Clinical Pearls from the 10th Annual SMAASH Carolinas Georgia Chapter Meeting June 30July 2, 2006 My

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Clinical Pearls from the 10th Annual SMA-ASH
Carolinas Georgia ChapterMeetingJune 30-July 2,
2006Myrtle Beach, SC
Jan Basile, MDDirectorPrimary Care Service
LineRalph H. Johnson VA Medical CenterProfessor
of MedicineMedical University of South
CarolinaCharleston, SC
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What we learned the 1st day

• AAs have an earlier onset and more severe stage
  of hypertension than their caucasian
  counterparts. Males, regardless of ethnicity,
  have poorer BP control rates than females.
• An inflammatory risk factor is causative of
  atherosclerosis while an inflammatory risk marker
  is the result of atherosclerosis.
• Only the highest quintile of hsCRP discriminates
  the risk of CVD making it a less worthy risk
  marker for clinical use in the general
  population.
• Cystatin C is a better marker of renal risk for
  CVD than eGFR which is a better marker than serum
  creatinine.

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What we learned the 1st day (Cont)

• Ambulatory BP monitoring provides additional
  information on CV risk on top of that gained from
  clinic BP.
• Home BP measurement improves medication adherence
  and BP control and has important prognostic
  accuracy over clinic BP readings (masked
  hypertension (OO/IO-).
• The goal of clinical guidelines is to change
  practice styles, reduce inappropriate and
  unnecessary care, and cut costs.
• If we overcome therapeutic inertia (the failure
  to either increase the dose of an
  antihypertensive agent or of antihypertensive
  agents), we can improve on BP control rates of lt
  140 mm Hg/90 mm Hg from 45 to 78.

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What we learned the 1st day (Cont)

• If you could only do 1 lifestyle intervention to
  reduce BP, it would be to use the DASH Diet
  (-5.5/3 mm Hg) with the greatest effect in those
  with the highest BP and in African Americans with
  hypertension.
• Chronotherapeutics is a strategy that is
  currently unproven for outcome improvement but
  represents a strategy that could potentially
  affect CV disease outcome.

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What we learned the 2nd day

• Resistant hypertension is defined as the failure
  to control BP lt 140/90 mm Hg on full doses of 3
  antihypertensive agents, one of which is a
  thiazide-type diuretic.
• The use of clonidine and BB together can be a
  cause of drug-induced hypertension.
• Alcohol (3 or more drinks per day) is responsible
  worldwide for at least 16 of all hypertension
  seen.

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What we learned the 2nd day (Cont)

• Over 6 years, hypertension is more likely to
  develop in those without previous hypertension
  who drink 3 or more compared to 2 drinks per day.
• Heavy drinking is 1 of 6 leading causes of
  uncontrolled hypertension listed in JNC 7.
• 2 drinks per day in men and 1 drink per day in
  women (12 oz beer, 5 ounces wine, 1.5 ounces
  liquor) is cardioprotective, even in those with
  hypertension. The key to achieve this
  cardioprotective benefit is to limit alcohol use
  to this amount.
• CDT (level gt 2.6) is a more specific than
  sensitive marker of alcohol excess (4 or more
  drinks per day) for at least 2 weeks and can be
  combined with GGT to measure likelihood of
  alcohol excess in a primary care practice.

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What we learned the 2nd day (Cont)

• Primary Aldosteronism, previously felt to be an
  unlikely cause of secondary hypertension, now is
  more commonly observed depending on the severity
  of hypertension (8 Stage 2 to 13 of Stage 3)
  and about 20 of those with resistant
  hypertension.
• OSA is prevalent in about 23 of men a 9 in
  women and increases to about 35 of those with
  hypertension, 65 of obese men, and 96 of men
  and 65 of women with resistant hypertension.
  There is a direct relationship between the
  severity of the OSA and plasma and urinary
  aldosterone levels in those with resistant
  hypertension.

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What we learned the 2nd day (Cont)

• As monotherapy, BBs appear to be most effective
  in white males lt 60 years of age whereas
  thiazide-type diuretics were no more effective
  than placebo in the same VA population. BBs
  appear to be less effective in the elderly as
  single-agent therapy unless that hypertensive
  individual has a compelling indication for their
  use (post MI, type 2 AODM). They can be used as a
  second or third step agents in a variety of
  situations including older hypertensives, after a
  diuretic in those with ISH, in those with LVH,
  and in those with diabetes with a HR gt84.

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What we learned the 2nd day (Cont)

• Differences seen in the HOPE, EUROPA, AND PEACE
  Trials can probably be explained by differences
  in background risk which may reflect differences
  in RAS excitation rather than specific
  differences in the ACE inhibitor used. That said,
  ramipril 10 mg or perindopril 8 mg once-a-day is
  evidence-based in high risk individuals some of
  whom have hypertension.

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What we learned the 2nd day (Cont)

• Differences in the ARBs exist in terms of
  clinical pharmacology, cytochrome P450
  interaction, elimination by the liver, effects on
  afib, LVH, effects on uric acid, and ppar gamma
  the use of these drugs however should be specific
  at the dose and frequency of dose studied showing
  a benefit in lowering BP (all), reduce stroke
  risk (losartan), reduce HF morbidity (valsartan
  and candesartan) and HF mortality (candsesartan)
  and slowing progression to ESRD (losartan and
  irbesartan).

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What we learned the 2nd day (Cont)

• In essential hypertensives, the vasodilatory
  peptide ang-(1-7) is decreased compared to normal
  controls.
• The vasodilatory effects of the 7 amino-acid
  peptide ang-(1-7) is up regulated in 2 rat
  hypertension models with increased RAS activity
  by a low salt diet.
• ACE inhibitors and ARBs act by blocking the
  effects of angiotensin II allowing the increased
  production of ACE2 and the further increased
  downstream production of ang-(1-7).

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What we learned the 3rd day

• In the type 2 diabetic, achieving a further
  reduction of 10/5 mm Hg in BP (final level 144/82
  mm Hg versus 154/87 mm Hg) translates into a 24
  reduction in any diabetic complication, 44
  greater reduction in stokes, and 50 reduction in
  heart failure.
• The HOT trial in 1501 type 2 diabetics showed
  achieving a diastolic goal of lt 80 mm Hg improves
  CV outcome compared to lt 90 mm Hg.
• Until the results of the Action to Control
  Cardiovascular Complications in Diabetes (ACCORD)
  trial is completed in the year 2009 comparing a
  systolic BP goal of lt 120 mm Hg vs lt 140 mm Hg,
  the BP goal in a type 2 diabetic will remain at
  lt130/80 mm Hg.

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What we learned the 3rd day (Cont)

• For patients who have heart failure with
  preserved ejection fraction, the control of BP
  and other atherosclerotic risk factors is more
  imperative than the use of a specific class of BP
  lowering agent(s).
• Valsartan (bid) and Candesartan (qd) are both
  indicated in those with heart failure intolerant
  of an Ace Inhibitor (VAL-HeFT, CHARM-Alternative)
  while only Candesartan is FDA approved in those
  with heart failure who are on an ACE inhibitor
  and BB (CHARM-Added).

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What we learned the 3rd day (Cont)

• The presence of microalbuminuria (part of the WHO
  criteria for the metabolic syndrome MS but not
  part of the NCEP III criteria) is more prevalent
  in the AA male. Its presence increases the
  prevalence of the MS from 16 to 25.
• Lifestyle Modification (weight loss and exercise)
  is the most evidence-based way of preventing the
  onset of type 2 diabetes although smoking
  cessation, metformin, troglitazone, ACE inhibitor
  and ARB therapy, statin use, and bariatric
  surgery are also effective in preventing new
  onset diabetes. Whether these therapies will
  improve the outcome in those with the metabolic
  syndrome is untested.

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What we learned the 3rd day (Cont)

• The LDL goal should be lt 100 mg/dl in those with
  vascular disease and lt 70 mg/dl as a therapeutic
  option in the highest risk individuals including
  those with known CAD and hypertension.
• While the Framingham Risk score can be used to
  estimate the need for statin-based therapy and
  the appropriate LDL level to achieve, trials such
  as ASCOT-LLA enrolling patients all of whom had
  hypertension and 3 or more risk factors found
  benefit in reducing cardiovascular and
  stroke-related morbidity and mortality using
  statin-based therapy. We can no longer allow our
  patients with hypertension to escape our radar
  screen for using statin-based therapy for outcome
  improvement. Using the inclusion criteria from
  the ASCOT-LLA trial will help us better recognize
  who these patients are.

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What we learned the 3rd day (Cont)

• The key to improving cardiovascular outcome in
  those with hypertension is to reduce BP to goal
  while using the appropriate cocktail of therapy
  especially when there is a compelling indication
  for such use.
• Clinicians are encouraged to join our ASH
  Carolinas Georgia Chapter whose mission is to
  improve vascular health in our region.