The influence of physical activity on vascular complications and mortality in patients with type 2 diabetes mellitus.

AIMS: There is limited evidence regarding the association between physical activity and vascular complications, particularly microvascular disease, in patients with type 2 diabetes. METHODS: From the 11 140 patients in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial, the effect of physical activity, categorized as none, mild, moderate or vigorous, and the number of sessions within a week, was examined in multivariable regression models adjusted for potential confounders. The study end-points were major cardiovascular events, microvascular complications and all-cause mortality. RESULTS: Forty-six percent of participants reported undertaking moderate to vigorous physical activity for >15 min at least once in the previous week. During a median of 5 years of follow-up, 1031 patients died, 1147 experienced a major cardiovascular event and 1136 a microvascular event. Compared to patients who undertook no or mild physical activity, those reporting moderate to vigorous activity had a decreased risk of cardiovascular events (HR: 0.78, 95% CI: 0.69-0.88, p < 0.0001), microvascular events (HR: 0.85, 95% CI: 0.76-0.96, p = 0.010) and all-cause mortality (HR: 0.83, 95% CI: 0.73-0.94, p = 0.0044). CONCLUSIONS: Moderate to vigorous, but not mild, physical activity is associated with a reduced incidence of cardiovascular events, microvascular complications and all-cause mortality in patients with type 2 diabetes.

Resting heart rate and the risk of death and cardiovascular complications in patients with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: An association between resting heart rate and mortality has been described in the general population and in patients with cardiovascular disease. There are, however, few data exploring this relationship in patients with type 2 diabetes mellitus. The current study addresses this issue. METHODS: The relationship between baseline resting heart rate and all-cause mortality, cardiovascular death and major cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) was examined in 11,140 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Study. RESULTS: A higher resting heart rate was associated with a significantly increased risk of all-cause mortality (fully adjusted HR 1.15 per 10 bpm [95% CI 1.08, 1.21], p<0.001), cardiovascular death and major cardiovascular outcomes without adjustment and after adjusting for age and sex and multiple covariates. The increased risk associated with a higher baseline resting heart rate was most obvious in patients with previous macrovascular complications (fully adjusted HR for death 1.79 for upper [mean 91 bpm] vs lowest [mean 58 bpm] fifth of resting heart rate in this subgroup [95% CI 1.28, 2.50], p = .001). CONCLUSIONS/INTERPRETATION: Among patients with type 2 diabetes, a higher resting heart rate is associated with an increased risk of death and cardiovascular complications. It remains unclear whether a higher heart rate directly mediates the increased risk or is a marker for other factors that determine a poor outcome.

Metabolic syndrome, impaired fasting glucose and obesity, as predictors of incident diabetes in 14 120 hypertensive patients of ASCOT-BPLA: comparison of their relative predictability using a novel approach.

AIMS: To evaluate, in hypertensive patients, whether the metabolic syndrome is a better predictor of new-onset diabetes compared with impaired fasting glucose, obesity or its other individual components alone, or collectively. METHODS: Cox models were developed to assess the risk of new-onset diabetes associated with the metabolic syndrome after adjusting for a priori confounders (age, sex, ethnicity and concomitant use of non-cardiovascular medications), its individual components and other determinants of new-onset diabetes. Area under receiver operator curves using the metabolic syndrome or models of impaired fasting glucose were compared, and the ability of these models to correctly identify those who (after 5-years of follow-up) would or would not develop diabetes was assessed. RESULTS: The metabolic syndrome adjusted for a priori confounders and its individual components, and further adjusted for other determinants, was associated with significantly increased risk of new-onset diabetes [1.19 (1.00-1.40), P = 0.05 and 1.22 (1.03-1.44), P = 0.02, respectively]. The discriminative ability of the metabolic syndrome model [area under receiver operating curve: 0.764 (0.750-0.778)] was significantly better than the model of impaired fasting glucose [0.742 (0.727-0.757)] (P < 0.001). The metabolic syndrome correctly allocates the risk of new-onset diabetes in a significantly higher proportion of patients (62.3%) than impaired fasting glucose status (37.7%) (P < 0.001). The presence of both the metabolic syndrome and impaired fasting glucose were associated with an approximately 9-fold (7.47-10.45) increased risk of new-onset diabetes. Among normoglycaemic patients, the metabolic syndrome was also associated with significantly increased risk of new-onset diabetes, after adjusting for BMI and a priori confounders [1.66 (1.29-2.13)]. CONCLUSIONS: Both impaired fasting glucose and the metabolic syndrome predict the risk of new-onset diabetes; however, the metabolic syndrome is a better predictor than impaired fasting glucose in assigning the risk of new-onset diabetes in hypertensive patients, and among those with normoglycaemia.

The economic consequences of non-adherence to lipid-lowering therapy: results from the Anglo-Scandinavian-Cardiac Outcomes Trial.

BACKGROUND: Adherence to lipid-lowering therapy in clinical practice is less than ideal. Analysis of registry data has indicated that this is associated with poor outcomes. The objective of the present analysis was to assess the impact of high adherence to drug (defined as > 80% of days covered), compared with low adherence to drug (< 50% of days covered) in terms of risk of events and long-term economic consequences. DESIGN: Open-label follow up of a randomised placebo-controlled trial in hypertensive patients. METHODS: Cox proportional hazards and Poisson regression models were used to assess the hazard ratio of patients with high adherence compared with low adherence while controlling for cardiovascular risk. A Markov model was used to predict the long-term costs and health outcomes associated with poor adherence during the follow-up period. RESULTS: Both statistical models indicated that high adherence is associated with improved prognosis [Cox model: 0.75; 95% confidence interval (CI): 0.56-0.98, Poisson model hazard ratio: 0.73; 95% CI: 0.58-0.98]. Discounted at 3.5% per year, the Markov model predicts that as a consequence of higher adherence during the follow-up period, costs would be higher (1689 pounds per patient compared with 1323 pounds per patient) because of higher drug costs, but the projected survival and quality-adjusted survival (QALY) would also be longer (10.83 compared with 10.81 life years and 8.13 compared with 8.11 QALYs). CONCLUSION: Given the higher risk of cardiovascular events associated with low adherence shown here, measures to improve adherence are an important part of the prevention of cardiovascular disease.

Effects of HIV status and antiretroviral therapy on blood pressure.

OBJECTIVE: High blood pressure is a major risk factor for cardiovascular disease and concerns have been raised over its possible association with antiretroviral drugs. The objective of this study was to explore the associations among blood pressure, HIV status and two predefined highly active antiretroviral therapy (HAART) regimens: treatment with and without nonnucleoside reverse transcriptase inhibitors (NNRTIs) (NNRTI- and non-NNRTI-based HAART). METHOD: A cross-sectional survey was conducted among 612 adults attending the Sexual Health Outpatient Department at St Mary's NHS Hospital Trust, London. RESULTS: HIV-infected patients treated with NNRTIs had a blood pressure that was 4.6/4.2 mmHg higher than those who were HIV positive but treatment naïve. The diastolic difference remained statistically significant after adjusting for potential confounders of this association (2.4 mmHg; P=0.03). There was no difference in blood pressure between those treated with non-NNRTI-based regimens and those who were HIV positive but treatment naïve. CONCLUSION: NNRTIs may be associated with an increase in blood pressure. Pending further more robust evidence from randomized clinical trials it would be prudent for clinicians to monitor blood pressure in all HIV-infected patients, particularly after initiating treatment with NNRTIs, and to commence antihypertensive therapy whenever appropriate.

The effects of antihypertensive therapy on carotid vascular structure in man.

OBJECTIVE: An increased carotid intima-media thickness (IMT) has been found to be associated with a number of cardiovascular risk factors such as age, hypertension, cigarette smoking, hypercholesterolaemia and left ventricular hypertrophy. Our objective was to assess whether carotid intima-media thickness in hypertensive patients could be reduced by antihypertensive therapy. METHODS: 13 hypertensive patients, 10 previously untreated, were examined using carotid ultrasonography and echocardiography at baseline and then at 8 weeks and 39 weeks after commencement of antihypertensive therapy with ramipril and the second-line addition of felodipine. RESULTS: By the end of the study significant regression of IMT (0.1(0.05-0.16) mm, F-value 10.2, P < 0.01) and left ventricular mass index had occurred (25(10.7-39.3) g/m2, F-value 9.7, P < 0.01). The reduction in IMT was significantly related to the reduction in mean arterial pressure, r = 0.55, P = 0.05). CONCLUSION: Antihypertensive therapy with ramipril and felodipine causes regression of IMT in hypertensive patients, probably chiefly through blood pressure reduction. Large prospective studies are required to assess whether a reduction in IMT results in a reduction in morbidity and mortality.

Left ventricular hypertrophy and QT dispersion in hypertension.

The interlead variation in QT length on a standard electrocardiograph reflects regional repolarization differences in the heart. To investigate the association between this interlead variation (QT dispersion) and left ventricular hypertrophy, we subjected 100 untreated subjects to 12-lead electrocardiography and echocardiography. Additionally, 24 previously untreated subjects underwent a 6-month treatment study with ramipril and felodipine. In the cross-sectional part of the study, QT dispersion corrected for heart rate (QTc dispersion) was significantly correlated with left ventricular mass index (r = .30, P < .01), systolic pressure (r = .30, P < .01), the ratio of peak flow velocity of the early filling wave to peak flow velocity of the atrial wave (E/A ratio) (r = -.22, P = .02), isovolumic relaxation time (r = .31, P < .01), and age (r = .21, P < .04). In the treatment part of the study, lead-adjusted QTc dispersion decreased from 24 to 19 milliseconds after treatment, and after a subsequent 2 weeks of drug washout remained at 19 milliseconds (P < .01). The changes in left ventricular mass index at these stages were 144, 121, and 124 g/m2 (P < .01). Systolic pressure decreased from 175 to 144 mm Hg and increased again to 164 mm Hg after drug washout (P < .01). The E/A ratio (0.97, 1.02, and 1.02; P = 69) and isovolumic relaxation time (111, 112, and 112; P = .97) remained unchanged through the three assessment points. In conclusion, QT dispersion is increased in association with an increased left ventricular mass index in hypertensive individuals. Antihypertensive therapy with ramipril and felodipine reduced both parameters. If an increased QT dispersion is a predictor of sudden death in this group of individuals, then the importance of its reduction is evident.

Ethnic differences in the hypertensive heart and 24-hour blood pressure profile.

Black hypertensive persons have been observed to have a greater degree of left ventricular hypertrophy than white hypertensives. However, previous studies have matched groups for blood pressure (BP) measured in the clinic, and it has been demonstrated that black hypertensives have an attenuated nocturnal BP dip. Clinic BPs may thus underestimate mean 24-hour BP in this group. To investigate whether the differences in left ventricular hypertrophy can be accounted for by the greater mean 24-hour BP in black hypertensives, 92 previously untreated hypertensives were studied with 24-hour ambulatory BP monitoring and echocardiography. The 46 black hypertensives (24 men and 22 women) were matched with the 46 white hypertensives for age, gender, and mean 24-hour BP. Despite similar mean 24-hour BPs (blacks, 142/93 mm Hg; whites, 145/92 mm Hg; P=.53/.66), the black group had a smaller mean nocturnal dip than the white group (blacks, 8/8 mm Hg; whites, 16/13 mm Hg; P<.01). In addition, mean left ventricular mass index (LVMI) was greater (blacks, 130 g/m2; whites, 107 g/m2; P<.001). Mean 24-hour systolic BP was significantly related to LVMI in both groups (blacks, r=.45, P<.01; whites, r=.56, P<.01). However, systolic BP dip correlated inversely with LVMI only in the black group (blacks, r=-.30, P<.04; whites, r=.05, P=.76). In a multiple regression model, LVMI was independently related to both mean daytime BP and mean nocturnal BP dip in black subjects but only to mean daytime BP in white subjects. In conclusion, the increased left ventricular hypertrophy observed in black hypertensives compared with white hypertensives is not accounted for by differences in mean 24-hour BP. However, LVMI in black hypertensives appears to be more dependent on nocturnal BP than that in white hypertensives; this, coupled with the attenuated BP dip in black hypertensives, suggests that the BP profile rather than 24-hour BP may be important in determining the differences in left ventricular hypertrophy.

Medical education--communicating best practice.

There is unequivocal evidence that reduction of modifiable risk factors for coronary heart disease (CHD), such as elevated serum cholesterol, high blood pressure and smoking, decreases cardiovascular mortality. However, levels of intervention appear to be poor and there is often little evidence of a combined multiple risk factor approach to intervention, which is likely to be the optimal way to lower a patients overall risk of developing CHD. Attention has recently focused on bridging the gap between knowledge in the field of preventive cardiology and its application in everyday clinical practice. This can only be accomplished by the development of uncomplicated, practical guidelines that are evidenced-based and that provide specific targets for risk factors and indications for drug therapy.

Risk factors associated with the development of peripheral arterial disease in smokers: a case-control study.

PURPOSE AND METHOD: A hospital based case-control study was designed to investigate what aspects of smoking and what co-factors of smoking are associated with the development of peripheral arterial disease (PAD). Cases were 291 smokers, newly referred with PAD, and controls were 828 age and sex matched smokers without PAD. RESULTS: Reported recent tobacco usage was similar in cases and controls but total tobacco exposure was associated with the risk of PAD-adjusted odds ratios (ORs) increasing with tertile of pack-years smoked to reach 1.63 (95% CI, 1.11-2.39; P = 0.011), for the highest tertile ( > 48 pack-years) compared with smokers in the lowest tertile (< 31 pack-years). Cases reported smoking significantly lower tar and nicotine yield cigarettes than controls, but tended to inhale more deeply, and had significantly higher plasma concentrations of cotinine. ORs for PAD were significantly and independently increased by systolic blood pressure > 160 mmHg (8.1 (5.2 13.0); P < 0.0001), history of hypertension (2.4 (1.5-3.2); P = 0.0003) and apolipoprotein B > 0.9 g/l(3.8 (2.3-7.6); P = 0.008). CONCLUSIONS: Increased total exposure to tobacco and the ability to smoke tobacco in a way which maximises nicotine yield are associated with increased risk of smokers developing PAD. There is no evidence that smoking low tar cigarettes reduces this risk, whereas both hypertension (particularly systolic) and high levels of apolipoprotein B, increase this risk.

Blood pressure screening, management and control in England: results from the health survey for England 1994.

OBJECTIVE: To assess the current levels of awareness, treatment and control of hypertension in England and to determine the number and type of drugs prescribed. DESIGN: A cross-sectional household-based survey of English adults. SUBJECTS: A random sample from the adult English population of 12,116 adults who participated in the 1994 Health Survey for England. MAIN OUTCOME MEASURES: Prevalences of treatment hypertension, awareness and control. RESULTS: Using a definition of hypertension as a systolic blood pressure > or = 160 mmHg or a diastolic blood pressure > or = 95 mmHg, or a patient's being administered antihypertensive treatment, the prevalence of awareness of hypertension was 63%. Among hypertensives, 50% were receiving treatment and 30% had their hypertension controlled (< 160 mmHg/95 mmHg). Awareness, treatment and control rates are considerably lower than the most recently reported rates from the USA. Diuretics and beta-blockers remain the most common antihypertensive agents used in England. CONCLUSION: There is considerable scope for improving the treatment and control of hypertension in the English adult population.

Blood pressure in women using oral contraceptives: results from the Health Survey for England 1994.

OBJECTIVE: To assess whether the blood pressure is higher among women who take oral contraceptives than it is among those who do not. DESIGN: A cross-sectional survey of a stratified random sample of English adults (aged > or = 16 years). SETTING: Non-institutionalized households in England during 1994. PARTICIPANTS: From this sociodemographically representative sample of English adults, 3545 premenopausal women, of whom 892 were current users of oral contraceptives, were evaluated. INTERVENTIONS: An interviewer-administered questionnaire determined details of menopausal status, use of oral contraceptives and antihypertensive agents and other sociodemographic variables. Measurements of the weight, height and blood pressure (the mean of the last two of three readings taken with a Dinamap 8100 device) were recorded. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures adjusted for potential confounders by oral-contraceptive-user status. RESULTS: Mean blood pressures adjusted for age were significantly higher among oral contraceptive users (125/70 mmHg) than they were among non-users (123/68 mmHg, P < 0.001 both for systolic and for diastolic blood pressures). These results remained unchanged after further adjustment for the body mass index, alcohol intake, physical activity and hypertension treatment. Blood pressure differences tended to be larger among older oral contraceptive users. Oral contraceptives containing progestogen only were not associated with higher blood pressures. CONCLUSIONS: Despite the fact that most combined oral contraceptives in current use in England contain low doses of oestrogen, slightly but significantly higher blood pressures were observed among oral contraceptive users. Blood pressures should be screened before oral contraceptives are supplied and should be monitored regularly during oral contraceptive use.

PIP: The association between blood pressure and oral contraceptive (OC) use was investigated in 3545 randomly selected premenopausal women included in the 1994 Health Survey for England. 892 (25.2%) of these women were current OC users, 815 users of combined OCs and 77 of progestogen-only OCs. Age-adjusted mean diastolic and systolic blood pressure measurements were significantly higher among OC users (125/70 mmHg) than among non-users (123/68 mmHg) (p 0.001). This association remained significant even after adjustment for body mass index, alcohol consumption, physical activity, and hypertension treatment. Progestin-only OCs did not increase blood pressure, however. Finally, blood pressure differences between OC users and non-users tended to increase with age. Although the magnitude of the difference observed in the present study was small, these findings suggest that blood pressure should be checked before OCs are prescribed and monitored regularly throughout OC use. Women with hypertension who require OCs should be provided with progestogen-only formulations.

Ventricular arrhythmias in hypertension: in which patients do they occur?

OBJECTIVE: It has been suggested that the increased incidence of sudden death in hypertensive patients, particularly those with left ventricular hypertrophy, may be casually related to the increased number and complexity of ventricular arrhythmias that have been demonstrated in these patients. The objective of the present study was to assess some of the factors which might be responsible for these arrhythmias. SUBJECTS AND METHODS: One hundred and three untreated subjects were divided into four groups on the basis of blood pressure and echocardiographic measurements: hypertensive patients with left ventricular hypertrophy (n = 38), hypertensive patients without left ventricular hypertrophy (n = 16), patients with borderline or white-coat hypertension (n = 26) and normotensive subjects (n = 23). Each subject underwent two-dimensional and Doppler echocardiography, 12-lead electrocardiogram examination, 12-lead electrocardiogram exercise stress testing, 24-h ambulatory blood pressure monitoring and 24-h Holter monitoring. A further 17 hypertensive patients with left ventricular hypertrophy who were on long-term antihypertensive therapy were also investigated in the same manner and compared with untreated hypertensive patients with left ventricular hypertrophy who were matched for age, sex and race. RESULTS: Untreated hypertensive patients, even with left ventricular hypertrophy, had a low prevalence of frequent or complex arrhythmias (seven out of 80 patients with Lown score 2+). In contrast, hypertensive patients with left ventricular hypertrophy on long-term antihypertensive therapy had a significantly greater prevalence of complex arrhythmias than untreated patients with left ventricular hypertrophy (eight out of 17 treated patients compared with two out of 17 untreated patients with Lown score 2+). CONCLUSIONS: Hypertensive patients with left ventricular hypertrophy who had received long-term antihypertensive therapy were found to have a high prevalence of complex ventricular arrhythmias, which was in contrast to untreated hypertensive patients, even those with left ventricular hypertrophy. This may reflect the consequences on the left ventricle of long-term antihypertensive treatment. If complex ventricular arrhythmias are implicated in the excess of sudden deaths in hypertensive patients, this might be an important factor.

Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.

OBJECTIVE: To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol < or = 6.5 mmol/l. DESIGN: Prospective, randomized, open, blinded endpoint trial with a double-blinded 2 x 2 factorial component. SETTING: Patients were recruited mainly from general practices. PATIENTS: Men and women aged 40-79 were eligible if their blood pressure was > or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization. INTERVENTIONS: Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily. MAIN OUTCOME MEASURE: Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). RESULTS: 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors. CONCLUSIONS: The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.

Calcium antagonists and the diabetic patient: a response to recent controversies.

The results of 2 recently published studies have been interpreted as suggesting that calcium antagonists are unsafe for the management of hypertension in patients with diabetes. These 2 studies, the Fosinopril versus Amlodipine Cardiovascular Events Randomized Trial (FACET) and Appropriate Blood Pressure Control in Diabetes (ABCD), showed that angiotensin-converting enzyme (ACE) inhibitors may be preferable to calcium antagonists for managing hypertension in diabetic patients; they do not, however, show any harm attributable to calcium antagonists. Indeed, results of the FACET study suggest that the combination of an ACE inhibitor and a calcium antagonist is effective antihypertensive therapy. This suggestion is supported by findings in the Systolic Hypertension in Europe (Syst-Eur) Study, which revealed outstanding benefits of either a calcium antagonist alone or a calcium antagonist combined with an ACE inhibitor among diabetic patients with hypertension. The premature termination of the hypertensive arm of the ABCD study was puzzling because, although 2 of 13 subgroups of 1 of the 5 possible secondary endpoints in this part of the trial were apparently favorably affected by the use of the ACE inhibitor rather than the calcium antagonist, such a finding was compatible with chance alone. If the results of the FACET and ABCD studies are considered in the context of the best available data arising from large randomized controlled trials, one may conclude that calcium antagonists are not harmful or contraindicated in hypertensive patients with diabetes and that the combination of an ACE inhibitor and a calcium antagonist is effective for the management of hypertension in diabetic patients.

Higher blood pressures of urban migrants from an African low-blood pressure population are not due to selective migration.

A longitudinal study has shown that migrants from a remote Kenyan low-blood pressure (BP) community living in an urban environment had significantly higher BPs than a cohort of matched, nonmigrant controls. Selective migration was thought to be the likely explanation for this observation, but the BPs of 90 males studied prior to migration were almost identical to those found in the age-matched rural based controls studied in the low-BP community from which they came (120.9/59.0 mm Hg vs 120.5/60.1 mm Hg). Hence, in view of these premigration data supported by other evidence from the Kenyan Luo Migrant Study, it appears that the higher BP levels of the Luo migrants are not due to selective migration but are consequent upon environmental changes, including changes in electrolyte intake, which occur rapidly after migration.

QT intervals and QT dispersion as measures of left ventricular hypertrophy in an unselected hypertensive population.

Electrocardiographic (ECG) QT intervals and dispersion correlate with echocardiographic left ventricular mass index (LVMI) in groups of selected essential hypertensives. We tested the strength of this relationship in a large group of unselected hypertensives to assess whether QT measurements may be a simple screening test for LVH in clinical practice. In a cross-sectional study of 386 unselected hypertensive subjects, maximal QT intervals (QTmax), QT dispersion (QTdisp), and ECG voltages (Sokolow-Lyon and Cornell sex-specific voltages) were measured from 12-lead ECG. The LVMI correlated most strongly with Cornell voltage (linear regression r = 0.44, P < .001). The strongest relationship between LVMI and QT parameters was with QTmax, (r = 0.25, P < .001). This relationship weakened using heart rate-corrected QTmax. Correlations between LVMI and QTdisp were weak, whether or not they were corrected for heart rate. Sokolow-Lyon voltages, Cornell voltage and QTmax, but not QTdisp, were independently predictive of LVMI after adjustment for age, sex, race, and the other ECG parameters. Receiver operating characteristic (ROC) curve analyses demonstrated that no QT parameter performed better than simple ECG voltage criteria in the detection of LVH. In conclusion, QTmax, the QT parameter most strongly associated with LVMI, was independently associated with LVMI after adjustment for standard ECG voltage criteria. However, as an isolated measure it was no better than simple ECG voltage criteria as a screening test for LVH in clinical practice.

The effects on cardiac arrhythmias of antihypertensive therapy causing regression of left ventricular hypertrophy.

To examine the effects of antihypertensive therapy causing regression of left ventricular hypertrophy on cardiac arrhythmias, 26 hypertensive subjects were treated with ramipril with felodipine if required, and followed for 6 months after blood pressure control. Compared with baseline, left ventricular mass index (LVMI) was significantly reduced both at blood pressure control and after a further 6 months of treatment (baseline, blood pressure control, 6 months after blood pressure control; LVMI 142 +/- 3.6, 131 +/- 3.4, 123 +/- 3.8* g/m2, *P < .01 compared with baseline). There was a significant relationship between the decrease in systolic blood pressure and the decrease in LVMI after 6 months of blood pressure control compared with baseline (r = 0.41, P = .05). Compared with baseline, the average total number of ventricular ectopics decreased after blood pressure was controlled (88 +/- 59 and 21 +/- 12 respectively); however this reduction was not maintained after 6 months of further treatment, either before (78 +/- 50) or after drug washout (86 +/- 40). Compared with baseline (639 +/- 590) supraventricular ectopic total was not initially reduced after blood pressure control (650 +/- 604), but was reduced after a further 6 months of treatment (294 +/- 261). This reduction was maintained after drug washout (267 +/- 254), although this did not reach statistical significance. Radionuclide scanning at baseline was not a predictor of patients with the highest risk of arrhythmia and there was no correlation between improvement or worsening of a defect with changes in ventricular ectopic total. In conclusion, antihypertensive therapy with ramipril and felodipine, although causing regression of left ventricular hypertrophy did not lead to a sustained reduction in ventricular ectopic total.

Ethnic differences in the identification of left ventricular hypertrophy in the hypertensive patient.

Left ventricular hypertrophy (LVH) is more prevalent in black than white hypertensives, but this difference is greater when identified by electrocardiography (ECG) than by echocardiography. We evaluated the proposal that current ECG criteria for LVH are less specific, and therefore, less useful, in blacks than whites. In a retrospective cross-sectional study, 408 subjects (271 white, 137 black) referred to a hypertension clinic for assessment of hypertension underwent measurement of blood pressure, ECG voltages (Sokolow-Lyon and Cornell sex-specific), and echocardiographic left ventricular mass index (LVMI). Black subjects had greater ECG voltages than whites, even when closely matched for LVMI. In black subjects, current ECG criteria were twice as sensitive as in whites (Sokolow-Lyon: 44.9% v 22.5%, P = .003. Cornell: 30.4% v 15.7%, P = .03). They were less specific in blacks using the Sokolow-Lyon criteria (73.5% v 86.8%, P = .02) but this failed to reach significance using the Cornell criteria (83.8% v 91.8%, P = .07). When voltage criteria were adjusted to give matched sensitivities and specificities, respectively, differences in specificity and sensitivity were no longer apparent. Receiver operating characteristic curve analyses confirmed no significant differences in overall performance of either ECG criteria between blacks and whites. In conclusion, ECG detection of LVH is insensitive in both ethnic groups. Sensitivity is higher in blacks due to higher LVMI in those with LVH. Apparent differences in specificity are due to ethnic differences in ECG voltages that are unrelated to differences in LVMI. When these differences are taken into account, there are no overall differences in test accuracy. However, given the prognostic importance of the detection of LVH, currently accepted ECG voltage criteria for the detection of LVH remain of equal or greater value in black hypertensives compared with whites.

Combined oral contraceptives, smoking, and cardiovascular risk.

STUDY OBJECTIVE: To assess age specific incidence and mortality of stroke, acute myocardial infarction (AMI), and idiopathic venous thromboembolism (VTE) associated with use of modern low dose combined oral contraceptives (OCs) and the interaction with smoking. DESIGN: Hospital-based case-control study. SETTING: Hospitals in Oxford region in the United Kingdom, which covered a defined population, during the period 1989-1993. METHODS: Relative risk estimates from the WHO Collaborative Study and observed incidence rates from the Oxford region were used to estimate age specific incidence of each disease among women without cardiovascular risk factors and model total cardiovascular incidence and mortality. RESULTS: Among women who did not use OCs, smoke nor had any other cardiovascular risk factors, total incidence of stroke and AMI were less than 2 events per 100,000 woman years in those aged 20-24 years and rose exponentially with age to 8 events per 100,000 among women aged 40-44 years. Incidence of idiopathic VTE among women who did not use OCs rose linearly with age (from 3.3 per 100,000 at ages 20-24 years to 5.8 per 100,000 at ages 40-44 years). The increased risk of idiopathic VTE associated with OC use among non-smokers constituted over 90% of all cardiovascular events for women aged 20-24 years and more than 60% in those aged 40-44 years. Fatal cardiovascular events were dominated by haemorrhagic stroke and AMI, and among OC users who smoked these two diseases accounted for 80% of cardiovascular deaths among women aged 20-24 years, rising to 97% among those aged 40-44 years. Cardiovascular mortality associated with smoking was greater than that associated with OC use at all ages. Attributable risk associated with OC use was 1 death per 370,000 users annually among women aged 20-24 years, 1 per 170,000 at ages 30-34 years, and 1 per 37,000 at ages 40-44 years. Among smokers, the cardiovascular mortality attributable to OC use was estimated to be about 1 per 100,000 users annually among women aged less than 35 years, and about 1 per 10,000 users annually among those above the age of 35 years. CONCLUSION: The incidence of fatal cardiovascular events among women aged less than 35 years is low. The VTE risk associated with OC use is the largest contributor to OC induced adverse effects. The potentially avoidable excess VTE risk associated with the newer progestogens desogestrel and gestodene would account for a substantial proportion of total cardiovascular morbidity in this age group. For women over age 35 years the absolute risks associated with OC use and smoking are greater because of the steeply rising incidence of arterial diseases. The combination of smoking and OC use among such women is associated with particularly increased risks. Any potential reduction in AMI or stroke risk with use of third generation OCs would be a more important consideration among older compared with younger women, particularly if they smoke. However, the mortality associated with smoking is far greater than that associated with OC use (of any type) at all ages.