A novel programme to evaluate and communicate 10-year risk of CHD reduces predicted risk and improves patients' modifiable risk factor profile.

AIMS: We assessed whether a novel programme to evaluate/communicate predicted coronary heart disease (CHD) risk could lower patients' predicted Framingham CHD risk vs. usual care. METHODS: The Risk Evaluation and Communication Health Outcomes and Utilization Trial was a prospective, controlled, cluster-randomised trial in nine European countries, among patients at moderate cardiovascular risk. Following baseline assessments, physicians in the intervention group calculated patients' predicted CHD risk and were instructed to advise patients according to a risk evaluation/communication programme. Usual care physicians did not calculate patients' risk and provided usual care only. The primary end-point was Framingham 10-year CHD risk at 6 months with intervention vs. usual care. RESULTS: Of 1103 patients across 100 sites, 524 patients receiving intervention, and 461 receiving usual care, were analysed for efficacy. After 6 months, mean predicted risks were 12.5% with intervention, and 13.7% with usual care [odds ratio = 0.896; p = 0.001, adjusted for risk at baseline (17.2% intervention; 16.9% usual care) and other covariates]. The proportion of patients achieving both blood pressure and low-density lipoprotein cholesterol targets was significantly higher with intervention (25.4%) than usual care (14.1%; p < 0.001), and 29.3% of smokers in the intervention group quit smoking vs. 21.4% of those receiving usual care (p = 0.04). CONCLUSIONS: A physician-implemented CHD risk evaluation/communication programme improved patients' modifiable risk factor profile, and lowered predicted CHD risk compared with usual care. By combining this strategy with more intensive treatment to reduce residual modifiable risk, we believe that substantial improvements in cardiovascular disease prevention could be achieved in clinical practice.

Association of angiotensinogen M235T and A(-6)G gene polymorphisms with coronary heart disease with independence of essential hypertension: the PROCAGENE study. Prospective Cardiac Gene.

OBJECTIVES: We examined the relationship between the angiotensinogen (AGT) gene M235T polymorphism, the variant promoter of the AGT gene A(-6)G and the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and coronary heart disease (CHD) in native Gran Canaria Island habitants, who have the highest rates of CHD in Spain. BACKGROUND: Some studies subject that the ACE (I/D) polymorphism could be associated with CHD, while AGT (M235T) has been related to essential hypertension. METHODS: We studied 304 subjects with angiographic evidence of coronary artery disease and a clinical diagnosis of myocardial infarction or unstable angina and 315 age- and gender-matched controls. Blood was drawn and DNA extracted. Angiotensin-converting enzyme (I/D) gene polymorphism was analyzed by polymerase chain reaction (PCR) and AGT gene polymorphisms by restriction fragment length polymorphism-PCR and mutagenically-separated PCR. RESULTS: The ACE (I/D) polymorphism showed no association with CHD, whereas the frequency distribution of AGT (M235T) genotypes among patients and controls (235T: 29.1% and 19.0%; M235T: 48.5% and 50.2%; M235: 22.4% and 30.8%, respectively) was statistically different (p = 0.005) and not related to the presence of essential hypertension. Similar results were observed with the AGT A(-6)G polymorphism. In multiple logistic regression analysis, CHD odds ratio associated with 235T and M235 homozygotes were 1.7 (1.1 to 2.6) and 0.54 (0.36 to 0.82), respectively. CONCLUSIONS: This study shows that genetic variation of the AGT (M235T), but not the ACE (I/D), genotypes contributes to the presence of CHD independently of blood pressure profile in a subset of the Spanish population with a high prevalence of cardiovascular disease.

Comparison of the efficacy of dihydropyridine calcium channel blockers in African American patients with hypertension. ISHIB Investigators Group. International Society on Hypertension in Blacks.

BACKGROUND: Hypertension is a prevalent disease among African Americans, and successful treatment rates are low. Since calcium channel blockers are well-tolerated and efficacious in African Americans, we undertook this study to compare the efficacy, safety, and tolerability of 3 commonly prescribed calcium channel blockers: amlodipine besylate (Norvasc), nifedipine coat core (CC) (Adalat CC), and nifedipine gastrointestinal therapeutic system (GITS) (Procardia XL). METHODS: One hundred ninety-two hypertensive patients across 10 study centers were randomly assigned to double-blind monotherapy with amlodipine besylate (5 mg/d), nifedipine CC (30 mg/d), or nifedipine GITS (30 mg/d) for 8 weeks. Patients not achieving therapeutic response after 4 weeks had their dose doubled for the next 4 weeks. The primary end point was a comparison of the average reduction (week 8 minus baseline) in 24-hour ambulatory diastolic blood pressure (DBP). Secondary end points included a comparison of average 24-hour ambulatory systolic blood pressure (SBP), office SBP or DBP reduction, responder rates, safety, and tolerability. RESULTS: One hundred sixty-three patients were evaluable for efficacy after 8 weeks. There was no significant difference in the average 24-hour ambulatory DBP (-8.5, -9.0, and -6.1 mm Hg, respectively) or SBP (-14.3, -15.7, and -11.8 mm Hg, respectively) reduction. Average office SBP and DBP were reduced to a comparable degree (19-22 mm Hg [P =.50] and 12-14 mm Hg [P =.51], respectively). Responder rates (DBP <90 or reduced by > or = 10 mm Hg) were similar (P = .38). Discontinuation rates and adverse event frequency were distributed similarly across the 3 treatment groups. CONCLUSION: The efficacy, safety, and tolerability of the 3 dihydropyridine calcium channel blockers are equivalent in African Americans with stages 1 and 2 hypertension.

The rapidity of drug dose escalation influences blood pressure response and adverse effects burden in patients with hypertension: the Quinapril Titration Interval Management Evaluation (ATIME) Study. ATIME Research Group.

BACKGROUND: Antihypertensive medication doses are typically increased within several weeks after initiation of therapy because of inadequate blood pressure (BP) control and/or adverse effects. METHODS: We conducted a parallel-group clinical trial with 2935 subjects (53% women, n=1547) aged 21 to 75 years, with Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VI stages 1 to 2 hypertension, recruited from 365 physician practices in the southeastern United States. Participants were randomized either to a fast (every 2 weeks; n=1727) or slow (every 6 weeks; n=1208) drug titration. Therapy with quinapril, an angiotensin-converting enzyme inhibitor, was initiated at 20 mg once daily. The dose was doubled at the next 2 clinic visits until the BP was lower than 140/90 mm Hg or a dose of 80 mg was reached. RESULTS: Pretreatment BP averaged 152/95 mm Hg. Patients with stage 2 hypertension reported more symptoms than those with stage 1. The BP averaged 140/86, 137/84, and 134/83 mm Hg in the slow group compared with 141/88, 137/85, and 135/84 mm Hg in the fast group at the 3 respective clinic visits. The BP control rates to lower than 140/90 mm Hg at the 3 clinic visits were (slow, fast, respectively) 41.3%, 35.7% (P<.001); 54.3%, 51.5% (P=.16); and 68%, 62.3% (P=.02). In the fast group, 10.7% of participants experienced adverse events vs 10.8% in the slow group; however, 21.0% of adverse events in the fast group were "serious" vs only 12% in the slow group. CONCLUSION: Slower dose escalation of the angiotensin-converting enzyme inhibitor quinapril provides higher BP control rates and fewer serious adverse events than more rapid drug dose escalation.

Postural hypotension and postural dizziness in elderly women. The study of osteoporotic fractures. The Study of Osteoporotic Fractures Research Group.

BACKGROUND: Postural hypotension and dizziness are common findings in elderly individuals. Although postural hypotension and postural dizziness are often perceived to be strongly associated entities, evidence to support this view in sparse. In addition, there is a lack of knowledge regarding the relationship of postural hypotension and postural dizziness to potential clinical outcomes, such as falls, syncope, and restricted activity. METHODS: We utilized a cross-sectional examination to study the prevalence and correlates of postural hypotension (drop in systolic blood pressure of greater than or equal to 20 mm Hg after 1 minute of standing) and postural dizziness (self-reported dizziness on standing) in 9704 nonblack, ambulatory women aged 65 years and older enrolled in the multicenter Study of Osteoporotic Fractures. First, we examined postural hypotension and postural dizziness as outcomes of risk factors that included medical conditions, medications, and physical findings. Then, we examined falls, syncope, and impaired functional status as outcomes of postural hypotension and postural dizziness. RESULTS: Postural hypotension and postural dizziness were common findings, noted in 14% and 19% of subjects, respectively. However, they were not highly correlated with each other and did not share the same risk factors or associated outcomes. Postural dizziness was more strongly associated than was postural hypotension with history of falling (age-adjusted odds ratios, 1.32 vs 1.02), history of syncope (1.94 vs 1.35), and impaired functional status (1.95 vs 0.76). CONCLUSION: Assessment of dizziness on standing appears to be more important than measurement of postural blood pressure change in ascertaining functional status and risk of falls and syncope in elderly individuals. Future prospective studies of postural dizziness are needed to confirm its value as a predictor of clinical outcomes.

Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS)

Problems with sexual function have been a long-standing concern in the treatment of hypertension and may influence the choice of treatment regimens and decisions to discontinue drugs. The Treatment of Mild Hypertension Study (TOMHS) provides an excellent opportunity for examination of sexual function and effects of treatment on sexual function in men and women with stage I diastolic hypertension because of the number of drug classes studied, the double-blind study design, and the long-term follow-up. TOMHS was a double-blind, randomized controlled trial of 902 hypertensive individuals (557 men, 345 women), aged 45 to 69 years, treated with placebo or one of five active drugs (acebutolol, amlodipine maleate, chlorthalidone, doxazosin maleate, or enalapril maleate). All participants received intensive lifestyle counseling regarding weight loss, dietary sodium reduction, alcohol reduction (for current drinkers), and increased physical activity. Sexual function was ascertained by physician interviews at baseline and annually during follow-up. At baseline, 14.4% of men and 4.9% of women reported a problems with sexual function. In men, 12.2% had problems obtaining and/or maintaining an erection; 2.0% of women reported a problem having an orgasm. Erection problems in men at baseline were positively related to age, systolic pressure, and previous antihypertensive drug use. The incidences of erection dysfunction during follow-up in men were 9.5% and 14.7% through 24 and 48 months, respectively, and were related to type of antihypertensive therapy. Participants randomized to chlorthalidone reported a significantly higher incidence of erection problems through 24 months than participants randomized to placebo (17.1% versus 8.1%, P = .025). Incidence rates through 48 months were more similar among treatment groups than at 24 months, with nonsignificant differences between the chlorthalidone and placebo groups. Incidence was lowest in the doxazosin group but was not significantly different from the placebo group. Incidence for acebutolol, amlodipine, and enalapril groups was similar to that in the placebo group. In many cases, erection dysfunction did not require withdrawal of medication. Disappearance of erection problems among men with problems at baseline was common in all groups but greatest in the doxazosin group. Incidence of reported sexual problems in women was low in all treatment groups. In conclusion, long-term incidence of erection problems in treated hypertensive men is relatively low but is higher with chlorthalidone treatment. Effects of erection dysfunction with chlorthalidone appear relatively early and are often tolerable, and new occurrences after 2 years are unlikely. The rate of reported sexual problems in hypertensive women is low and does not appear to differ by type of drug. Similar incidence rates of erection dysfunction in placebo and most active drug groups caution against routine attribution of erection problems to antihypertensive medication.

Role of left ventricular hypertrophy in diastolic dysfunction in aged hypertensive patients.

OBJECTIVE: To evaluate the influence of left ventricular hypertrophy (LVH) on the diastolic dysfunction in older hypertensive patients. METHODS: In total 665 patients (58% men, 61% White, aged 55-80 years) with mild-to-moderate essential hypertension underwent Doppler echocardiography. Data included left ventricular dimensions, left ventricular mass index, body mass index, E- and A-wave mitral flow velocities, E:A ratio, deceleration time > 150 ms), impaired relaxation (E:A ratio < 1.0, prolonged deceleration time according to age), and restrictive physiology (E:A ratio > 2.1, deceleration time < 150 ms)]. Data were distributed according to age (50-59, 60-69, and 70-80 years). RESULTS: The overall prevalence of sex-adjusted LVH in this study was 65%. When we compared hypertensive patients with and without LVH, the E- and A-wave velocities, E:A ratio, and deceleration time were similar. Moreover, the prevalences of normal, impaired relaxation, and restrictive physiology patterns among patients with and without LVH did not differ significantly (20, 79.5, and 0.5 versus 24, 75.5, and 0.5%). When the mitral flow patterns were adjusted according to age, the impaired relaxation pattern increased further with age (to 73% during the fifth decade, 83% during the sixth decade, and 88% during the seventh decade). CONCLUSIONS: LVH is not an independent factor associated with abnormal flow patterns in hypertensive patients aged over 50 years with normal systolic contractility. The impaired relaxation is the predominant pattern of diastolic dysfunction in older hypertensive patients and increases further with aging.

Inhibition of platelet aggregability by losartan in essential hypertension.

Most clinical events associated with hypertension have a thrombotic component. Losartan is a selective, competitive antagonist of the thromboxane A2 receptor in experiments performed in isolated vascular strips and in human and rat platelet-enriched plasma. In this study, we investigated for the first time whether losartan at therapeutic doses has an effect on platelet aggregability and indexes of fibrinolysis in essential hypertensive subjects. Changes in the dose-response curve to platelet aggregation induced by the thrombin receptor-activating peptide SFLRRN-NH2 were determined in 9 patients (56% men, 72% white; mean age 52.8 years) with stage I or II essential hypertension and in 9 untreated healthy volunteers. After a 4-week washout period, hypertensive subjects received 2 weeks of placebo followed by 4 weeks of losartan 50 mg/day. Both subjects and end points were blinded for treatment assignment. In addition, plasminogen activator inhibitor type 1 antigen and von Willebrand antigen were studied in all patients and controls. Four weeks of losartan produced a statistically significant (p <0.05) increase in the concentration of SFLRRN-NH2 required to induce a half-maximal response in platelet aggregation extent and rate 4 weeks after initiation of treatment. The decrease in platelet aggregability was independent of blood pressure control and the effects of gender and age. Losartan had no effect on plasma concentrations of plasminogen activator inhibitor-1 and von Willebrand factor in hypertensive subjects. These data demonstrate for the first time a novel antiplatelet effect of losartan at therapeutic doses, which was independent of changes in blood pressure, plasma markers of fibrinolytic activity, and endothelial perturbation.

Disparity between diastolic mitral flow characteristics and left ventricular mass in essential hypertension.

Because left ventricular (LV) hypertrophy and aging have been associated with abnormal LV relaxation, this study evaluated the impact of LV mass on the filling patterns derived by Doppler in a large population aged > or =50 years. Results suggest that in essential hypertension the intrinsic myocardial composition is more important than cardiac hypertrophy in determining LV diastolic properties. This apparent discrepancy between LV mass and diastolic filling patterns highlights the difficulty in establishing the diagnosis of diastolic dysfunction in elderly hypertensives.

Impact of ethnicity on left ventricular mass and relative wall thickness in essential hypertension.

This study was designed to evaluate the impact of ethnicity on left ventricular (LV) mass, and relative wall thickness in 527 patients (57% men, mean age 60 +/- 7 years) with mild to moderate high blood pressure. There were 63% Caucasians, 21% African-Americans, and 16% Hispanics. LV mass was indexed according to body surface area, height, and height to the allometric power of 2.7. Relative wall thickness included the 4 widely recognized patterns: normal, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. LV mass indexed to body surface area was similar among all 3 ethnic groups (Caucasians 117.1 g/m2, African-Americans 119.2 g/m2, Hispanics 122.7 g/m2); however, when indexed to height and height to the power of 2.7, Hispanics had slightly larger masses than the other 2 groups (Hispanics 168.1 and 73.3 g/m2.7 vs Caucasians 159.8 and 64.4 g/m2.7 [p = NS and p < 0.005]; and vs African-Americans 164.8 and 69.2 g/m2.7 [p = NS for both]). Using body surface area, the concentric remodeling was the predominant form of cardiac adaptation in Caucasians (36%) and African-Americans (42%), whereas the concentric hypertrophy pattern was 38% in Hispanics. Using indexing for both height and height to the power of 2.7, the concentric hypertrophy pattern predominated in all 3 ethnic groups (Caucasians 48% and 51%; African-Americans 68% and 66%; Hispanics 59% and 65%). In conclusion, because of the independent impact of weight on high blood pressure, LV mass adjusted to height or to height at the power of 2.7 should be reported in population studies. The concentric hypertrophy pattern--classic LV response to pressure overload conditions--is better represented when LV mass is indexed to height or to height to the allometric power of 2.7 than to body surface area.

Gender dimorphism in cardiac adaptation to hypertension is unveiled by prior treatment and efficacy.

The gender dimorphism in cardiac remodeling, previously recognized in primary hypertension, is unveiled in the group of patients with uncontrolled hypertension despite medical therapy. Prior antihypertensive treatment and its efficacy should be considered in population studies designed to evaluate the impact of left ventricular hypertrophy or its regression.

Comparison of left ventricular mass and geometric remodeling in treated and untreated men and women >50 years of age with systemic hypertension.

To investigate the effects of left ventricular (LV) mass and geometry in hypertensive patients >50 years of age, 540 men and women were divided into controlled, uncontrolled, and untreated groups. The high prevalence of concentric LV hypertrophy in postmenopausal women, despite medical therapy, emerged as a potentially important and underrecognized factor of their cardiovascular risk.

Comparison in systemic hypertension of left ventricular mass and geometry with systolic and diastolic function in patients <65 to > or = 65 years of age.

Previous studies have differed on the independent effect of age and gender to left ventricular (LV) mass. Data on ventricular remodeling in hypertensive patients > or = 65 years of age is lacking. Similarly, the systolic and diastolic interaction in older hypertensives is not well defined. In a prospective study, we examined the relation of LV mass, relative wall thickness, and systolic and diastolic interaction in 508 hypertensive patients between 50 and 80 years of age who were divided according to age (<65 and > or = 65 years) and gender. LV mass, geometric classification, systolic wall stress, and Doppler filling were obtained according to standard Doppler echocardiographic criteria. In men, most measurements were similarly distributed. However, women > or = 65 years of age had smaller LV systolic dimensions, thicker ventricular septums, higher endocardial and midwall fractional shortenings, and lower end-systolic wall stress. Although LV mass was higher in men, there was no age difference within the same sex. The most common LV geometric remodeling was increased relative wall thickness in the form of concentric hypertrophy or concentric remodeled. The predominant mitral flow pattern was "impaired relaxation"; however, older patients had even shorter E waves, taller A waves, and lower E/A ratios. Thus, patients > or = 65 years of age had an even higher prevalence of this pattern (men, 89% vs 73%, p <0.001, and women, 91% vs 77%, p <0.001). Delayed LV relaxation with preservation of systolic ejection indexes is an early abnormality in essential hypertension, which lasts an undetermined time with further progression as patients aged. As a result, hypertensive patients > or = 65 years of age had the most pronounced structural and functional changes, an observation particularly noted in women. In those > or = 65 years, data from the Doppler E wave and A wave do not distinguish the physiologic process of aging from the pathologic changes of pressure overload.

Correlates of impaired function in older women.

OBJECTIVE: To determine the factors associated with impaired function in older women. DESIGN: Cross-sectional analysis of baseline data collected for a multicenter, prospective study of risk factors for osteoporotic fractures. SETTING: Four clinical centers in Portland, Oregon, Minneapolis, Minnesota, Baltimore, Maryland, and the Monongahela Valley, Pennsylvania. PARTICIPANTS: A total of 9,704 ambulatory, non-black women, aged 65 years and older, recruited from population-based listings. MEASUREMENTS: Independent variables, including demographic and historical information (medical conditions, health habits, and medications) and physiologic measures (anthropometry, blood pressure, mental status, vision, and neuromuscular performance) were obtained from a baseline questionnaire, interview, and examination. Measurement of function was assessed by self-reported ability to perform six physical and instrumental activities of daily living (ADL) and impaired function (dependent variable) was defined as difficulty performing three or more physical and instrumental ADLs. RESULTS: In order of decreasing strength of association, hip fracture, osteoarthritis, parkinsonism, slower walking speed, lower hip abduction force, back pain, greater Quetelet index, osteoporosis, former alcohol use, stroke, never drinking alcohol, lower mental status, use of anxiolytics and/or sleeping medications, inability to hold the tandem position, postural dizziness, cataracts, greater waist to hip ratio, lower physical activity in the past year, greater lifetime cigarette consumption, and lower grip strength were independently associated with impaired function in multivariate analyses. Age, low educational level, diabetes, current heavy alcohol use, postural hypotension, depth perception, and contrast sensitivity were not independent predictors. A combination of neuromuscular performance measures, including decreased muscle strength and impaired balance and gait, appeared to account for the effect of age on disability. CONCLUSION: A combination of many factors, including medical conditions, health habits such as obesity, smoking, alcohol abstinence, and physical inactivity, and direct measures of neuromuscular performance are associated with impaired function in older women.

Characterization of angiotensin-(1-7) in the urine of normal and essential hypertensive subjects.

A total of 31 healthy volunteers [39 +/- 7 (SD) years] and 18 untreated essential hypertensive subjects [43 +/- 9 years] collected urine for 24 h after a physical examination and laboratory tests. Radioimmunoassay measurements of angiotensin-(1-7) [Ang-(1-7)] in urine and plasma were done as described previously. Sitting systolic and diastolic blood pressures (+/- SD) averaged 118 +/- 11/74 +/- 7 mm Hg and 146 +/- 16/96 +/- 8 mm Hg in normal and essential hypertensive subjects, respectively (P < .001), whereas 24 h urinary volume was not different in normal and essential hypertensive subjects (P > .05). The concentration of Ang-(1-7) in the urine of normal subjects averaged 62.6 +/- 22.6 pmol/L corresponding to a urinary excretion rate of 98.9 +/- 44.7 pmol/24 h. Concurrent measurements of plasma Ang-(1-7) showed that the content of Ang-(1-7) in urine was 2.5-fold higher than that measured in the plasma. In contrast, untreated essential hypertensive subjects had lower concentrations and 24 h urinary excretion rates of Ang-(1-7) averaging 39.4 +/- 18.0 pmol/L and 60.2 +/- 14.6 pmol/24 h, respectively, (P < .001). Differences in the excretory rate of Ang-(1-7) between normal volunteers and essential hypertensive subjects were not modified by normalization of the data by urinary creatinine excretion rates. Urinary concentrations of Ang-(1-7) correlated inversely with systolic, diastolic and mean arterial pressures (r = -0.48, P < .001). Both urinary Ang-(1-7) [odds ratio of 0.92 (95% CI: 0.88-0.97)] and age were independent predictors of systolic blood pressure. These studies demonstrated the presence of Ang-(1-7) in urine and the existence of reduced levels of the heptapeptide in individuals with untreated essential hypertension. The relatively higher concentrations of Ang-(1-7) in urine compared to plasma agrees with data that showed that Ang-(1-7) may contribute to the regulation of blood pressure. The inverse association between Ang-(1-7) and arterial pressure provides a potential marker for the characterization of forms of essential hypertension associated with reduced production or activity of vasodilator hormones.

Differential actions of angiotensin-(1-7) in the kidney.

Angiotensin-(1-7) is a bioactive component of the renin-angiotensin system that is endogenously formed in the circulation and various tissues by several enzymatic pathways from either angiotensin (Ang) I or Ang II. Initial studies indicated that Ang-(1-7) mimicked some of the effects of Ang II, including stimulation of release of prostanoids and vasopressin. However, Ang-(1-7) is devoid of the vasoconstrictor, central pressor, or thirst-stimulating actions associated with Ang II. In fact, new findings reveal depressor, vasodilator, and antihypertensive actions that may be more apparent in hypertensive animals or humans. Thus, increasing evidence suggests that Ang-(1-7) may oppose the actions of Ang II directly or as a result of increasing prostaglandins or nitric oxide. In this review, we examine recent studies to address whether the kidney is a target organ for antihypertensive actions of Ang-(1-7).

Therapeutic implications of the epidemiology and timing of myocardial infarction and other cardiovascular diseases.

Cardiovascular diseases (CVD) account for almost 50% of the 2 million deaths annually in the United States. Coronary heart disease (CHD) (ie, myocardial infarction, sudden death) account for the largest proportion (32%) of this mortality. Over the last 3 decades both CVD and age-adjusted coronary death rates have fallen dramatically. However, crude CVD (and CHD) incidence is actually increasing, almost exclusively as a function of rising CVD incidence amongst older Americans. Population groups at highest for premature CVD complications include African-Americans, diabetics, men, smokers, and those with high levels of single risk factors (ie, stage III hypertension). Individuals with multiple CVD risk factors as well as those with manifestations of blood pressure (BP)-related target-organ damage (TOD) (ie, left ventricular hypertrophy, hypercreatinemia) are at an inordinately high risk for clinical events. CVD events do not randomly occur throughout the 24-h time period. The peak incidence of myocardial infarction (MI), thrombotic stroke, sudden cardiac death, and transient myocardial ischemia is between 6 am and 12 noon. During the morning hours coinciding with the peak incidence of CVD events, coronary vasomotor tone, plasma catecholamines, and platelet aggregability are at their highest levels while coronary blood flow and plasma fibrinolytic activity are at their lowest levels of the day. Moreover, BP rapidly rises from its nocturnal nadir during the early morning hours. Prevention of pressure-related CVD events in hypertensive patients over the long term can be best accomplished by controlling BP throughout the 24 h time period with drugs that do not adversely impact (or favorably affect) other metabolic, neurohormonal, and hemostatic parameters. BP control (minimally to <140/90 mm Hg) may be particularly important in the early morning hours since elevated BP and/or rapidly rising BP is a plausible biological trigger for the aforementioned CVD events. One effective strategy for achieving this goal is to utilize antihypertensive drugs with long therapeutic half-lives. Such agents will provide smooth whole-day BP control and also will minimize the loss of BP control during time period(s) between missed medication doses in the setting of therapeutic non-compliance. Practitioners should give due consideration to nocturnal administration of antihypertensive drugs prescribed once-daily as a means of achieving more effective morning BP control.

Status of health and prevalence of hypertension in Brazil.

In the last 40 years Brazil has experienced both a demographic and an epidemiological transition. Life expectancy has increased and fertility rates have declined. Cardiovascular disease (CVD) has become the leading cause of death, as infectious disease incidence declined. Hypertension is the leading reason for disability benefits and a key factor for cardiovascular disease morbidity and mortality. Hypertension prevalence in Brazil ranges from 5% to 40%, depending on the region of the country and the population subgroup. Risk factors for hypertension are older age, higher body mass index, black ethnicity, high salt and alcohol intake, acculturation of native populations, and additionally, for women, oral contraceptive use. Although there are nationally issued guidelines for hypertension treatment, outcome studies evaluating such programs are scarce. Information available from selected populations suggest that hypertension awareness, treatment and control rates are very low. There is a need for development and implementation of primary prevention programs with adequate evaluation mechanisms to reduce the burden of the disease in the years to come.

Oral contraceptive use and blood pressure levels among women workers in São Paulo, Brazil.

Oral contraceptive use has been increasing in Brazil since the late 1970s, and oral contraceptives have been associated with higher incidence of cardiovascular diseases, including hypertension, since their release in the United States and Europe. We examined the association between oral contraceptive use and blood pressure levels in 1457 workers from 10 sectors of the economy, between the ages of 15 and 49 years, in São Paulo, Brazil. Oral contraceptive use was associated with higher age, lower parity, higher income, white ethnic group, and administrative occupations. Using multiple linear regression and logistic regression techniques, we evaluated blood pressure and hypertension differences between users and nonusers. Oral contraceptive users had a mean systolic blood pressure 2.6 mm Hg higher than nonusers after adjustment for multiple potential confounders, including age, income, parity, ethnicity, body mass index, and occupation. There was a statistically significant positive trend between length of time on oral contraceptives and mean systolic blood pressure levels. After adjustment for demographic and social variables, there were no differences between whites and blacks. Oral contraceptive users have an adjusted odds ratio for hypertension of 2.66 (95% CI: 1.51-4.70). The finding of an increasingly positive association between oral contraceptive use and mean systolic blood pressure level suggests cause and effect. This observation has substantial importance because systolic blood pressure is considered the primary predictor of blood pressure-associated morbidity and mortality. This may pose a particular problem in Brazil, since most women on oral contraceptives are not under medical supervision.