ot;width=device-width,initial-scale=1.0,minimum-scale=1.0,maximum-scale=1.0" : "width=1100"' name='viewport'/> 2020 Update in Clinical Endocrinology: Dyslipidemia AACE 2020 guidelines: Definition, Epidemiology, Etiology, Diagnosis, General Measures.

Tuesday, October 13, 2020

Dyslipidemia AACE 2020 guidelines: Definition, Epidemiology, Etiology, Diagnosis, General Measures.

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DEFINITION

  • The term dyslipidemia is a hotchpotch. Certain features of serum lipids and lipoprotein profile are associated to aterosclerosis (AS), which is a disease, and to triglyceride-related outcomes. Serum cholesterol in LDL, VLDL, VLDL remnants, and Lp(a) lipoproteins are risk factors for AS. triglycerides in VLDL and chylomicrons are risk factors for TG related events (see below).

EPIDEMIOLOGY

  • About 30, 25 and 20% of US citicens have LDL, TG and Lp(a) values above which experts consider risk threshold. Important to know that thresholds are arbitrary. 
  • Prevalence of specific syndromes of dyslipidemia are listed in etiology.

ETIOLOGY

    • Primary hyperlipidemias:
      • Hypercholesterolemia (HC).
        • As said, 30% of US adults have cholesterol levels above threshold. Be careful, it's not a disease, it's just defined according to CVD risk. 
        • Familial hypercholesterolemia. Mutations affecting LDL receptor function. Codominant:
          • Heterozygous: 1/250-500. LDL >190 mg/dL in adults (160 in children) and CVD.
          • Homozygous: 1/1-4 million. Extreme CVD risk, LDL >500 mg/dL.
      • Hypertriglyceridemia (HT). The same, defined if fasting Tg >=150 mg/dL (25% of US adults) and severe if >=500.
      • Both HC+HT: three main possibilities:
        •  HC and HT with no known specific cause. By far the most common, generally mild, treat both according to guideline. 
        • Familial combined hyperlipidemia (FCH). 1-3% of US adults. Defined as ↑C or Tg in >=2 family members and premature ASCVD. 
        • Dysbetalipoproteinemia. ↑VLDL and chilomicron remnants, ↑Tg and C and premature ASCVD. Recessive, usually no family members seen.
      • Elevated Lp(a). ↑CV disease. 20% of US adults. 
      • Other, less common:
        • Familial Chylomicronemia syndrome. 
        • Hypoalphalipoproteinemia.
        • Beta-sitosterolemia.
        • Lisosomal acid lipase deficiency. 
    • Secondary hyperlipidemias: quite a lot. The document says the most frequent in developed countries are sedentary lifestyle and carbs in diet, but without references. That means that either they get their knowledge directly from God or they make it up.
      • Lifestyle: sedentary LS, alcohol, saturated fat, carbohydrates and sugar. In the document there's also "malnutrition" but I think that's a different context.
      • Diseases: 
        • Obesity - metabolic syndrome
        • Uncontrolled hyperglycemia
        • Pregnancy
        • Hypothyroidism
        • CKD stage >=3
        • Nephrotic syndrome
        • Cholestasis
        • Paraproteinemia
        • Lipodystrophy
        • Rheumatologic diseases like SLE or RA 
      • Drugs:
        • Sex hormones: estrogens, gestagens, androgens, SARM
        • Antihypertensive: thiazides, beta-blockers
        • Immune drugs: IFN, cyclosporine, mTOR-K inhibitors
        • Chemotherapy: taxols, cyclophosphamide, L-asparaginase
        • Glucocorticoids
        • Retinoids
        • Bile acid sequestrants

    DIAGNOSIS

    • Percent undiagnosed and time from onset to diagnosis: already stated in epidemiology. Most people at risk are not taking drugs, which could have terrible consequences for big pharma CEOs.
    • Diagnostic workup:
      • Perform serum lipids in:
        • people included in secondary causes
        • personal or family history of premature ASCVD, corneal arcus, tendon xantomas or xanthelasmas (cholesterol)
        • pancreatitis, lipemia retinalis or eruptive xanthomas (Tg)
      • Physical exam: include BMI, BP, pulses, ABI, waist circumference, xanthelasmas, eruptive and tendon xanthomas, corneal arcus, lipemia retinalis. 
      • Laboratory:
        • Basic: cholesterol, LDL, HDL, TG, biochemistry with A1c, uric acid and TSH. 
        • Optional: ApoB, LDL particles, Lp(a), hs-PCR. 
      • ECG: resting or treadmill, chemical or nuclear stress
      • Image:
        • Coronary Artery Calcium (CAC): recommended
        • Carotid intima-media thickness, used for years, not predictive of CVD. 
      • Risk Calculators:
        • Framingham
        • MESA (Multiethnic Study of Atherosclerosis) incorporating CAC.
        • Reynolds
        • UKPDS
        • ACC/AHA
    • ASCVD risk categories and goals: Now we're leaving science and enter a world of fantasy. The panel has established 5 categories of risk, from low to extreme, with corresponding LDL goals. We're sure that, if you changed panel members, or even same members joined another day, categories and goals would be different, but that's what we've got. 
      • Goals (specific goals are different for each category, see below):
        • LDL colesterol. It is the main goal because many RCT proved that the lower level the lower CVD events, mostly with statins, but also with statin+ezetimibe and PCSK9i.
        • Non HDL colesterol. Usually the goal is 25-30 mg/dL higher than LDL. It includes not only LDL but also all other atherogenic particles: VLDL, IDL, Qm and Lp(a).
        • ApoB. Important in metabolic syndrome, where LDL levels may be OK but small dense particles are disclosed by measuring ↑ApoB. It is the sum of B100, that is included in all atherogenic particles (VLDL, IDL, LDL) and B48.
        • TG. Values >150 are high and >500 mg/dL extremely high. Its reduction lowers CVD in reduce-it with EPA and in subgroup analysis with fibrates if low HDL. 
        • HDL. Low levels are associated to CVD but pharmacologic raising does not ↓CVD. Recommendation is non-drug-raising and then use statins to lower LDL.
      • Categories:
        • Extreme risk: LDL-C <55, non-HDL-C <80, ApoB <70, TG <150:
          • Proggressive ASCVD including unstable angina
          • Established clinical ASCVD + DM or CKD >=3 or HeFH
          • Premature (<55a♂ <65♀) ASCVD
        • Very high risk: LDL-C <70, non-HDL-C <100, ApoB <80, TG <150
          • Established clinical ASCVD
          • 10-y risk >=20% 
          • DM + other RF
          • CKD >=3 + albuminuria
          • HeFH
        • High risk: LDL-C <100, non-HDL-C <130, ApoB <90, TG <150
          • 10-y risk 10-20% and >= 2 RF
          • DM with no other RF
          • CKD >=3 with no other RF
        • Intermediate risk: LDL-C <100, non-HDL-C <130, ApoB <90, TG <150. Yes, they're the same as in high risk. Maybe that day they were in a hurry for some reason to finish the meeting.
          • <2 RF + 10-y risk <10%
        • Low riks: LDL-C <130, non-HDL-C <160, TG <150
          • No RF

    MANAGEMENT

    • General measures:
      • Diet: no consensus no single strategy:
        • DASH and mediterranean diet satisfy the general recommendations: fruits and vegetables, whole grains, legumes and soluble fibre, avoid processed food and reduce total calories.
        • With no evidence whatsoever, the panel favor diets with total fat 25-35% of calories  (i.e. DASH > mediterranean), Diets with <25% fat ↑TG and ↓HDL, although those with 10% fat (ineadible!) ↓CV events. 
        • Soluble fiber ↓LDL, insoluble fiber ↓CVD.
      • Exercise:
        • ↓obesity, waist, glycemia, HT, dyslipidemia
        • ↓Tg and hsPCR, ↑HDL, no clear effect on LDL. 
        • >150 min moderate aerobic + weights and resistance 
      • Sleep hygiene:
        • 6-8 h sleep ↓CVRF: HT, glycemia, lipidemia, inflammation. 
        • OSA ↑ CVD
      • Mental issues: depression, schizophrenia, bipolar disorder, anxiety andpost-traumatic syndrome ↑CV risk, but no evidence that any intervention prevents it. 
      • Alcohol: 
        • some meta-analyses associate OH and lower CV events, but its consumption is obviously not recommended
        • Excess OH ↑TG and HDL, but not the protective subfraction, ↑HT, cardiomyopathy and atrial fibrillation.
      • Stop smoking 
        • Smoking ↑CV risk x3, stopping ↓risk very early, 1st year, and at year 5 risk is similar to non-smokers. 
    That's enough for today, about 1000 words = 10 min. Next post, drug therapy,