10-1 CARDIOVASCULAR PROTECTION AND BLOOD PRESSURE REDUCTION: A Meta-Analysis
      On average, all antihypertensive drugs have similar long-term efficacy and safety in providing cardiovascular protection.
      Compared with diuretics and beta-blockers, calcium channel blockers might protect more against stroke and less against myocardial infarction. This results in an overall cardiovascular benefit similar to that of old classes of antihypertension drugs.

10-2 EXTRACRANIAL CAROTID STENOSIS
Symptomatic CS
      All should receive antiplatelet medication: aspirin, clopidogrel (Plavex), or the combination of aspirin and dipyridamole. Anticoagulant therapy is not routinely recommended.
      Endarterectomy: Indicated for patients with 70% to 99% stenosis who are good candidates for surgery and have had symptoms within the past 2 years. For those with 50% to 69% stenosis decision for surgery should be made on the clinical features that influence risk of stroke vs the risks of surgery.

Asymptomatic CS:
      Surgery should be individualized and considered for those under age 80 with stenosis > 60% if an experienced surgeon is available. Presence or absence of coexisting conditions, life expectancy, and patient preferences should be considered.

10-3 TRANSIENT MONOCULAR BLINDNESS ASSOCIATED WITH CAROTID ARTERY STENOSIS.
      As compared with hemispheric TIA, TMB associated with internal carotid stenosis carries a better prognosis with respect to subsequent stroke. Endarterectomy may improve prognosis in the group with other risk factors for stroke.
      Practical point: This does have some clinical application to primary care. Patients with TMB may be informed more accurately about prognosis. Clinician and patient may more easily reach agreement about treatment.

10-4 GAIN IN BONE MINERAL MASS IN PREPUBERTAL GIRLS 3-5 YEARS AFTER DISCONTINUATION OF CALCIUM SUPPLEMENTATION.
      Calcium supplementation during childhood and adolescence increases bone mass. Peak bone mass at the end of the prepubertal period is a major determinant of risk of osteoporotic fractures in later life.
      Practical point: Primary care clinicians should make sure their adolescent girl patients receive adequate intake of calcium and vitamin D. Supplementation is often needed.

10-5 RAMIPRIL AND THE DEVELOPMENT OF DIABETES
      Ramipril, an ACE inhibitor, reduced risk of developing diabetes in high risk individuals. The number need to treat to benefit one patient is high

10-7 NARRATIVE MEDICINE
      Narrative competence is the competence that human beings use to absorb, interpret, and respond to stories others tell. Everyone has a story to tell. Along with scientific ability, physicians need the ability to listen to the narratives of the patient, grasp and honor their meaning, and be moved to act on the patient's behalf.

10-8 "I WISH THINGS WERE DIFFERENT": EXPRESSING WISHES IN RESPONSE TO LOSS, FUTILITY, AND UNREALISTIC HOPES
      "When the emotion is unrealistic hope, loss, futility, or grief that seems overwhelming or otherwise is very difficult to address, physicians should consider joining with the patient and family in the expression of a wish that their circumstances were different."
      In these challenging situations physicians may attempt to respond empathetically by stating "I'm sorry". This well intentioned response, although frequently appropriate, may be misinterpreted and misdirected.
      Practical point: Primary care clinicians will develop their own individual approaches when encountering difficult emotional situations. This suggestion is a worth-while approach.

10-9 OBSERVATIONAL STUDY OF EFFECT OF PATIENT CENTEREDNESS AND POSITIVE APPROACH ON OUTCOMES OF GENERAL PRACTICE CONSULTATIONS.
      Patient-centered approach includes five components.

1. Communication and partnership with the doctor.
2. Personal relationship with the doctor.
3. Health promotion.
4. Positive approach to diagnosis and prognosis.
5. Interest in the effect of the illness on the patient's life.

10-10 PROGNOSTIC VALUE OF A NORMAL OR NONSPECIFIC ELECTROCARDIOGRAM IN ACUTE MYOCARDIAL INFARCTION
      In a large cohort of hospitalized patients with eventually established acute MI, those presenting with an initially normal or non-specific ECG had lower in-hospital mortality than those with initially diagnostic ECGs. However, absolute rates of mortality and complications were unexpectedly high.
      Practical point: Among patients presenting with suspected acute MI, some will be discharged home without a proper diagnosis. Although they are relatively few, the consequences may be disastrous. These patients should be rechecked the next day even though the clinician feels the risk of MI is small. It would be reasonable to routinely give these patients prophylactic aspirin and even low-dose beta-blockers before discharge home.

10-11 FAST DIAGNOSIS OF MYOCARDIAL INFARCTION
      A new test procedure now approved by the FDA simultaneously measures 3 cardiac markers: troponin I, creatine kinase-MB, and myoglobin. All are released by the damaged myocardium.
      It can be performed quickly at the bedside. It is very predictive in ruling out acute MI.

10-12 CONTRIBUTION OF INFLUENZA AND RESPIRATORY SYNCYTIAL VIRUS TO COMMUNITY CASES OF INFLUENZA-LIKE ILLNESS
      In individuals with influenza-like illness, there is a substantial potential for confusion between illness caused by RSV and IV. In this study about 20% of adults with flu-like symptoms were positive for respiratory syncytial virus. RSV is an important pathogen contributing to the burden of illness in the entire community in winter.
      Practical point: Watch for development of RSV vaccine for adults.

10-13 ELEVATED MIDLIFE BLOOD PRESSURE INCREASES RISK IN ELDERLY PERSONS: The Framingham Study
      Elevated BP during the midlife decades contributes to the risk of stroke in older age. Optimal prevention of late-life stroke will likely require control of midlife BP.
      Practical point: Hypertension should be controlled throughout life.

10-14 THE PROGNOSTIC VALUE OF B-TYPE NATRIURETIC PEPTIDE IN PATIENTS WITH ACUTE CORONARY SYNDROMES.
      A single measurement of BNP obtained within a few days of onset of ischemic symptoms provided powerful risk-stratification information across the entire spectrum of acute coronary syndromes.
      It predicted long term risk of death and non-fatal coronary events. The prognostic usefulness persisted after adjustment for the presence of HF and other important predictors of mortality.
      The authors suggest — B-type natriuretic peptide should be measured after an acute coronary syndrome in order to identify the risk of adverse outcomes. Treatment should be adjusted accordingly.
      Practical point: Primary care clinicians should keep this marker in mind. It has not yet reached frequent clinical application, but probably will in the near future.

10-15 ACUTE CORONARY SYNDROMES — BEYOND MYOCYTE NECROSIS
      Tests for neurohumoral activation (elevated brain natriuretic peptide) and inflammation (C reactive protein) may augment our ability to identify patients at risk of adverse events, and potentially help to reserve the most expensive and aggressive therapies to individuals at highest risk.
      Practical point: These two proteins will be increasingly used as risk markers.

10-16 CONGESTIVE HEART FAILURE TREATMENT
      The FDA has approved nesiritide (Natrecor), a preparation of human B-type natriuretic peptide, for intravenous treatment of acutely decompensated congestive heart failure (ADCHF).

10-17 EPIDEMIOLOGY AND DIAGNOSIS OF HELICOBACTER PYLORI INFECTION.
      A brief explanation of the pathophysiology of H pylori gastritis. Why do some develop duodenal ulcers and some develop gastric ulcers and cancer?

1. Searched for outcome trials that tested drugs to lower BP in normotensive and hypertensive patients. None had overt heart failure.
2. The quantitative review included nine trials -- over 62 000 patients.
3. All trials were randomized and controlled and published in peer reviewed journals. All assessed BP and cardiovascular events. All had a follow-up of over 2 years.

1. Compared with old drugs (diuretics and beta-blockers), calcium-channel blockers (CCBs) and ACE inhibitors (ACE) offered similar overall cardiovascular protection.
2. CCBs provided more reduction in risk of stroke, and less protection in risk of myocardial infarction.

1. "Results of outcome trials for antihypertensive drugs can be explained by blood pressure differences between groups."
2. All antihypertension drugs had similar long-term efficacy and safety.
3. "Our results show the desirability of lowering blood pressure as much as possible to achieve the greatest reduction in cardiovascular complications."
4. In older persons with isolated systolic hypertension, lowering systolic by 10 mm Hg reduced the risk of stroke by 38% and myocardial infarction 23%.
5. In patients with predominantly diastolic hypertension, corresponding benefits produced by a 5-6 mm Hg reduction in diastolic pressure were 38% and 16%.
6. "Blood pressure at entry explained little additional variance."
7. CCBs and ACE reduced fatal and non-fatal outcomes as effectively as diuretics or beta-blockers. Compared with the older drugs, they gave the same overall protection against cardiovascular complications. But, CCBs provided more reduction in risk of stroke and less reduction in risk of myocardial infarction.
8. "Our analysis does not indicate to what extent blood pressure should be lowered. This issue remains unsettled."
9. The BP gradients (fall in BP when treated) largely accounted for most differences in outcome. "These findings emphasize the desirability of blood pressure control."
10. "The hypothesis that ACE inhibitors might affect outcome beyond their blood pressure lowering effects remains unproved."

Symptomatic CS

All should receive antiplatelet medication ó aspirin, clopidogrel (Plavex), or the combination of aspirin and dipyridamole. Anticoagulant therapy is not routinely recommended.

Endarterectomy: Indicated for patients with 70% to 99% stenosis who are good candidates for surgery and have had symptoms within the past 2 years. For those with 50% to 69% stenosis, decision for surgery should be made on the clinical features that influence risk of stroke vs the risks of surgery.

Asymptomatic CS:

Surgery should be individualized and considered for those under age 80 with stenosis > 60% if an experienced surgeon is available. Presence or absence of coexisting conditions, life expectancy, and patient preferences should be considered.

1. The North American Symptomatic Carotid Endarterectomy Trial entered over 2800 patients. All had a history of TIA of non-disabling stroke associated with carotid stenosis.
2. Randomized to optimal medical treatment or optimal medical treatment plus endarterectomy.
3. The present study compared the risk of stroke in the subset of patients with TMB vs risk of stroke among patients presenting with hemispheric TIA.
4. Assessed the effect of endarterectomy vs medical treatment in patients with TMB and hemispheric TIA.

1. Medical treatment: 198 patients with TMB vs 417 with hemispheric TIA. Over 3 years, those with TMB had about half the risk of ischemic stroke as those with hemispheric TIA. (Relative risk = 0.53).
2. In the TMB patients, six factors were associated with increased risk: Age > 75; male sex; history of hemispheric TIA or stroke; history of intermittent claudication; carotid stenosis 80% to 94%; and absence of collateral circulation.
3.  

   Outcomes TMB	3-year risk of ipsilateral stroke		Absolute risk reduction	NNT
   No of risk factors	Medical	Surgical
   0 or 1 (low risk)	2%	4%	2% (harm)	50 (harm)
   2 (moderate risk)	12%	7%	5% (benefit )	20
   3 (high risk)	24%	10%	14% (benefit)	7

   (All patients had stenosis > 50%)

1. TMB is a common manifestation of internal carotid stenosis. It is a warning of impending stroke.
2. In this large series, the 3-year risk of ipsilateral stroke was less in those with TMB as compared with those with hemispheric TIA. The strokes which did occur were less disabling in patients with TMB than in those presenting with hemispheric TIA. (Perhaps because of better collateral circulation.)
3. Each small group of cells in the retina is more sensitive than a group of cells of similar size in the brain. Thus, a small platelet-fibrin embolus will more readily become clinically manifest in the retina. TMB may frequently result from small emboli that would be less likely to cause brain infarction.
4. In patients with TMB, the subset having high risk and stenosis of 80% to 94%, endarterectomy would be effective in preventing stroke over 3 years in one of every 7 patients undergoing surgery.

1. In an original controlled study, girls age 8 received Ca over 1 year. Their bone mass increased significantly more than those receiving placebo.
2. The present study measured bone variables in 116 girls who, at age 8, had received supplementation with milk-derived calcium phosphate 850 mg daily for 48 weeks, or placebo.
3. Remeasured bone density 4 years after discontinuation of calcium when subjects were age 12.

1. At 4 year follow-up the bone mineral mass was higher in 6 sites in the originally treated group vs the placebo group. The difference seemed to be due mainly to a greater gain in the size of bone without a significant change in bone mineral density.
2. Girls in the treated group gained more height as compared with the placebo group (+ 2 cm). The gain was mainly due to increase in height of the lumbar spine.

1. Increases in bone mineral mass resulting from calcium supplementation in young girls during 1 year were maintained for more than 3 years after discontinuation.
2. The observed increase was due to a greater increase in the size of bone.

1. Considered a subset of patients in the HOPE study1 (n > 5500). All had evidence of vascular disease. None had known diabetes. All were considered at high risk for development of diabetes.
2. All were over age 55 (mean = 66)
3. Randomized to: 1) ramipril up to 10 mg daily, or 2) placebo.
4. Follow-up = 4.5 years. Main outcome measure = self-reported diagnosis of diabetes.

1. Over 250 subjects developed diabetes during follow-up of 4.5 years
2. Of those taking ramipril 3.6% developed diabetes; vs 5.4% of those taking placebo. (Absolute difference = 1.8% NNT(4.5 years to benefit 1 person) = 55)

1. Ramipril reduced risk of a new diagnosis of diabetes among persons considered at high risk of diabetes.
2. Previous studies reported that patients treated with ramipril had lower fasting glucose and lower HbA1c levels han those taking placebo, or diuretics and beta-blockers.
3. Hypokalemia substantially impairs insulin secretory response. ACE inhibitors raise serum K by reducing aldosterone secretion, thereby lowering renal K excretion. (Aldosterone is the sodium retaining - potassium excreting hormone.)

1. Acquired individual data from 52 studies of first-degree relatives (mother, sister, daughter) of over 58 000 women who had BC. Compared data with over 101 000 matched controls without the disease.

1. Of the 58 000 women with BC, 7500 (13%) had a first degree relative who also had BC (12% had one affected relative; 1% had two or more).
2. Of the controls (no BC), 7% had first degree relatives with BC.
3. Risk of BC increased with the increasing numbers of affected family members. Compared with women with BC who had no affected relatives, risk ratio was 1.8 for those with one affected relative; 2.9 for those with 2, and 3.9 for those with three.
4. For women of any given age, the younger the relative was at diagnosis, the greater the risk.
5. For women up to age 50 with 0, 1, or 2 or more affected first degree relatives, risk was 1.7%; 3.7%, and 8.0% respectively.
6. For women up to age 80 with 1, or 2 affected first degree relatives risks were 7.8%; 13.3%; and 12.1%. Estimates of death from BC up to age 80 were 2.3%; 4.2%; and 7.6%.

1. The study confirms the well-established increased risk of BC among women with a family history of BC. "It also shows that most women with one or more affected first-degree relatives will never develop BC themselves."
2. "Most women who develop BC do not have an affected first-degree relative with the disease."
3. The study also confirmed that the risk of BC was greater in women having a first degree relative who developed BC at an early age (eg, < 35 vs >60); those who had more than one affected relative; those who had fewer children; those whose children were born at a later age (eg, > 30 vs < 20); those who had an early menopause; and those who used oral contraceptives within 10 years (vs those whose last use was 10 or more years ago).
4. Implications for counseling women:
         In more developed countries, lifetime probability of developing BC between ages 20 and 80 = 8% (one in 13) vs 13% ( one in 8) among those with one affected relative; and 21% (one in 5) with two affected relatives.
         Corresponding estimates of death from BC are 2.3%; 4.2% and 7.6%
         Most women with one or more relatives with BC are unlikely themselves to develop BC, and even less likely to die of it. In developed countries, of women with 2 or more affected first degree relatives, about 4 out of five would never acquire BC, and 12 of 13 would not die from the disease.
         For women with a first degree relative who develop BC, the onset of BC is likely to be after age 50.
         The majority of women who develop BC have no mother, sister, or daughter with the disease. Eight of nine women who develop BC have no first degree relatives with the disease.
   
   
5. Screening only women with family members with the disease would miss the large majority of BCs.

1. Observational study of over 850 consecutive patients used questionnaires to measure patient's perceptions of patient-centeredness. Identified components of patient's perceptions.
2. Assessed how these components related to outcomes.
3. Main outcome measures: patient's satisfaction, enablement, and burden of symptoms.

1. Analysis identified 5 distinct components of patient's perceptions that can be measured reliably:

   1)	Communication and partnership with the doctor:       The doctor was interested in my worries and what I thought the problem was; encouraged me to ask questions; was sympathetic; and carefully explained plan of treatment. We discussed and agreed together what the problem was and the plan of treatment.
   2)	Personal relationship with the doctor:       Knows me and my history and understands me and my emotional needs.
   3)	Health promotion:       Advised me about how to prevent and lower risk of future illness.
   4)	Positive approach to diagnosis and prognosis:       Was definite and explained clearly what the problem was; was positive about when the problem would settle.
   5)	Interest in the effect of the illness on the patient's life:       Was interested in the effect of the problem on my family and my personal life and on my everyday activities.

2. Satisfaction was related to communication, partnership, and a positive approach.
   Enablement was greater when the doctor had greater interest on the effect of the disorder on the patient's life, stressed health promotion, and adopted a positive approach.
   Symptom burden was reduced when the doctor's approach was positive.
   Referrals were fewer if the patients felt they had a personal relationship with the doctor.
3. Patients who felt the doctor approached the illness using these criteria were more satisfied with their care.

1. The National Registry of Myocardial Infarction compared risks of in-hospital death and life-threatening complications among patients with normal vs diagnostic initial ECGs.
2. Multicenter observational study enrolled over 390 000 patients (mean age = 68). All presented with a clinical history suggestive of acute MI, were hospitalized, and subsequently were considered to have had an acute MI on basis of the clinical presentation, CK-MB or other cardiac enzymes, an ECG compatible with acute MI, positive scintigraphic or autopsy evidence, or a discharge diagnosis of MI.
3. Determined numbers of patients with an ECG that was initially normal with those with an initial ECG with non-specific ST or T wave changes, and with those with a diagnostic ECG (ST elevation or depression and/or left bundle branch block).
4. Main outcome measure = in-hospital mortality; secondary outcome = composite of mortality + adverse in-hospital cardiac events.

1. Of 390 000 patients in whom MI was established, 8% had a normal initial ECG; 35% had a non-specific ECG; 57% had diagnostic ECGs.
2. In-hospital mortality was 6%; 9%; and 12% respectively. (Note that those with an initially normal ECG had about half the mortality as those with diagnostic ECGs.)
3. For the composite outcome measure, rates were 19%; 27%; and 35%.
4. There were clinical hints of differences:
         The normal ECG group tended to be younger, male, to have a lower rate of prior MI, and a lower rate of history of congestive failure. Fewer arrived at the hospital within 6 hours of onset of symptoms. Symptoms were more likely to be atypical. More were admitted to the monitoring unit than to intensive care. More developed non-Q-wave MI. Fewer were treated with aspirin.
5. Among those with an initially normal or non-specific ECG, about 1/5 went on to develop frank ST elevation or left bundle branch block on subsequent ECGs.
6. Mortality was higher in subgroups of patients within the 3 ECG groups. Those presenting at age greater than 75, with tachycardia, and evidence of congestive failure (rales and jugular venous distention), as well as those presenting without chest pain had a higher risk of death. Mortality was lower in men younger than 65 who had an ejection fraction of 40% or greater.

1. Patients presenting with symptoms compatible with acute MI who had initially normal or non-specific ECGs had lower, but clinically significant, short-term mortality rates compared with those with initially diagnostic ECGs.
2. "The unexpected finding of this study was that patients with an initially normal ECG had a substantial mortality rate, one that approximates the 30-day risk for patients with ST-segment elevation treated in recent trials of reperfusion therapies."
3. In patients with an acute MI, a normal or non-specific initial ECG does not indicate that the patient will have a favorable hospital course.

1. Community-based study of over 3 successive winters obtained nasopharyngeal swabs from patients with influenza-like illness. Examined them for RSV and IV by polymerase chain reaction.
2. Related findings to the clinical incidence of influenza-like illness and acute bronchitis.

1. Of a total of over 2200 swabs, 480 were positive for RSV and 709 positive for IV. Both types were identified in all age groups for between 12 and 20 weeks each winter.
2. Age distribution over 3 winters:

   Age	Influenza positive	RSV positive
   15-44	31%	20%
   45-64	29%	19%

1. In each of 3 winter seasons, RSV was identified in community-dwelling individuals of all age groups diagnosed as having influenza-like illness. "RSV is therefore an important pathogen contributing to the burden of illness in the entire community in winter."
2. The relative proportions of the two viruses changed over the seasons. More were positive for IV during the peak of the influenza-like illness.
3. In most cases the pathogen isolated can be assumed to have caused the illness. Nevertheless, there was a minority of patients who had both viruses present at the same time.
4. The frequency of acute bronchitis in winter is always substantially higher than that ascribed to influenza. The authors believe that at least some of these cases are due to RSV.
5. In the UK, the excess mortality of RSV infections is estimated at about 22 000 per year. Hospital admissions reflect this.
6. This study reaffirms the need for continuous surveillance of RSV as an important public-health issue. It raises the question of a rational vaccination policy for both IV and RSV.
7. In addition, when the two illnesses occur simultaneously in the community, there is a need to distinguish between the two if specific antiviral treatment is to be prescribed.

1. The community-based Framingham study has gathered long term information about cardiovascular risks. Over 5000 stroke-free subjects were enrolled from 1948 to 1953. All were followed to the end of 1998.
2. Determined 10-year risk of initial ischemic stroke for decades beginning with age 60, 70, and 80. (Eg, for a 40 year old subject enrolled in 1950 and reaching age 60 alive and without stroke, the study provided information on the occurrence of stroke in the decade 60 to 70.) If the same individual reached the age of 70 free of stroke, he or she provided an additional 10 years of follow-up from age 70 to 80.
3. Considered 3 aspects of BP:

   Current BP (time of risk prediction at baseline ó age 60, age 70, or age 80)
   Recent BP ó average of determinations of BP in the decade preceding. Ie, for an individual age 60, the average BP during age 50 to 60.)
   Remote BP ó average of determinations of BP 10 to 20 years before baseline. (Ie, for an individual age 60 at baseline, his or her average BP during age 40 to 50.)
   

1. Almost 500 strokes were observed.

   A.

   Recent antecedent BP: In subjects age 60 at baseline followed for 10 years, the recent antecedent BP (at age 50-59) influenced incidence of stroke between age 60 and 70. Relative risk of stroke per standard deviation increment from the mean BP during ages 50-59 was 1.8. In subjects age 70 at baseline followed for 10 years, the recent antecedent BP (at age 60-69) influenced incidence of stroke between age 70-79. Relative risk of stroke per standard deviation increment from the mean BP during ages 60-69 was 1.5.

   B.

   Remote antecedent BP: Similar increases in incidence of stroke were seen in those whose BP was elevated 10 to 20 years prior.

2. The effect was evident for recent and remote antecedent BP in hypertensive and non-hypertensive subjects, and demonstrable for systolic, diastolic and pulse pressures.
3. As expected, higher levels of BP at baseline (eg, age 60) predicted a greater incidence of stroke during the decade 60-69.

1. The risk of stroke doubles in each successive decade after age 55. The great majority of strokes occur after age 65.
2. The cumulative effect of long-term exposure to an elevated BP may partly explain this age-associated increase in risk. Antecedent BP levels were associated with increased risk of ischemic stroke even after adjustment for current BP levels. The effect was robust.
3. In the Framingham study, about 1/4 of strokes occurred in individuals whose current BP was in the non-hypertensive range. "While this is not entirely surprising, given the continuum of risk, the importance of past BP elevation as a potentially modifiable risk factor for prevention of stroke in this group should not be overlooked."
4. The study strongly suggests that midlife BP levels continue to affect the future risk of stroke not only over a short span, but over more prolonged periods, up to 30 years.
5. "While the reduction in risk achieved by antihypertensive treatments is impressive at any age, and particularly in elderly persons, treatment of hypertension in older subjects who have been exposed to elevated BP levels for many years leaves their risk well above that of nonhypertensive subjects."
6. To achieve optimal reductions in risk of stroke in elderly persons it may be necessary to prevent, diagnose, and manage BP elevations throughout adulthood.

1. Measured BNP in plasma of over 2500 patients obtained a mean of 40 hours after onset of ischemic symptoms.
2. All met one or more of the following entrance criteria: ECG changes (ST depression or elevation of at least 0.5 mm, T wave inversion of at least 3mm in at least 3 leads, or left bundle branch block); elevated levels of cardiac markers; a history of coronary disease; or age > 65 in patients with diabetes or vascular disease.
3. Correlated BNP levels with clinical outcomes.

1. Height of BNP was correlated with the risk of death, heart failure, and MI at 30 days and 10 months.
2. The rate of death increased in a stepwise fashion as levels of BNP increased. Odds ratios of death at 10 months in the second, third and fourth quartiles of BNP were 4, 4, and 6 compared with those in the first quartile. The association remained significant in those with ST elevation MI, those with MI without ST elevation, and in those with unstable angina.
3. A level of BNP more than 80 pg/mL was associated with the risk of new or recurrent MI, and new or worsening heart failure and death.

1. A single measurement of BNP obtained within a few days of onset of ischemic symptoms provided powerful risk-stratification information across the entire spectrum of acute coronary syndromes.
2. "Activation of the cardiac neurohormonal system may be a unifying feature among patients at high risk of death after acute coronary syndromes."
3. The association between BNP and long term risk of death was independent of presence or absence of heart failure (HF), troponin I levels, ECG changes, and other known predictors.
4. High level of BNP was associated with an increased risk of non-fatal endpoints ó new progressing HF, and MI.
5. A level of 80 pg/mL is an appropriate predictive threshold among patients with acute coronary syndromes.
6. Previous studies have indicated that, after an acute MI, a higher level of BNP is associated with a larger infarct, increased likelihood of ventricular remodeling, a lower ejection fraction, and increased likelihood of HF and death.
7. Unlike traditional cardiac biomarkers used to predict risk among patients with acute coronary syndromes, BNP has a putative role in the counter-regulatory response to ischemia. It may act as an index of the degree of underlying impairment of left ventricular function.
8. Of interest ó The level of BNP increases rapidly and transiently after exercise testing in patients with chronic stable angina. The degree of elevation is correlated with the size of the ischemic area.
9. These findings suggest that the prognostic implications of BNP are distinct from those of myocardial necrosis, including patients with unstable angina and those without troponin I elevation.
10. For a biomarker to be clinically useful, it must help clinicians select appropriate therapy. Patients with elevated troponin I after acute coronary syndromes appear to derive benefit from an early aggressive strategy that includes potent antiplatelet and antithrombotic therapy and early revascularization. Patients with a high BNP may therefore benefit from more intensive interventions ó antiplatelet, antithrombotic, beta-blockade, ACE inhibition, and early revascularization.
11. Equally importantly, patients who have normal BNP after an acute event appear to have a particularly low long-term risk of death and heart failure. Less intense management may be appropriate in this group.