Effects of CPAP on systemic hypertension in OSAH: a monocentric, observational, cohort study.

BACKGROUND: Obstructive sleep apnea-hypopnea (OSAH) is a risk factor for development of systemic arterial hypertension (SAH) and can worse the control of established SAH. We investigated the effects of long-term continuous positive airway pressure (CPAP) treatment in controlling and preventing SAH in a large cohort of subjects referred for sleep study for suspected OSAH. METHODS: In 495 subjects of whom 422 with OSAH and 73 without OSAH, the clinical history was obtained, arterial blood pressure was measured and the current anti-hypertensive drugs was recorded at diagnosis and/or at CPAP start. Subjects were interviewed after a follow-up period of (mean ± SD) 3.4 ± 2.2 yr (range 1-8 yr) and divided in patients with moderate-to-severe OSAH (n = 125) who referred to use CPAP regularly for at least 4 h every night (group 1), with moderate-to-severe OSAH (n = 70) who refused or abandoned the CPAP treatment after few weeks (group 2), with mild OSAH (n = 227) with no CPAP indication (group 3) and simple snorers or normals (n = 73) (group 4). For each group clinical status, BMI, and changes in SAH therapy and occurrence of SAH were assessed at the follow-up. RESULTS: At the follow-up, a higher risk of increasing treatment for SAH was found for group 2 and group 3 versus group 1 (OR = 5, 95%CI 1-20, p < 0.01 and OR = 3, 95%CI 1-10, p < 0.05), respectively. The occurrence of SAH was lower (p < 0.001) in the group 1 (1.9%), vs group 2 (35.9%), 3 (21.1%) and 4 (18.6%). CONCLUSIONS: In moderate-to-severe OSAH patients, long-term CPAP treatment significantly reduces the development of SAH and, in those with SAH at baseline, the need of anti-hypertensive drugs.

Chronic nitrate therapy is associated with different presentation and evolution of acute coronary syndromes: insights from 52,693 patients in the Global Registry of Acute Coronary Events.

AIMS: Brief episode(s) of ischaemia may increase cardiac tolerance to a subsequent major ischaemic insult ('preconditioning'). Nitrates can pharmacologically mimic ischaemic preconditioning in animals. In this study, we investigated whether antecedent nitrate therapy affords protection toward acute ischaemic events using data from the Global Registry of Acute Coronary Events. METHODS AND RESULTS: The dataset comprised 52,693 patients from 123 centres in 14 countries: 42,138 (80%) were nitrate-naïve and 10,555 (20%) were on chronic nitrates at admission. In nitrate-naïve patients, admission diagnosis was ST-segment elevation myocardial infarction (STEMI) in 41%, whereas 59% presented with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). In contrast, only 18% nitrate users showed STEMI, whereas 82% presented with NSTE-ACS. Thus, among nitrate users clinical presentation was tilted toward NSTE-ACS by more than four-fold, STEMI occurring in less than one of five patients (P < 0.0001). After adjustment (age, sex, medical history, prior therapy, revascularization, previous angina), chronic nitrate use remained independent predictor of NSTE-ACS (OR 1.36; 95% CI 1.26-1.46; P < 0.0001). Furthermore, regardless of presentation, within both STEMI and NSTEMI populations, antecedent nitrate use was associated with significantly lower levels of CK-MB and troponin (P < 0.0001 for all). CONCLUSION: In this large multinational registry, chronic nitrate use was associated with a shift away from STEMI in favour of NSTE-ACS and with less release of markers of cardiac necrosis. These findings suggest that in nitrate users acute coronary events may develop to a smaller extent. Randomized, placebo-controlled trials are warranted to establish whether nitrate therapy may pharmacologically precondition the heart toward ischaemic episodes.

[Obstructive sleep apnea syndrome and cardiovascular diseases]. / Sindrome dell'apnea ostruttiva notturna e malattie cardiovascolari.

Obstructive sleep apnea (OSA) syndrome is one of the most common respiratory disorders in humans. There is emerging evidence linking OSA to vascular disease, particularly hypertension. The underlying pathophysiological mechanisms that link OSA to cardiovascular diseases such as hypertension, congestive heart failure and atrial fibrillation are not entirely understood, although they certainly include mechanical events, increased sympathetic activity and oxidative stress. This review will examine the evidence and mechanisms linking OSA syndrome to cardiovascular disease.

Day-to-day variability of electrocardiographic diagnosis of left ventricular hypertrophy in hypertensive patients. Influence of electrode placement.

OBJECTIVE: Although electrocardiography (ECG) is recommended in all subjects with hypertension, no information is available on the influence exerted by random changes in the placement of electrodes on the day-to-day variability of ECG criteria for diagnosis of left ventricular hypertrophy (LVH). METHODS: In a multicentre, randomized study, two standard 12-lead ECG were recorded, 24 h apart, from 276 consecutive hypertensive patients (mean age 65 +/- 12 years, 49.6% men). Overall, 142 patients were randomized to ECG with the position of electrodes marked on the skin using a dermographic pen and 134 to traditional ECG without marking the position of electrodes. Day-to-day variability of ECG criteria for LVH was compared between the two groups. RESULTS: Coefficients of variation (SD of the difference between paired voltage measurements divided by the mean value) varied consistently among subjects randomized to ECG without dermographic pen, ranging from 30% (R wave in lead I) to 81% (R wave in lead V5). Dermographic pen led to a lesser variability of ECG voltages with consequent reduction in the coefficients of variation, which ranged from 26% (R-wave amplitude in lead I) to 43% (R-wave amplitude in lead V5). The proportion of subjects who changed classification status for LVH ('reclassification rate') from the first to the second ECG session (LVH present in session 1 and absent in session 2, or vice versa) decreased for effect of dermographic pen from 11 to 4% (P = 0.040) with the Cornell voltage, from 19 to 11% (P = 0.029) with the Sokolow-Lyon voltage, and from 18 to 7% with the Romhilt-Estes criterion (P = 0.018), but not with other criteria. In particular, the typical strain and the Cornell strain were associated with the lowest reclassification rates regardless of dermographic pen. CONCLUSIONS: Random changes in the position of ECG electrodes strongly impair the day-to-day reproducibility of Cornell voltage, Sokolow-Lyon and Romhilt-Estes criteria for LVH. The typical strain and Cornell strain criteria showed a lesser spontaneous day-to-day variability.

Angiotensin-converting enzyme inhibitors and calcium channel blockers for coronary heart disease and stroke prevention.

We investigated whether protection from coronary heart disease (CHD) and stroke conferred by angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs) in hypertensive or high-risk patients may be explained by the specific drug regimen. We extracted summary statistics regarding CHD and stroke from 28 outcome trials that compared either ACEIs or CCBs with diuretics, beta-blockers, or placebo for a total of 179,122 patients, 9509 incident cases of CHD, and 5971 cases of stroke. CHD included myocardial infarction and coronary death. In placebo-controlled trials, ACEIs decreased the risk of CHD (P<0.001), and CCBs reduced stroke incidence (P<0.001). There were no significant differences in CHD risk between regimens based on diuretics/beta-blockers and regimens based on ACEIs (P=0.46) or CCBs (P=0.52). The risk of stroke was reduced by CCBs (P=0.041) but not by ACEIs (P=0.15) compared with diuretics/beta-blockers. Because heterogeneity between trials was significant, we investigated potential sources of heterogeneity by metaregression. Examined covariates were the reduction in systolic blood pressure (BP), drug treatment (ACEIs versus CCBs), their interaction term, sex, age at randomization, year of publication, and duration of treatment. Prevention of CHD was explained by systolic BP reduction (P<0.001) and use of ACEIs (P=0.028), whereas prevention of stroke was explained by systolic BP reduction (P=0.001) and use of CCBs (P=0.042). These findings confirm that BP lowering is fundamental for prevention of CHD and stroke. However, over and beyond BP reduction, ACEIs appear superior to CCBs for prevention of CHD, whereas CCBs appear superior to ACEIs for prevention of stroke.

Calcium channel blockade to prevent stroke in hypertension: a meta-analysis of 13 studies with 103,793 subjects.

BACKGROUND: The possibility that specific antihypertensive treatments may prevent the occurrence of stroke more effectively than other treatments remains unproved. We undertook a meta-analysis to assess whether calcium channel blockers (CCBs) are associated with a lesser risk of stroke as compared with other antihypertensive drugs. METHODS: Through Medline we identified 13 major studies conducted in hypertensive subjects for a total of 103,793 subjects. Overall, there were 4040 incident cases of stroke, 1789 among 43,053 subjects randomized to CCBs and 2251 among 60,740 subjects randomized to different antihypertensive drugs. RESULTS: Considering all 13 trials, a pooled reduction in the risk of stroke was observed among subjects allocated to CCBs (odds ratio 0.90, 95% confidence interval [95% CI] 0.84-0.96; P =.002). The risk of stroke was significantly lower among subjects allocated to dihydropyridine CCBs than among those randomized to alternative drugs (odds ratio 0.90, 95% CI 0.84-0.97; P =.006), whereas the effect of non-dihydropyridine CCBs did not achieve significance (odds ratio 0.92, 95% CI 0.81-1.04). In a meta-regression analysis of these trials, the protection from stroke conferred by CCBs appeared unrelated to the degree of systolic blood pressure reduction. CONCLUSIONS: These findings suggest that CCBs decrease the risk of stroke more effectively than other treatments in patients with essential hypertension and that such an effect might not be completely explained by a better antihypertensive response. Calcium channel blockers should be considered in hypertensive subjects at increased risk of stroke.

Meta-Analysis of effectiveness or lack thereof of angiotensin-converting enzyme inhibitors for prevention of heart failure in patients with systemic hypertension.

We undertook a meta-analysis of large, randomized controlled trials in hypertensive subjects that compared angiotensin-converting enzyme (ACE) inhibitors with different classes of antihypertensive drugs. Compared with subjects randomized to drugs different from ACE inhibitors, those treated with ACE inhibitors did not show a different risk of congestive heart failure (CHF) (odds ratio 1.03, 95% confidence interval 0.96 to 1.12, p = 0.407). The degree of protection from CHF associated with the use of ACE inhibitors showed a nonsignificant trend to increase with age and the degree of blood pressure control. Thus, the hypothesis that ACE inhibitors are superior to other antihypertensive drugs for prevention of CHF in hypertension remains unproven.

Improved cardiovascular risk stratification by a simple ECG index in hypertension.

BACKGROUND: We determined the prognostic value of the Cornell/strain [C/S] index, a simple electrocardiographic (ECG) index for left ventricular hypertrophy (LVH) defined by the presence of either a classic strain pattern or a Cornell voltage (sum of R in aVL + S in V(3)) >2.0 mV in women or 2.4 mV in men, or both. METHODS: In a prospective, cohort study, 2190 initially untreated subjects (age 51 [+/- 12], 47% women) with essential hypertension without prior events were followed for up to 14 years (median, 5 years). RESULTS: Prevalence of LVH at entry was 16.3% by using the C/S index, which yielded 33.6% sensitivity and 91.0% specificity. Other ECG criteria for LVH including Sokolow-Lyon, Romhilt-Estes, Framingham, Cornell, and strain alone, achieved a lower sensitivity and prevalence. Over the subsequent follow-up, 244 patients experienced a first major cardiovascular event. Event rate (x 100 person-years) was 2.01 in those without and 4.44 in those with LVH by the C/S index (P <.001). After adjustment for age, sex, smoking, and other counfounders, the C/S index identified subjects at increased risk of events (relative risk 1.76; 95% confidence interval 1.32-2.33). The C/S index achieved the highest population-attributable risk (16.1%) for cardiovascular events. CONCLUSIONS: A simple ECG index that can be quickly measured from nondigital machines and without algorithms identifies LVH in a consistent proportion (16.3%) of hypertensive subjects. The LVH defined by such technique allows identification of individuals at high risk for cardiovascular events.

Association between periodontal disease and left ventricle mass in essential hypertension.

Chronic periodontitis has been associated with an increased risk for cardiovascular disease. Left ventricular mass is an established independent predictor of cardiovascular disease. In the present cross-sectional study, we tested the association between periodontitis and left ventricular mass in subjects with essential hypertension. One hundred four untreated subjects with essential hypertension underwent clinical examinations, including echocardiographic study, laboratory tests, and assessment of periodontal status according to the community periodontal index of treatment needs (CPITN). With increasing severity of periodontitis, there was a progressive increase in left ventricle mass. Mean values (g/height2.7) were 39.0 (+/-2.7) in CPITN 0 (periodontal health), 40.2 (+/-6.4) in CPITN 1 (gingival bleeding), 42.7 (+/-6.8) in CPITN 2 (calculus), 51.4 (+/-11.7) in CPITN 3 (pockets 4 to 5 mm), and 76.7 (+/-11.3) in CPITN 4 (pockets > or =6 mm) (overall F 51.2; P<0.0001). Body surface area (P=0.04), systolic (P<0.0001) and diastolic (P<0.01) blood pressure, and left ventricular mass (P<0.0001) were determinants of a composite of CPITN 3 and 4. In a multivariate logistic analysis, left ventricular mass was the sole determinant (P<0.0001) of CPITN stages 3 and 4. Our findings suggest a direct association between severity of periodontitis and left ventricular mass in subjects with essential hypertension. Periodontal evaluation might contribute to refine cardiovascular risk assessment in hypertensive subjects.

Effects of acute myocardial ischemia on QT dispersion by dipyridamole stress echocardiography.

Increased dispersion of the QT interval has been observed during pacing or exercise stress testing in patients with coronary artery disease (CAD). It has not been established whether this phenomenon is a consequence of ischemia. Therefore, we sought to evaluate whether dipyridamole-induced myocardial ischemia, as directly detected by echocardiographic monitoring of regional contractile function, would affect QT dispersion. Twenty-four patients with nonsignificant and 34 patients with significant CAD but no previous myocardial infarction underwent dipyridamole stress echocardiography while not taking medications. QT dispersion was measured on a 12-lead electrocardiogram at baseline and at various times after dipyridamole infusion. Dipyridamole infusion did not influence QT dispersion in patients without CAD. QT dispersion was similarly unaffected in patients with CAD in whom dipyridamole did not induce wall motion abnormalities. In contrast, in patients with positive dipyridamole stress test findings, QT dispersion increased from 60 +/- 17 ms at baseline to 94 +/- 25 ms during peak infusion (p <0.0001), with a time course mirroring that of development of contractile abnormalities. QT dispersion returned to 63 +/- 25 ms upon relief of ischemia by administration of aminophylline. The increase in QT dispersion was significantly related to the extent of contractile dysfunction induced by dipyridamole. Although ST-segment depression occurred in only 40% of patients with positive dipyridamole stress test findings, 88% of such patients had an increase in QT dispersion. Analysis of the receiver-operating characteristic curve showed that a QT dispersion increase of > or =20 ms identified positive findings for dipyridamole stress echocardiography with 68% sensitivity and 91% specificity. Thus, QT dispersion is acutely affected by myocardial ischemia induced by the administration of dipyridamole. Measurement of QT dispersion may improve detection of stress-induced ischemia on surface electrocardiograms.

Atrial fibrillation in hypertension: predictors and outcome.

Incidence, determinants, and outcome of atrial fibrillation in hypertensive subjects are incompletely known. We followed for up to 16 years 2482 initially untreated subjects with essential hypertension. At entry, all subjects were in sinus rhythm. Subjects with valvular heart disease, coronary artery disease, preexcitation syndrome, thyroid disorders, or lung disease were excluded. During follow-up, a first episode of atrial fibrillation occurred in 61 subjects at a rate of 0.46 per 100 person-years. At entry, subjects with future atrial fibrillation differed (all P<0.05) from those without by age (59 versus 51 years), office, and 24-hour systolic blood pressure (165 and 144 versus 157 and 137 mm Hg, respectively), left ventricular mass (58 versus 49 g/height[m](2.7)), and left atrial diameter (3.89 versus 3.56 cm). Age and left ventricular mass (both P<0.001) were the sole independent predictors of atrial fibrillation. For every 1 standard deviation increase in left ventricular mass, the risk of atrial fibrillation was increased 1.20 times (95% CI, 1.07 to 1.34). Atrial fibrillation became chronic in 33% of subjects. Age, left ventricular mass, and left atrial diameter (all P<0.01) were independent predictors of chronic atrial fibrillation. Ischemic stroke occurred at a rate of 2.7% and 4.6% per year, respectively, among subjects with paroxysmal and chronic atrial fibrillation. These data indicate that in hypertensive subjects with sinus rhythm and no other major predisposing conditions, risk of atrial fibrillation increases with age and left ventricular mass. Increased left atrial size predisposes to chronicization of atrial fibrillation.

Risk of cardiovascular disease in relation to achieved office and ambulatory blood pressure control in treated hypertensive subjects.

OBJECTIVE: We investigated the prognostic impact of 24-h blood pressure control in treated hypertensive subjects. BACKGROUND: There is growing evidence that ambulatory blood pressure improves risk stratification in untreated subjects with essential hypertension. Surprisingly, little is known on the prognostic value of this procedure in treated subjects. METHODS: Diagnostic procedures including 24-h noninvasive ambulatory blood pressure monitoring were undertaken in 790 subjects with essential hypertension (mean age 48 years) before therapy and after an average follow-up of 3.7 years (2,891 patient-years). RESULTS: At the follow-up visit, 26.6% of subjects achieved adequate office blood pressure control (<140/90 mm Hg), and 37.3% of subjects achieved adequate ambulatory blood pressure control (daytime blood pressure <135/85 mm Hg). Months or years after the follow-up visit, 58 patients suffered a first cardiovascular event. Event rate was lower (0.71 events/100 person-years) among the subjects with adequate ambulatory blood pressure control than among those with higher blood pressure levels (1.87 events/100 person-years) (p = 0.0026). Ambulatory blood pressure control predicted a lesser risk for subsequent cardiovascular disease independently of other individual risk factors (RR 0.36; 95% confidence intervals: 0.18 to 0.70; p = 0.003), including age, diabetes and left ventricular hypertrophy. Office blood pressure control was associated with a nonsignificant lesser risk of subsequent events (RR 0.63; 95% confidence intervals: 0.31 to 1.31; p = NS). In-treatment ambulatory blood pressure was more potent than pre-treatment blood pressure for prediction of subsequent cardiovascular disease. CONCLUSIONS: Ambulatory blood pressure control is superior to office blood pressure control for prediction of individual cardiovascular risk in treated hypertensive subjects.