HTN
Note: If you copy and paste this into your document, the below tables & boxes are best viewed with Rt & Lft margins of 0.5”

See PPT presentation pp 288-292 of DIDACTIC MANUAL as this was the main area covered during the didactic LECTURE:

Interesting Note: Family Physicians will Dx & Tx HTN 2x more than any other Dx!!!

1st Line Drugs (Various goals:  TPR,  CO,  fluid) “Start low & go slow”
No comorbid dz /

Diuretic or -Blocker (proven to  mortality + cheaper)

Heart failure (CHF) / ACE-I or ARB (Losartan)

Diuretics

Carvedilol ( block): ’s sympathetic stimulated remodeling
MI / -Blocker (non-ISA) proven to  mortality
ACE-I (w/ systolic dysfncn= ’d ejection fraction) proven to  mortality
CCB: diltiazem or verapamil (nonDHPs)
DM (1 & 2) w/ proteinuria / ACE-I (proven to  vascular & renal dz)
CCB (NOT nifedipine due to vasodilation!)
DM 2 /

Low-dose diuretics

ISH (older persons) / Diuretics (preferred)

Long-acting dihydropyridine CCB (-dipine)

Angina / -Blocker

CCB

Atrial tach & fib / -Blocker

NONdihydropyridine CCB

Cyclosporine-induced HTN /

CCB

Dyslipidemia / -Blocker
Prostatism (BPH) / -Blocker (may  urinary incontinence in women)
Renal Insufficiency / ACE-I (caution in renovascular HTN & creatinine > 3mg/dL)
Essential tremor / NONcardioselective -Blocker
Hyperthyroidism / -Blocker
Migraine / NONcardioselective -Blocker

NONdihydropyridine CCB

Osteoporosis /

Thiazides (’s Ca excretion)

Perioperative HTN / -Blocker

Remember: PREGNANCY is NOT the PLACE for ACE!!! (Rated category X due to teratogenicity); Don’t use ARB’s either!!

See Didactic Manual pg 290, slide 16 & 17 for drugs of choice in pregnancy (Methyldopa) & slide 18 for DM pharmacotherapy

Comments related to the slides on pg 291 & 292:

  • Dyslipidemia slide: 10 lbs wt  10mm Hg BP
  • Tx of sleep apnea with CPAP (Continuous Positive Airway Pressure) machine may improve HTN, too!
  • On the ACE-I chart (p 291, slides 22&23), while certain drugs do not show FDA approval for CHF, the “class effect” should still provide benefit for CHF
  • On the -blocker chart (slides 24&25), notice that the high lipid solubility of propranolol should be avoided in the elderly due to its ability to cross the BBB &  confusion; wt gain has been assoc’d w/ -blockers but this may be due to the fact that pts are advised to take them with food; sotalol is only indicated for arrhythmias
  • CCB chart (slide 26), the long t½ of amlodipine (Norvasc) makes for slower onset & therefore better compliance among pts; nifedipine  vasodilation  rebound  in HR
  • 60 yo is actually a better age than 50 for Dr. Sneed’s Rule of 50
  • Take note of the side effects of different groups of anti-HTN meds on p 293 of the Didactic Manual

Highlights from the READINGS:

Marks, JB. Tx’ing HTN in DM: Data & Perspectives. Clinical Diabetes, 1999; 17(4): 148-153.

Goal for Diabetics: <130/85mm Hg, NOT likely to be achieved by monotherapy in most pts, & therefore  combos needed

ISH=Isolated Systolic Hypertension: sBP>160mm Hg & dBP<90mm Hg

’d Susceptibility Hypothesis: poor glycemic control may  the risk for CV events in pts on CCBs (not proven)

Major Trials Discussed & Their Pertinent Findings:

  • SHEP=Systolic Hypertension in the Elderly Program: study assessed the effect of low dose diuretic-based anti-HTN tx on CV event rates in older DM 2 & non-DM pts w/ ISH; showed avg after tx of 145/70 &  in mortality.
  • Syst-Eur=Systolic HTN in Europe study: showed that anti-HTN tx ’s risk of CV complications in elderly pts w/ isolated HTN (avg of 153/78 for tx’d grp vs 162/82 for un); also showed benefit of ’ing sBP in the diabetic grp
  • HOT trial=Hypertension Optimal Tx trial: pts 1st started on a CCB & then 41% of pts required addition of an ACEI & 28% a -blocker to achieve BP target; results showed benefit of ’ing BP in DM pts & ’d CV moratlity overall.
  • UKPDS=United Kingdom Prospective Diabetes Study: showed even small ’s in BP have big impact on CV risk – the lower, the better; 34%  in 2-step progression of retinopathy & a 47%  in risk of decline in visual acuity
  • EPESE=Established Populations for Epidemiologic Studies of the Elderly: showed that use of CCB short-acting nifedipine was assoc’d w/ ’d survival
  • MIDAS=Multicenter Isradipine Diuretic Atherosclerosis Study ’d angina & CV events in CCB vs diuretic grp
  • FACET=Fosinopril Versus Amlodipine CV Events Randomized Trial: initial tx of fosinopril vs amlodipine; fosinopril grp after 3.5yrs had a 50% lower incidence of major CV events. Either due to good effect of ACEIs or bad effect of CCBs. The former explanation is more likely. Study was criticized for several reasons, especially  placebo grp
  • ABCD=Appropriate BP Control in Diabetes trial: showed ’d incidence of MI w/ CCB grp. However, study was not designed to test the effect of 1 drug vs the other on CV outcomes;  placebo grp was used!
  • MDNS=Melbourne Diabetic Nephropathy Study:  difference in rate of decline of GFR btwn ACEI vs long-acting CCB grps

Microvascular Benefits of BP control:

  • ’s albumin excretion rate by 50% & ’s rate of decline in GFR
  • ’s progression of microalbuminuria & rate of  in renal fncn regardless of drug choice
  • Renal benefits even in “normotensive” DM pts
  • ’s dvlpmt & progression of retinopathy

Ideal anti-HTN Drug for DM?:

  • Those that improve (or don’t worsen) insulin resistance, dyslipidemia, glycemic control, &/or nephropathy
  • Drugs that don’t worsen DM Sx of sexual dysfncn, hypoglycemia, & orthostatic hypotension
  • Low dose diuretics have been shown effective in DM pts w/o significant effect on glycemic control or lipid profiles
  • While -blockers cause concerns of hypoglycemia, adverse effects on glucose & lipid control, & CV risk, UKPDS presents evidence to the contrary: when compared to ACEI captopril, -blocker atenolol showed  different incidence of MI, stroke, CHF, or hypoglycemia
  • Overall, based on current data, a good approach is 1st ACE-I, then dihydropyridine CCB, then a low-dose diuretic and/or -blocker.

Lancet 1999; 354: 1744-5, 1751-6.

  • Pts taking “conventional” drugs (-blockers or diuretics) were no more or less likely to die from CV dz than were those who took ACEIs or CCB.

Circulation 1999; 100: 2312-8.

  • ACEIs less effective for CHF @ LOW doses (usu given by docs b/c of fear of hypotension)

Deedwania, PC. HTN & Diabetes. Arch Intern Med. 2000; 160: 1585-1594.

  • CV dz is  2-4x more common in diabetic pts than in nondiabetic pts & accounts for  50% of all DM-related deaths
  • HTN + DM 2 renders a diabetic 2x as likely to experience CV events as a nondiabetic person
  • Whereas the complications of DM 1 are mostly microvascular, pts w/ DM 2 are more susceptible to acceleration of atherosclerosis
  • Coexistence of DM 2 & HTN may be related to endothelial dysfncn
  • Diabetic nephropathy is the most common cause of End-Stage Renal Dz (ESRD) in the US
  • 65% of pts w/ diabetic nephropathy have DM 2 & HTN is a major risk factor for its dvlpmt
  • The nl 24-hr urinary protein excretion rate ranges from 50-150 mg/dL
  • The nl Urinary Albumin Excretion Rate is  8mg (range, 0-30mg); the UAER is a hallmark of renal dz
  • In pts w/ DM 2 & proteinuria, GFR ’s @ an annual rate of 4-12 mL/min
  • On avg, ACE-Is  proteinuria in diabetic pts even if bld pressure is not ’d
  • ’d efferent arteriolar resistance, mediated by excessive responsiveness to angiotensin 2, leads to ’d glomerular capillary pressure, accelerated decline in renal fncn, & ’d glomerulosclerosis; ACE-Is protect the kidneys against this effect & improve endothelial fncn
  • In the kidney, virtually all angiotensin II generation is renin dependent, but @ least 40% of angiotensin I is converted to angiotensin II by pathways other than ACE, presumably by a chymase. Consequently ARBs may produce ’s in renal plasma flow that are > than those attained w/ ACE-inhibition.
  • Diabetes is estimated to affect @ least 5% of the population of industrialized countries, w/ 90% of those w/ diabetes having type 2 DM.
  • Since 1987, the incidence & prevalence of ESRD have more than doubled, and deaths from ESRD also are ’ing

Frank or overt albuminuria = UAER  300mg/dL; UAER of 30 mg/dL is also abnl & is predictive of eventual dvlpmt of proteinuria, diabetic nephropathy, & ’d risk of micro- & macro-vascular complications.

Microalbuminuria = UAER of 30-300 mg/dL.; sustained microalbuminuria is an indicator of diabetic nephropathy & the single strongest predictor of the dvlpmt of coronary events; once present it progresses to proeteinuria in anywhere from 22-50% of pts over 5-10yrs.