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BACKGROUND: Research and therapy only has relevance when applied to an actual patient. OBJECTIVE: To review a case study of a patient with hypertension and diabetes. SUMMARY: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) of 2004 recommends that a diagnostic workup include an assessment of risk factors and comorbidities using history, physical exam, and laboratory parameters. The presence of comorbidities influences drug selection. Patient evaluation should also include identification of possible causes of hypertension, such as renal arterial stenosis, and an assessment for the presence of target organ damage. Treatment is always influenced by the presence or absence of comorbidities. Lifestyle modifications are crucial to enhancing the success of pharmacologic therapy and should be ongoing. If lifestyle modifications do not work, the clinician must consider drugs. Study data and JNC 7 recommend beta-blockers for hypertension in patients with compelling indications, e.g., high risk for cardiovascular disease and diabetes. CONCLUSION: JNC 7 emphasizes that evaluation for hypertension includes the assessment for the presence of compelling indications, e.g., diabetes, hyperlipidemia, and high coronary risk. These comorbidities may inform and direct pharmacologic choices.

Understanding Statin Use in America and Gaps in Education (USAGE) is a cross-sectional, self-administered internet-based survey of US adults with a reported history of high cholesterol and statin use. Respondents were categorized as current or former statins users; and by whether they had ever experienced new or worsening muscle pain on a statin, and/or ever stopped a statin because of muscle-related symptoms. Chi-square and ttests were used to assess associations among variables. Results

Hypertension management is both routine and a challenge. Updated guidelines emphasize the need to achieve increasingly stringent blood pressure goals to reduce cardiovascular morbidity and mortality; however, the blood pressure of many patients who have been diagnosed with hypertension is not well controlled. Treating prehypertension nonpharmacologically may preempt the progression to hypertension, whereas early and aggressive management of hypertension with antihypertensive agents reduces short- and long-term cardiovascular risk. Treatment decisions should follow current guidelines while evaluating recently published clinical studies. When choosing between agents from different therapeutic classes or combining agents, physicians should consider current and targeted blood pressure levels, the patient's demographic profile, the presence or absence of compelling cardiovascular and metabolic indications, other comorbidities, and concurrent medication(s).

Knowledge of predictors of diabetes mellitus (DM) development in patients with coronary artery disease (CAD) who use antihypertensive therapy could contribute to decreasing this adverse metabolic consequence. This is particularly relevant because the standard of care, beta blockers combined with diuretics, may contribute to adverse metabolic risk. The INternational VErapamil SR-trandolapril STudy compared a calcium antagonist-based (verapamil SR) and a beta-blocker-based (atenolol) strategy with trandolapril and/or hydrochlorothiazide added to control blood pressure (BP) in patients with CAD. The 16,176 patients without DM at entry were investigated with regard to newly diagnosed DM during follow-up. Newly diagnosed DM was less frequent in the verapamil SR versus atenolol strategy (7.0% vs 8.2%, hazard ratio 0.85, 95% confidence interval 0.76 to 0.95, p0.01). Characteristics associated with risk for newly diagnosed DM included United States residence, left ventricular hypertrophy, previous stroke/transient ischemic attack, Hispanic ethnicity, coronary revascularization, hypercholesterolemia, greater body mass index, and higher follow-up systolic BP. Addition of trandolapril to verapamil SR decreased DM risk and addition of hydrochlorothiazide to atenolol increased risk. In conclusion, clinical findings associated with more severe vascular disease and Hispanic ethnicity identify a group at high risk for developing DM, whereas lower on-treatment BP and treatment with verapamil SR-trandolapril attenuated this risk.

The large proportion of the population who have only modest or moderate hypercholesterolemia will experience more coronary events than the smaller percentage of people who are at higher risk from more extreme elevations of serum cholesterol. The high-risk individual strategy for prevention of coronary heart disease (CHD) can result in impressive declines in cholesterol, but the benefits will be concentrated at the upper end of the population distribution. On the other hand, a population strategy for coronary disease prevention will achieve a much more modest reduction of cholesterol, but these changes will be over the entire distribution and will reduce the risk of the much larger proportion of people with average cholesterol levels who otherwise would likely go untreated. In light of the fact that epidemiologic studies and long-term clinical trials predict that a 10% reduction in serum cholesterol will result in a 30% reduction in coronary events, the population strategy has the potential for an enormous impact in reducing CHD, which, despite our great success over the past two decades, still remains the number one killer in the United States.

To examine the long-term association of metabolic syndrome with mortality among those at high risk for cardiovascular disease (CVD).A total of 10,950 Multiple Risk Factor Intervention Trial (MRFIT) survivors were followed for mortality an additional median 18.4 years (1980-1999). Proportional hazards models examined multivariate-adjusted risks associated with Adult Treatment Panel III-defined metabolic syndrome conditions, with BMI substituted for waist circumference.At MRFIT annual visit 6, 4,588 (41.9%) men, mean age (+/-SD) 53.0 +/- 5.9 years, had metabolic syndrome and 6,362 did not. Comparing men with metabolic syndrome to men without, adjusted hazard ratios (HRs) were 1.21 (95% CI 1.13-1.29), 1.49 (1.35-1.64), and 1.51 (1.34-1.70) for 18-year total, CVD, and coronary heart disease mortality, respectively. Among men with metabolic syndrome, elevated glucose (1.54 [1.34-1.78]) and low HDL cholesterol (1.45 [1.17-1.54]) were most predictive of CVD mortality, followed by elevated BMI (1.34 [1.17-1.54]), elevated blood pressure (1.25 [0.98-1.58]), and elevated triglycerides (1.06 [0.86-1.30]). In contrast, for men without metabolic syndrome, the HR for low HDL cholesterol was 1.02 (0.86-1.22). Among metabolic syndrome men with no nonfatal CVD event, smokers with elevated LDL cholesterol showed higher CVD mortality (1.79 [1.22-2.63]) compared with nonsmokers without elevated LDL cholesterol; this additional risk was even greater for metabolic syndrome men with a nonfatal CVD event (2.11 [1.32-3.38]).Metabolic syndrome is associated with an increased risk of mortality. Among those with metabolic syndrome, risk is further increased by having more metabolic syndrome conditions, by cigarette smoking, and by elevated LDL cholesterol. Primary prevention of each metabolic syndrome condition should be emphasized, and presence of each condition should be treated in accordance with current guidelines.

BACKGROUND Epidemiologic, laboratory, animal, and clinical studies suggest that there is an association between Chlamydia pneumoniae infection and atherogenesis. We evaluated the efficacy of one year of azithromycin treatment for the secondary prevention of coronary events. METHODS In this randomized, prospective trial, we assigned 4012 patients with documented stable coronary artery disease to receive either 600 mg of azithromycin or placebo weekly for one year. The participants were followed for a mean of 3.9 years at 28 clinical centers throughout the United States. RESULTS The primary end point, a composite of death due to coronary heart disease, nonfatal myocardial infarction, coronary revascularization, or hospitalization for unstable angina, occurred in 446 of the participants who had been randomly assigned to receive azithromycin and 449 of those who had been randomly assigned to receive placebo. There was no significant risk reduction in the azithromycin group as compared with the placebo group with regard to the primary end point (risk reduction, 1 percent [95 percent confidence interval, -13 to 13 percent]). There were also no significant risk reductions with regard to any of the components of the primary end point, death from any cause, or stroke. The results did not differ when the participants were stratified according to sex, age, smoking status, presence or absence of diabetes mellitus, or C. pneumoniae serologic status at baseline. CONCLUSIONS A one-year course of weekly azithromycin did not alter the risk of cardiac events among patients with stable coronary artery disease.

Two online surveys commissioned by the National Lipid Association (NLA) were conducted to determine the current attitudes of physicians and consumers regarding cholesterol and heart disease. Physicians and consumers from preexisting independent panels were randomly invited to participate in the online surveys that were open from January 26 to 30, 2004. Both physicians (n = 200) and consumers (n = 600) agreed that high cholesterol and coronary artery disease (CAD) are significant health risks. Physicians reported the primary barriers for patients being prescribed cholesterol-lowering medication as patient fear of side effects (61%) and reluctance to take prescription medications (52%). While most physicians were aware of and felt they adhered to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, considerably fewer thought the same of other physicians. The consumer survey focused on untreated moderate-risk patients (an approximate 10% to 20% 10-year risk of myocardial infarction and cardiac death) because this group is often undertreated. Untreated moderate-risk patients reported that their physicians did not advise them to take prescription cholesterol-lowering drugs (51%) and that they were trying to control their cholesterol with diet and exercise (58%). Consumers believe they are taking an increased role in their own health management and decision making. Current attitudes of physicians and consumers are similar with regard to their recognition of the significance of cholesterol and CAD for health, but differ with regard to why patients do not take prescription medications.

To report long-term risks for total, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality associated with incident diabetes (using current diagnostic criteria) and with incident nonfatal CVD (NF-CVD).A total of 11645 participants without diabetes or CVD at baseline from the Multiple Risk Factor Intervention Trial who survived to the end of the trial were grouped by during-trial incident diabetes and/or NF-CVD events: neither diabetes nor NF-CVD, diabetes only, NF-CVD only, or both diabetes and NF-CVD. Incident diabetes was defined by use of hypoglycemic agents or fasting glucoseor=126 mg/dl at any time over the 6 trial years. Proportional hazards models tested group differences in mortality over 18 post-trial years.Among 3859 total deaths were 1846 from CVD and 1277 from CHD, with death rates per 10000 person-years of 203, 97, and 67, respectively. Multivariate-adjusted hazard ratios (HRs) for total mortality were 2.75 (P0.0001) for those with NF-CVD and diabetes both, 1.92 (P0.0001) for those with NF-CVD only, and 1.49 (P0.0001) for those with diabetes only, relative to neither diabetes nor NF-CVD. NF-CVD was associated with a higher hazard of death than diabetes for total (HR 1.29, P = 0.0004), CVD (HR 1.76, P0.0001), and CHD (HR 1.88, P0.0001) mortality. Only the subgroup of participants on hypoglycemic agents showed an equivalent risk of total mortality relative to participants with NF-CVD (HR 0.93, P = 0.54).Current diabetes diagnostic criteria conferred significantly increased total, CVD, and CHD mortality risks independent of the impact of NF-CVD. NF-CVD was more strongly predictive of mortality.

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

The safety and efficacy of two fixed dose combinations of enalapril and diltiazem extended release formation (ER) (E/D) were compared with their monotherapies and placebo in patients with stage 1 to 3 hypertension. The trial design was a multicenter, randomized, double blind, placebo controlled, parallel group, 12 week treatment phase, followed by a 36 week, open label phase. A total of 891 patients with sitting diastolic blood pressure (SiDBP) between 95 and 115 mm Hg were randomly assigned to enalapril 5 mg, diltiazem ER 120 mg, diltiazem ER 180 mg, enalapril 5 mg/diltiazem ER 120 mg (E5/D120), enalapril 5 mg/ diltiazem ER 180 mg (E5/D180), or placebo. In the open label phase, 562 patients received the fixed combination, titrated as needed to control SiDBP < 90 mm Hg. Efficacy was determined with trough (24 +/- 2 h postdose) sitting blood pressure measurements at week 12 and at the end of the open label part of the study. Safety was evaluated based on patient symptoms, clinical laboratories, and electrocardiograms (ECG). E5/D120 and E5/D180 significantly reduced trough SiDBP (-7.6 and -8.3 mm Hg, respectively; P < .05) versus their monotherapies. E5/D120 and E5/D180 significantly reduced trough sitting systolic blood pressure (-7.9 and -9.0, respectively; P < .05) versus both diltiazem ER monotherapies. All active treatments significantly decreased SiDBP and SiSBP versus placebo. E/D effectively lowered SiDBP and SiSBP during the open label extension. No significant difference was seen among treatment groups for the overall incidence of adverse events. The most common drug related adverse events were headache, edema/swelling, dizziness, asthenia/fatigue, cough, rash, and impotence. The event frequency for the combinations were similar to those seen with the monotherapies. Fixed combinations of E/D were generally well tolerated, with an increased blood pressure lowering effect as compared with the individual components in patients with stage I to III hypertension.

Objective This study evaluated physiological, neuroendocrine, and psychological status and functioning of patients with coronary artery disease in order to clarify their role in the expression of symptoms during myocardial ischemia (MI), and to establish repeatability of responses to mental stress. Design and methods of the study are presented. Methods One hundred ninety-six coronary artery disease patients were examined during physical and mental stress tests in four hospitals. Eligibility criteria included narrowing of at least 50% in the diameter of at least one major coronary artery or verified history of myocardial infarction, and evidence of ischemia on an exercise treadmill test. Psychological, biochemical, and autonomic function data were obtained before, during, and after exposure to mental and exercise stressors during 2 or 3 half-days of testing. Ventricular function was assessed by radionuclide ventriculography, and daily ischemia by ambulatory electrocardiography. Sixty patients returned for a short-term mental stress repeatability study. Twenty-nine individuals presumed to be free of coronary disease were also examined to establish reference values for cardiac responses to mental stress. Results Study participants were 41 to 80 years of age; 83 (42%) had a history of MI, 6 (3%) of congestive heart failure, and 163 (83%) of chest pain; 170 (87%) were men; and 90 (46%) had ischemia accompanied by angina during exercise treadmill testing. Ischemia during ambulatory monitoring was found in 35 of 90 (39%) patients with and 48 of 106 (45%) patients without angina during exercise-provoked ischemia. Intraobserver variability of ejection fraction changes during bicycle exercise and two mental stress tests (Speech and Stroop) was good (kappa = 1.0, .90, and .76, respectively; percent agreement = 100, 97.5, and 93.8%, respectively). Variability of assessed wall motion abnormalities during bicycle exercise was better (kappa, agreement = 85%) than during Speech or Stroop kappa and .57, percent agreement = 70% and 82.5%, respectively). Conclusions Study design, quality control data, and baseline characteristics of patients enrolled for a clinical study of symptomatic and asymptomatic myocardial ischemia are described. Lower repeatability of reading wall motion abnormalities during mental stress than during exercise may be due to smaller effects on wall motion and lack of an indicator for peak mental stress.

Background The normal cardiovascular response to mental stress in middle-aged and older people has not been well characterized. Methods and Results We studied 29 individuals 45 to 73 years old (15 women, 14 men) who had no coronary risk factors, no history of coronary artery disease, and a negative exercise test. Left ventricular (LV) volumes and global and regional function were assessed by radionuclide ventriculography at rest and during two 5-minute standardized mental stress tasks (simulated public speaking and the Stroop Color-Word Test), administered in random order. A substantial sympathetic response occurred with both mental stress tests, characterized by increases in blood pressure, heart rate, rate-pressure product, cardiac index, and stroke work index and rises in plasma levels of epinephrine and norepinephrine but not β-endorphin or cortisol. Despite this sympathetic response, LV volume increased and ejection fraction (EF) decreased secondary to an increase in afterload. The change in EF during mental stress varied among individuals but was associated positively with changes in LV contractility and negatively with baseline EF and changes in afterload. EF decreased >5% during mental stress in 12 individuals and >8% in 5; 3 developed regional wall motion abnormalities. Conclusions Mental stress in the laboratory results in a substantial sympathetic response in normal middle-aged and older men and women, but EF commonly falls because of a concomitant rise in afterload. These results provide essential age- and sex-matched reference data for studies of mental stress–induced ischemia in patients with coronary artery disease.

Background The pathophysiology of mental stress–induced myocardial ischemia, which occurs at lower heart rates than during physical stress, is not well understood. Methods and Results The Psychophysiological Investigations of Myocardial Ischemia Study (PIMI) evaluated the physiological and neuroendocrine functioning in unmedicated patients with stable coronary artery disease and exercise-induced ischemia. Hemodynamic and neurohormonal responses to bicycle exercise, public speaking, and the Stroop test were measured by radionuclide ventriculography, ECG, and blood pressure and catecholamine monitoring. With mental stress, there were increases in heart rate, systolic blood pressure, cardiac output, and systemic vascular resistance that were correlated with increases in plasma epinephrine. During exercise, systemic vascular resistance fell, and there was no relationship between the hemodynamic changes and epinephrine levels. The fall in ejection fraction was greater with mental stress than exercise. During mental stress, the changes in ejection fraction were inversely correlated with the changes in systemic vascular resistance. Evidence for myocardial ischemia was present in 92% of patients during bicycle exercise and in 58% of patients during mental stress. Greater increases in plasma epinephrine and norepinephrine occurred with ischemia during exercise, and greater increases in systemic vascular resistance occurred with ischemia during mental stress. Conclusions Mental stress–induced myocardial ischemia is associated with a significant increase in systemic vascular resistance and a relatively minor increase in heart rate and rate-pressure product compared with ischemia induced by exercise. These hemodynamic responses to mental stress can be mediated by the adrenal secretion of epinephrine. The pathophysiological mechanisms involved are important in the understanding of the etiology of myocardial ischemia and perhaps in the selection of appropriate anti-ischemic therapy.

Angiotensin-converting enzyme inhibitors and calcium antagonists are 2 classes of antihypertensive agents frequently used either as monotherapy or in combination. A 6-week, multicenter, randomized, double-blind, placebo-controlled trial was conducted in essential hypertensive patients (diastolic blood pressures [BP] when seated, 95-115 mm Hg) to evaluate the efficacy, dose response, and safety profiles of enalapril combined with a new once-daily formulation of diltiazem. BP and heart rate were measured at 5 (peak) and 24 (trough) hours after dose to assess the efficacy and pharmacodynamic profile of the combination given once daily. There were 336 patients randomly assigned to either enalapril 5 mg plus 1 of 4 dose levels of diltiazem ER (60, 120, 180, or 240 mg), enalapril 5 mg alone, or placebo. Each combination dose level produced statistically significant reductions (p0.05) in trough diastolic BP when seated, compared with placebo (-6.8, -8.3, -10.1, and -10.3 mm Hg for the diltiazem ER doses of 60, 120, 180, and 240 mg, respectively). The 3 highest combination dose levels resulted in statistically significant (p0.05) decreases in trough diastolic BP when seated, compared with placebo. There was a significant (p0.001) linear dose-response relation. A trough-to-peak ratioor = 0.5 was shown for the 3 highest combination doses. Drug-related adverse events were seen in 8.9% to 19% of the combination patients, 14.3% of the enalapril patients, and 8.6% of the placebo patients. The frequency and type of adverse events were those currently noted with each drug studied when used as monotherapy.

Psychological factors are linked to outcomes in coronary artery disease (CAD) pts but the mechanisms are obscure. The PIMI is a NIH multicenter study designed to test the overall hypothesis that manifestations and expressions of ischemia are influenced by specific psycho-physiologic mechanisms. Accordingly, 200 pts, mean age 62, with CAD and ischemia responses on treadmill were studied. Ambulatory ECG (AECG) monitoring, psychological instrument batteries and plasma biochemical tests were applied to identify mechanisms associated with ischemia during daily life, exercise and mental stress without influence of cardiac medications. Daily life ischemia (AECG) occurred in 41% of pts (95% with ischemia were asymptomatic) and was associated with lower hostility (p l 0.01) and anger expression (p l 0.03) scores compared with those without daily life ischemia. An inverse association between magnitude of daily life ischemia and these scores was observed. No differences were found for depression (Beck) or anxiety scores. On treadmill all pts had ischemia (ST segment depression) but 44% had angina. Angina expression was associated with higher depression (p =0.002), anxiety (State, p = 0.002 and Trait, p = 0.01) and autonomic perception (p = 0.05) scores than no angina. Depression best predicted time to angina (Cox model, p = 0.007). During mental stress (Stroop and speech tasks) ischemia (radionuclide ventriculogram (RVG) or ST segment abnormalities) occurred in 79% of pts (95% with ischemia were asymptomatic) and associated with higher Reward, Dependence, (Temperament and Character Inventory, p l 0.02) and level of irritation during Stroop task (p l 0.01). Plasma norepinephrine remained low, but epinephrine doubled and systolic pressure increased. No associations were found for medical or demographic factors examined. During bicycle exercise ischemia (RVG abnormality) occurred in 94% of pts (64% with ischemia were asymptomatic) yet norepinephrine increased three-fold. In summary, daily life ischemia (usually asymptomatic) is associated with suppressed hostility, anger and emotion but not depression or anxiety. Mental stress ischemia (mostly asymptomatic and with epinephrine release) is related to temperament characteristics. Exercise stress ischemia, on the other hand, more often evokes symptoms and marked norepinephrine release but symptom expression seems dependent upon depression, anxiety and autonomic perception. Mechanisms responsible for ischemia evoked in different settings and its symptomatic expression involve complex interactions of behavioral, physiological and psychophysiological factors.

Effective treatment of hypertension in the elderly requires an understanding of both the progressive course of the disease and the impact of aging on the cardiovascular system, including physiological, genetic, lifestyle, and environmental factors. Review of the literature that has attempted to define the impact of an “aging process” on cardiovascular structure and function reveals a diversity of findings and interpretations. However, in general, normotensive elderly subjects exhibit the heart and vascular characteristics of “muted” hypertension, including many features of younger hypertensive patients: cardiac hypertrophy, diminution in resting left ventricular early diastolic filling rate, increased arterial stiffness and aortic impedance, diminution in the baroreceptor reflex, a diminished response to catecholamines and diminished renal blood flow, and an increase in peripheral vascular resistance (PVR). Treatment of elderly hypertensives is more challenging because of the greater likelihood of the presence of concomitant diseases, most importantly, coronary and peripheral atherosclerosis, renal dysfunction, and diabetes mellitus. Isolated systolic hypertension (ISH), the most common form of hypertension in the elderly, has also been clearly shown to be an important predictor of cardiovascular morbidity and mortality, including coronary artery disease, congestive heart failure, and stroke. Treatment of ISH has been shown to lower systolic pressure safely and effectively in the elderly. By reducing PVR, and possibly the arterial stiffness, and thus the early reflected pulse waves, vasodilators, including calcium antagonists, may lower these three components of arterial impedance, and hence lower the arterial load on the heart. The cardiac hypertrophy and reduced left ventricular filling rate associated with hypertension in older individuals can also be ameliorated, to some extent, by calcium channel blockers.

To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure.Randomized control multicenter trials.Volunteers recruited from the community, treated and followed up at special clinics.Of 16,821 screenees, 2182 men and women, aged 30 through 54 years, with diastolic blood pressure from 80 through 89 mm Hg were selected. Of these, 50 did not return for follow-up blood pressure measurements.Three life-style change groups (weight reduction, sodium reduction, and stress management) were each compared with unmasked nonintervention controls over 18 months. Four nutritional supplement groups (calcium, magnesium, potassium, and fish oil) were each compared singly, in double-blind fashion, with placebo controls over 6 months.Primary: change in diastolic blood pressure from baseline to final follow-up, measured by blinded observers. Secondary: changes in systolic blood pressure and intervention compliance measures.Weight reduction intervention produced weight loss of 3.9 kg (P less than .01), diastolic blood pressure change of -2.3 mm Hg (P less than .01), and systolic blood pressure change of -2.9 mm Hg (P less than .01). Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h (P less than .01), diastolic blood pressure by 0.9 mm Hg (P less than .05), and systolic blood pressure by 1.7 mm Hg (P less than .01). Despite good compliance, neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly (P greater than .05).Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons. Sodium reduction is also effective. The long-term effects of weight reduction and sodium reduction, alone and in combination, require further evaluation.

BACKGROUND Risk factors for pure coronary spasm are not known. Clinical observations have pointed to cigarette smoking, a known risk factor for obstructive coronary artery disease. METHODS AND RESULTS We conducted a case-neighborhood control study of premenopausal women, a population segment with the lowest prevalence of obstructive coronary artery disease. The cases were 21 premenopausal women (age range, 36-41 years) with angiographically proven coronary spasm. All coronary arteriograms were analyzed by two independent experienced cardiologists on two occasions. There were no differences between analyses; all cases had normal baseline coronary angiogram except for two, who had less than 20% coronary luminal stenosis in segments other than the site of the focal vasospasm. All cases had normal hemodynamics at rest, normal left ventricular function, and were in sinus rhythm. Ascertainment of the cases was done by angiographic demonstration of focal coronary spasm spontaneously or by ergonovine provocation. Six cases developed spontaneous coronary spasm before catheter engagement, and in 15, coronary spasm was induced by ergonovine provocation. Each case was asked to name as many as possible female neighborhood acquaintances of similar age and racial background who were willing to answer the same standardized questionnaire. The same standardized questionnaire was completed for each case and each control (n = 63). The standardized questionnaire was designed to obtain information on health characteristics, habits, socioeconomic status, and education. Only cigarette smoking was significantly more prevalent among coronary spasm cases. Cigarette smokers were 13 cases (62%) and 11 controls (17.5%) (p less than 0.001). The odds ratio was 7.7, with a 95% confidence interval of 2.6-23.1. CONCLUSIONS These findings suggest that there is a very strong association between cigarette smoking and pure coronary spasm in young women.

Phase I of the Trials of Hypertension Prevention (TOHP) was a National Heart, Lung, and Blood Institute-sponsored, 3-year, national, multicenter, randomized, controlled trial designed to test the feasibility and efficacy of three life-style (weight loss, sodium restriction, and stress management) and four nutrition supplement (calcium, magnesium, fish oil, and potassium) interventions aimed at lowering diastolic blood pressure in those whose blood pressure was initially in the high normal range (80 to 89 mm Hg). A total of 2182 volunteers were recruited and allocated to the various treatment arms, such that each hypothesis was tested with a power of 85% or higher to detect a diastolic blood pressure treatment effect of 2 mm Hg. The four nutrition supplement interventions were delivered in a double-blinded fashion and the three life-style interventions, single (observed) -blinded. Phase I was designed to provide a rigorous test of short-term lowering of blood pressure for each of the seven treatments chosen and provides the basis for planning of a subsequent long-term trial of hypertension prevention.

The SHEP is a randomized, placebo-controlled trial that will follow standard clinical trial principles in analyzing data relating to its proposed hypotheses. The protocol has stated a priori the main objective as well as the secondary subgroup hypotheses. Sample size calculations for SHEP have accounted for dropins to and drop-outs from active therapy as well as for the risk of nonstroke death. The sample size achieved (4,736 participants) should be adequate to address the proposed questions. Monitoring procedures have been described and established. A data and safety monitoring board that uses these procedures is closely following the data from the trial. The board will periodically examine the data to determine whether termination of the study is warranted.

Physicians are aware of the value of treating hypertension. Complications such as stroke and congestive heart failure are less likely to occur in the well-controlled patient. In our quest to add coronary heart disease to this list, we must go beyond simple reduction of blood pressure. We must consider other risk factors such as hypercholesterolemia, cigarette smoking, diabetes mellitus, and family history. The presence of one or more of these may indicate a more aggressive treatment approach. Similarly the presence of left ventricular hypertrophy, coronary disease, or renal disease may indicate specific pharmacotherapy. On the other hand, the low-risk patient with no other problems or conditions may be treated with only nonpharmacologic therapy such as weight loss, dietary sodium reduction, and/or alcohol restriction. Every patient has a different constellation of findings. Every patient should be treated individually. It is no longer sufficient just to lower blood pressure; we need to manage the whole patient with hypertension; keeping in mind that most antihypertensive agents are equally effective, the side effect profile is often the decisive factor in choosing an antihypertensive agent.

One hundred four participants in the Systolic Hypertension in the Elderly Program (SHEP) trial (mean age 71 +/- 6 years) were examined by Doppler echocardiography to gain information on the cardiac structural and functional alterations in isolated systolic hypertension. Participants had a systolic blood pressure greater than 160 mm Hg with diastolic blood pressure less than 90 mm Hg and were compared with 55 age-matched normotensive control subjects. Left ventricular mass index was significantly higher in the participants than in the normotensive subjects (103 +/- 28 versus 87 +/- 23 g/m2, p = 0.0014) and 26% of the participants met echocardiographic criteria for left ventricular hypertrophy compared with 10% of normotensive subjects. Left atrial index was also greater in participants than in normotensive subjects (2.26 +/- 0.32 versus 2.11 +/- 0.24 cm/m2, p = 0.005) and 51% of participants had left atrial enlargement. Doppler measures of diastolic filling were significantly different between the two groups, with peak atrial velocity higher (76 +/- 17 versus 69 +/- 17 cm/s, p = 0.02) and ratio of peak early to atrial velocity lower (0.76 +/- 0.23 versus 0.86 +/- 0.22, p = 0.0124) in participants. There was no correlation between left ventricular mass index and Doppler measures of diastolic function, but relative wall thickness correlated significantly with peak atrial velocity (r = 0.22, p = 0.016) and peak early to peak atrial velocity ratio (r = 0.24, p = 0.007). There was no difference in M-mode ejection phase indexes of systolic performance (shortening fraction and peak velocity of circumferential fiber shortening) between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Key Words: Heart failure; diastolic dysfunction. *This activity is supported by an unrestricted educational grant from AstraZeneca.

6. Ismen S. Olsen K, Jacohscn E. IGclscn H, S&en A. Pietensen A. Jensen 0. Pedenen I-‘, Waahcn J. Kehlet H. Hansen J. Dalgaard P. Nyboe J. Predictmu of cardiac risk in non-cardiac surgery. Lur f&w? J I9R7:8:179 18.5. 7. Ashmn C, Pewson Ii. Wray N, Kiefe C. Dunn J. Wu 1.. Thomas J. Ihc mcidence of penoperative myouudial infarctmn in men undergoing noncardiac iurger). Ann /,rrem Mrd lYY3:l 18:504-510.

Weight loss appears to be an effective method for primary prevention of hypertension. However, the long-term effects of weight loss on blood pressure have not been extensively studied.To present detailed results from the weight loss arm of Trials of Hypertension Prevention (TOHP) II.Multicenter, randomized dinical trial testing the efficacy of lifestyle interventions for reducing blood pressure over 3 to 4 years. Participants in TOHP II were randomly assigned to one of four groups. This report focuses only on participants assigned to the weight loss (n = 595) and usual care control (n = 596) groups.Men and women 30 to 54 years of age who had nonmedicated diastolic blood pressure of 83 to 89 mm Hg and systolic blood pressure less than 140 mm Hg and were 110% to 165% of their ideal body weight at baseline.The weight loss intervention included a 3-year program of group meetings and individual counseling focused on dietary change, physical activity, and social supportWeight and blood pressure data were collected every 6 months by staff who were blinded to treatment assignmentMean weight change from baseline in the intervention group was -4.4 kg at 6 months, -2.0 kg at 18 months, and -0.2 kg at 36 months. Mean weight change in the control group at the same time points was 0.1, 0.7, and 1.8 kg. Blood pressure was significantly lower in the intervention group than in the control group at 6, 18, and 36 months. The risk ratio for hypertension in the intervention group was 0.58 (95% CI, 0.36 to 0.94) at 6 months, 0.78 (CI, 0.62 to 1.00) at 18 months, and 0.81 (CI, 0.70 to 0.95) at 36 months. In subgroup analyses, intervention participants who lost at least 4.5 kg at 6 months and maintained this weight reduction for the next 30 months had the greatest reduction in blood pressure and a relative risk for hypertension of 0.35 (CI, 0.20 to 0.59).Clinically significant long-term reductions in blood pressure and reduced risk for hypertension can be achieved with even modest weight loss.

Context.—Left ventricular (LV) hypertrophy is a common problem among elderly patients with isolated systolic hypertension (ISH), but the effect of treatment of ISH on LV mass is not known.Objective.—To assess the ability of antihypertensive drug treatment to reduce LV mass in ISH.Design.—Echocardiographic Substudy of the Systolic Hypertension in the Elderly Program (SHEP).Patients.—A total of 104 participants at the St Louis SHEP site who had interpretable baseline echocardiograms, 94 of whom had 3-year follow-up echocardiograms.Intervention.—The SHEP participants were randomized to placebo or active treatment with chlorthalidone (12.5-25 mg/d), with atenolol (25-50 mg/d) added if necessary to maintain goal blood pressure.Main Outcome Measure.—Change in LV mass assessed by echocardiography.Results.—Minimum follow-up was 3 years. In the active treatment group, 91% and 80% of subjects were receiving treatment with chlorthalidone alone by the end of years 1 and 3, respectively. The LV mass index was 93 g/m2 in the active treatment group and 100 g/m2 in the placebo group (P

Background: This report is part of a larger, multicenter, placebo-controlled study designed to test the effects of low and high salt intake on the antihypertensive action of enalapril maleate or isradipine in salt-sensitive, hypertensive patients. Objective: To present our findings with respect to the effects of race, age, sex, and weight on the blood pressure response to low and high salt intake in salt-sensitive hypertensive patients before randomization into the larger study. Patients and Methods: After 3 weeks (weeks —9 to —6) of ad lib salt intake (100-200 mmol/d of sodium), 1916 patients whose sitting diastolic blood pressure was between 95 and 115 mm Hg entered a 3-week period (week —6 to —3) of low salt intake (50-80 mmol/d of sodium) and then a 3-week period (week —3 to 0) of high salt intake (200-250 mmol/d of sodium). Of the 1916 patients, 624 were identified as being sensitive to salt by demonstrating an increase in sitting diastolic blood pressure of equal to or more than 5 mm Hg from the low to high salt intake. Of these patients, 367 were white, 156 were black, 92 were Hispanic, 8 were Asian, and 1 was American Indian. Also, 315 were men and 309, women; 351 were 55 years or younger and 273 were older than 55 years; and 195 had a body mass index of 27 or less and 429 had a body mass index higher than 27. Results: The sitting blood pressure decreased with salt restriction and increased with salt load in all groups of patients (P Conclusions: This large, multicenter study did not demonstrate any statistically significant effect of race, age, sex, and weight on blood pressure response to salt changes in salt-sensitive hypertensive patients. Arch Intern Med. 1997;157:2489-2494

To the Editor. —Several statements in the letter by Dr Logan and colleagues 1 on dietary sodium and blood pressure (BP) require clarification and correction. First, the authors assert "studies including Intersalt (particularly when data from the 4 primitive societies have been excluded) have found, however, no consistent relationship." 1 In Intersalt analyses on individuals, results were consistent for 10 074 persons from all 52 samples and for 9343 persons from 48 samples (excluding 4 low-sodium samples); the multivariate controlled coefficients for the sodium-systolic BP relationship were—3.1 mm Hg ( P P 2 Results also were similar for nonhypertensives, 2 indicating that "salt sensitivity" is prevalent throughout the population and is not confined mainly to hypertensives. In multivariate cross-population analyses (n=52 and n=48)

To the Editor. —Dr Midgley et al1suggested that a 100-mmol/d reduction in sodium intake would yield an average decrease in blood pressure of 3.7 mm Hg (systolic) and 0.9 mm Hg (diastolic) in hypertensive individuals and 1.0 mm Hg (systolic) and 0.1 mm Hg (diastolic) in normotensive individuals and then questioned the wisdom of current recommendations for moderation in sodium intake in the general population. As the authors point out, many of the 56 trials that formed the basis for their meta-analysis were of questionable quality. Furthermore, the median length of intervention was only 14 days, which is considerably less than desirable for implementation of a behavior change intervention and too short to observe the full effects of a meaningful reduction in sodium intake on blood pressure. As a consequence, the analysis is heavily weighted by results from studies of doubtful relevance to the question at hand. Greater reliance should be

Objectives: To estimate the impact of small reductions in the population distribution of diastolic blood pressure (DBP), such as those potentially achievable by population-wide lifestyle modification, on incidence of coronary heart disease (CHD) and stroke. Design: Published data from the Framingham Heart Study, a longitudinal cohort study, and from the National Health and Nutrition Examination Survey II, a national population survey, were used to examine the impact of a population-wide strategy aimed at reducing DBP by an average of 2 mm Hg in a population including normotensive subjects. Setting/Participants: White men and women aged 35 to 64 years in the United States. Main Outcome Measures: Incidence of CHD and stroke, including transient ischemic attacks (TIAs). Results: Data from overviews of observational studies and randomized trials suggest that a 2—mm Hg reduction in DBP would result in a 17% decrease in the prevalence of hypertension as well as a 6% reduction in the risk of CHD and a 15% reduction in risk of stroke and TIAs. From an application of these results to US white men and women aged 35 to 64 years, it is estimated that a successful population intervention alone could reduce CHD incidence more than could medical treatment for all those with a DBP of 95 mm Hg or higher. It could prevent 84% of the number prevented by medical treatment for all those with a DBP of 90 mm Hg or higher. For stroke (including TIAs), a population-wide 2—mm Hg reduction could prevent 93% of events prevented by medical treatment for those with a DBP of 95 mm Hg or higher and 69% of events for treatment for those with a DBP of 90 mm Hg or higher. A combination strategy of both a population reduction in DBP and targeted medical intervention is most effective and could double or triple the impact of medical treatment alone. Adding a population-based intervention to existing levels of hypertension treatment could prevent an estimated additional 67 000 CHD events (6%) and 34 000 stroke and TIA events (13%) annually among all those aged 35 to 64 years in the United States. Conclusions: A small reduction of 2 mm Hg in DBP in the mean of the population distribution, in addition to medical treatment, could have a great public health impact on the number of CHD and stroke events prevented. Whether such DBP reductions can be achieved in the population through lifestyle interventions, in particular through sodium reduction, depends on the results of ongoing primary prevention trials as well as the cooperation of the food industry, government agencies, and health education professionals. (Arch Intern Med. 1995;155:701-709)

Objective To study the effects of moderate doses of fish oil on blood pressure and high-density lipoprotein (HDL)-cholesterol. Methods The participants were 350 normotensive men and women aged 30-54 years who were enrolled from seven academic medical centers in phase I of the Trials of Hypertension Prevention. They were randomly assigned to receive placebo or 6 g purified fish oil once a day, which supplied 3 g n-3 polyunsaturated fatty acids for 6 months. Results Baseline blood pressure was (mean +/- SD) 123 +/- 9/81 +/- 5 mmHg. The mean differences in the blood pressure changes between the fish oil and placebo groups were not statistically significant. There was no tendency for fish oil to reduce blood pressure more in subjects with baseline blood pressure in the upper versus the lower quartile (132/87 versus 114/75 mmHg), low habitual fish consumption (0.4 versus 2.9 times a week) or low baseline plasma levels of n-3 fatty acids. Fish oil increased HDL2-cholesterol significantly compared with the placebo group. Subgroup analysis showed this effect to be significant in the women but not in the men. Increases in serum phospholipid n-3 fatty acids were significantly correlated with increases in HDL2-cholesterol and decreases in systolic blood pressure. Conclusion Moderate amounts of fish oil (6 g/day) are unlikely to lower blood pressure in normotensive persons, but may increase HDL2-cholesterol, particularly in women.

Objective. —To test the hypothesis that in survivors of myocardial infarction, the suppression of ventricular premature depolarizations improves survival free of cardiac arrest and arrhythmic death. Design. —International, prospective, multicenter, randomized, placebo-controlled trial. Setting. —University and community hospitals. Patients. —A total of 3549 patients with myocardial infarction and left ventricular dysfunction. Intervention. —Administration of encainide, flecainide, moricizine, or placebo to suppress ventricular premature depolarizations. Main Outcome Measures. —Overall survival and survival free of cardiac arrest or arrhythmic death were compared in patients randomized to long-term, active antiarrhythmic drug therapy vs corresponding placebo, using the stratified log rank statistic. Results. —At 1 year from the time of randomization to blinded therapy, 95% of placebo-treated patients vs 90% of active drug—treated patients remained alive ( P =.0006). Similarly, at 1 year, 96% of placebo-treated patients vs 93% of active drug—treated patients remained free of cardiac arrest or arrhythmic death ( P =.003). Conclusions. —The suppression of asymptomatic or mildly symptomatic ventricular arrhythmias after myocardial infarction does not improve survival and can increase mortality. Treatment strategies designed solely to suppress these arrhythmias should no longer be followed. ( JAMA . 1993;270:2451-2455)

In Reply. —This study provided a clear answer to the two questions prompting the study: It showed that one in 20 MRFIT participants with mild to moderate hypertension (DBP, 90 to 115 mm Hg) lost renal function at a rate placing them at substantial risk for the development of end-stage renal disease; furthermore, treatment that reduced diastolic pressure lower than 95 mm Hg removed this risk. The identification of risk associated with this hypertensive group and the recognition that the risk appears to be removed by adequate treatment are findings with important implications for prevention of hypertension-related end-stage renal disease. 1 Failure to demonstrate benefit from treatment among blacks is a finding of concern and importance. The numbers of blacks in this group were not small compared with data previously available, 2 and the findings cited above persisted after controlling for possibly confounding factors. Differences in mean reciprocal creatinine slope

A program was developed to improve independence, self-esteem, and glycemic control in patients with diabetes and blindness. Twenty-nine individuals with both insulin-dependent and noninsulin-dependent diabetes mellitus entered 12-week programs that included education focusing on diabetes self-management skills for the visually impaired, monitored exercise sessions, and group support. Glycated hemoglobin values fell from 13.0% +/- 0.6% (SEM) to 11.4% +/- 0.5% (P = .001). Exercise tolerance in a 12-minute walk test improved from 0.48 +/- 0.04 to 0.64 +/- 0.05 miles (P = .001). Marked improvements occurred in psychosocial indices, demonstrated through changes in the Rand Mental Health Index from 155 +/- 6 to 174 +/- 5 (P = .0001), the Rosenberg Self-Esteem Scale from 22 +/- 1 to 19 +/- 1 (P = .001), the Zung Depression Scale from 0.50 +/- 0.02 to 0.44 +/- 0.02 (P = .001), and the Diabetes Self-Reliance Test from 60 +/- 3 to 74 +/- 2 (P = .0001).

Risk factor status for cardiovascular disease is affected by life style. Adolescence is a time during which long term life-style habits, including dietary habits, are established. Physicians who treat adolescent patients have a responsibility to be aware of the scientific evidence on the diet-heart question so that they can provide their patients with sound dietary advice. The American Heart Association has recommended that Americans consume a "prudent diet" in which daily consumption of cholesterol is no more than 300 mg with up to 30-35% of calories derived from fat, and less than 10% of calories derived from saturated fat and less than 10% from polyunsaturated fat. This paper reviews this recommendation with particular reference to studies of adolescents. This review centers around four main issues: 1) the estimated effect on serum cholesterol levels of a switch from the usual American diet to the prudent diet; 2) the effect of a predicted decrease in serum cholesterol on the risk of developing cardiovascular disease; 3) evaluation of the evidence of possible adverse effects of the prudent diet; 4) feasibility of the prudent diet. Based on a review of these four issues, the authors feel that the American Heart Association's prudent diet should be strongly recommended for all healthy adolescents.