acids (Nejm 2006;354:1601); hyperlipidemias (Hyperlipidemias) especially LDL elevations often associated w apolipoprotein (epsilon) E4 allele (Jama 1994;272:1666), and w elevated lipoprotein (alpha.gif) (Jama 1996;276:544); sleep disorders (Am J Med 2000;108:396); adults who were low-birth-weight children to age 2+ yr (Nejm 2005;353:1802, 1848).

Weak (ACP J Club 1998;129(2):50) or no association w triglyceride elevations alone, although they are markers for other risk factors (Nejm 1993;328:1220)

Decreased in moderate (7-20 drinks/wk) alcohol drinkers (Jama 1999;282:239; Nejm 1997;337:1705, Ann IM 1997;126:372, Nejm 1995;332:1245; 1993;329:1829), via increased TPA as well as HDL (Jama 1994;272:929) and flavins in red wine which appears to decr cancer mortality in addition (Ann IM 2000;133:411); in runners (Nejm 1980;303:1159), and otherwise regularly exercising men (Nejm 1998;338:94, 1993;328:533, 538, 574; 1993;329:1829) and women (Jama 2001;285:1447) via protective elevations of HDL cholesterol component; with high fiber diets (20+ gm qd) (Jama 1999;281:1995) like those high in fruits and vegetables (Ann IM 2001;134:1106); with increased fish intake of omega-3 or N-3 fatty acids (see Atherosclerosis); Mediterranean diet (Nejm 2003;348:2599)

Signs and Symptoms ⬆ ⬇

Sx:Claudication, angina, MI, sudden death, TIA/CVA, abdominal angina

Si:Renal hypertension; bruits, absent peripheral pulses; CVAs; arcus senilis in Caucasians age <50 yr (Nejm 1974;291:1323) is a risk factor independent even of cholesterol levels (Am J Publ Hlth 1990;80:1200); retinal fundal vessel plaques, arterial narrowing correlates w MI risk in women but not men (Jama 2002;287:1153)

Complications ⬆ ⬇

All of above

Lab and Xray ⬆ ⬇

Lab:

Chem:Cholesterol (Hypercholesterolemia) Apolipoprotein A2 (Nejm 2000;343:1149) (components of HDL) may be better predictors

Hem: sCRP levels >1.55 mg/L, of doubtful utility (Nejm 2004;350:1450) but may ID candidates for primary statin preventive rx (Nejm 2008;359:2195, 2280)

Path:Lipid in foam macrophages and smooth muscle; free cholesterol crystals between intima and media

Xray:Electron beam CT screening of unproven value (Nejm 1998;339:1964, 1972, 2014, 2018)

Treatment ⬆

Rx:

Prevent (Ann IM 2005;142:393)

  • Stopping smoking
  • Cholesterol LDL elevation rx (Klinefelter's Syndrome) to get <100 mg % (Nejm 1997;336:153, Circ 1994;89:1329) at least in pts w ASHD; helps both by decreasing plaques and by preventing coronary artery spasm (Nejm 1995;332:481, 488); low saturated rather than low total fat diet (Jama 2002;288:2519) incr fruits vegetables and whole grains; Indo-Mediterranean (Lancet 2003;360:1455, Nejm 2003;348:2599)
  • Cholesterol HDL depression; try to get over 60, at least over 40 w niacin (Nejm 2009;361:2113, 2180)
  • Alcohol at 2-3 drinks qd decreases mortality by 25% (Am J Publ Hlth 1993;83:805)
  • Omega-3 or N-3 fatty acids, as qd capsule (Lancet 1999;354:447) or 1 fatty fish meal/day-mo decreases incidence of cardiac arrest by up to 50% (Jama 2002;287:1815; ACP J Club 2000;132:6; Nejm 1997;336:1046), which also decr stroke risk by 50% (Jama 2001;285:304) and sudden death (Nejm 2002;346:1113); counteracted by mercury content of fish (Nejm 2002;347:1747) but risk/benefit ratio worth it (Jama 2006;296:1885)
  • Carbohydrate reduction and replacement with vegetable fats and protein (Nejm 2006;355:1991)
  • Exercise (Jama 2001;285:1447; 1998;279:440) moderate (2-3 mph) walking 1-2 hr/wk; total more important than intensity; increases fibrinolysis (Nejm 1980;302:987)
  • Rx of diabetes and hypertension
  • ASA 80-320 mg (Nejm 2005;352:1293 [women]; USPSTF in Ann IM 2002;136:157; ACP J Club 2001;135:88) po qd decr MIs (men) and CVAs (women) especially if CRP chronically elevated (Nejm 1996;336:973, 1014); primary prevention in diabetics (Jama 2008;300:2134); effect is counteracted by ibuprofen but not acetaminophen or diclofenac (Voltaren) (Med Let 2004;46:61)
  • ACE inhibitors in pts w diabetes or vascular disease and other risk factors decr MI, sudden death, and CVAs, even if normal EF, NNT-4 = 14 (Nejm 2000;342:454)
  • No help from:
    • Folic acid and/or vit B6, and/or vit B12 and may incr cancer and mortality (Jama 2010;303:2486; 2009;302:2119, 2152; 2008;299:2027; 300:795)
    • sCRP (Jama 20098;302:49,92; Ann IM 2006;145:35, 70), no point in reduction strategies
    • Vit E, antioxidant; DBCTs show deleterious, all cause mortality and CHF effect (Ann IM 2005;142:37; Jama 2005;294:52; 293:1338; Nejm 2001;345:1583; 2000;342:154; Jama 2002;288:2432). No stroke reduction either (Ann IM 1999;13:963)
    • EDTA chelation of various heavy metals (Med Let 1994;36:48)
    • beta.gif-carotene (Nejm 1996;334:1145, 1150, 1189, Jama 1996;275:693, 699—ERT) (Estrogen Replacement Therapy) of disease, various tertiary maneuvers to fix damage especially surgery, eg, angioplasty/CABG, femoral-popliteal bypass, etc; plus dietary measures, eg, "Mediterranean diet" reduces subsequent mortality from 5% to 1% (Arch IM 1998;158:1181; Lancet 1994;343:1454) and can reverse ASHD vessel diameter narrowing (Jama 1998;280:2001; Ann IM 1994;121:348)