Novel Electrocardiographic Patterns for the Prediction of Hypertensive Disorders of Pregnancy--From Pathophysiology to Practical Implications.

Hypertensive disorders of pregnancy are a major cause of poor outcome, including placental abruption, organ failure, cerebrovascular accident and disseminated intravascular coagulation. These disorders are associated with increased fetal risk of intrauterine growth restriction, intrauterine death and prematurity. Electrocardiography (ECG) recently emerged as a useful tool to evaluate cardiovascular complications during pregnancy. Specifically, left atrial abnormalities detected by standard ECG are associated with a fourfold increased risk of developing hypertensive disorders during pregnancy. The mechanisms linking left atrial abnormality on ECG with hypertensive disorders are still elusive. Several mechanisms, possibly reflected by abnormal left atrial activation on ECG, has been suggested. These include increased reactivity to angiotensin II and up-regulation of angiotensin type 1 receptors, with activation of autoantibodies targeting these receptors.

Efficacy and safety profile of aliskiren: practical implications for clinicians.

Renin-angiotensin-system (RAS) is an enzymatic cascade that plays a pivotal role in the development of arterial hypertension, kidney disease and cardiovascular disease. Inhibition of the RAS with angiotensin converting enzyme (ACE) inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) has proved to be a successful strategy for the treatment of hypertension and related cardiovascular disorders. However, by reducing feedback inhibition of renin release, the effects of ACE-Is and ARBs lead to an increase in plasma renin concentration (PRC) and activity (PRA), limiting a complete inhibition of the RAS. Consequently the effects of a different pharmacological strategy that completely blocks the RAS upstream has been assessed in the last years. In this context, aliskiren is the first representative of a new class of non-peptide orally active renin inhibitor that blocks the RAS at its rate-limiting step and induces a net reduction in PRA, angiotensin II and aldosterone levels. Aliskiren effectively reduces blood pressure as a monotherapy as well in combination therapy. In addition, aliskiren has a placebo-like tolerability profile at the licensed doses of 150 mg and 300 mg. Aliskiren also exhibits additive effects on blood pressure reduction when combined with drugs that lead to a reactive increase in the PRA, such as diuretics, ACE-Is or ARBs. In previous studies, aliskiren showed beneficial effects in patients with arterial hypertension and associated clinical conditions. However, later trials indicated that the use of aliskiren should be avoided in patients with renal failure or receiving ACE-Is or ARBs. The main aim of this review is to summarize the available data on its efficacy and safety profile, highlighting clinical implications from recent trials.

Neutrophil count and ambulatory pulse pressure as predictors of cardiovascular adverse events in postmenopausal women with hypertension.

BACKGROUND: Elevated neutrophil count, a marker of systemic inflammation, has been suggested as a prognostic marker of cardiovascular disease in postmenopausal women with hypertension. We tested the hypothesis that an association exists between elevated neutrophil count and increased arterial stiffness, as reflected by a wide pulse pressure (PP), in this population of women. We also tested PP as predictor of cardiovascular adverse events in this population. METHODS: We analyzed data relating to 886 postmenopausal women with hypertension, consecutively enrolled in a prospective registry. Ambulatory blood pressure monitoring was carried out at entry in all the subjects. The median duration of follow-up was 7.4 years (range: 1-21 years). RESULTS: There was a direct relationship between neutrophil count and 24-h ambulatory PP (P < 0.0001) and this association remained significant after adjusting for age, serum glucose, and left ventricular (LV) hypertrophy at electrocardiogram (ECG) (all P < 0.01). During follow-up there were 121 first-time major cardiovascular (CV) events. The rate (× 100 patient-years) of CV events was 1.02, 1.36, and 3.75, respectively in the three tertiles of the distribution of 24-h PP (P < 0.0001). In a multivariate analysis, 24-h ambulatory PP and neutrophil count were independent predictors of total CV events after adjusting for the influence of other risk markers. In particular, for each 10 mm Hg increase in 24-h PP, there was a 73% higher risk for total CV events (P = 0.015). Office-recorded PP did not achieve significance when forced in the same model. CONCLUSIONS: Increased arterial stiffness, as reflected in high values of 24-h ambulatory PP, is an adverse prognostic marker in postmenopausal women with hypertension, possibly as an additional correlate of systemic inflammation.

Additive value of standard ECG for the risk prediction of hypertensive disorders during pregnancy.

Prediction of hypertensive complications during pregnancy remains limited, especially in healthy and initially normotensive women. We conducted a prospective screening study for hypertensive complications in pregnant women. We studied 221 nulliparous healthy and normotensive women with singleton pregnancies whose first routine visit was carried out before the twelfth week of gestation. We tested several demographic, clinical and laboratory variables as predictors of a composite pool of prespecified events, including gestational hypertension, preeclampsia or eclampsia. We analyzed the potential additive role of ECG in the identification of women at increased risk of hypertensive disorders. Mean age at entry was 30 years. During pregnancy, there were 28 prespecified events (22 women with gestational hypertension, 5 with preeclampsia and 1 with eclampsia). In univariate analyses, blood pressure (BP), weight, body mass index (BMI) and left atrial (LA) abnormality detected by ECG in lead V(1) showed an association with the risk of hypertensive disorders (all P<0.05). In a multivariable analysis, only mean BP (OR: 3.08, 95% confidence interval (CI): 1.61-5.92; P=0.001 for each 10 mm Hg increase) and LA abnormality in lead V(1) (OR: 4.35, 95% CI: 1.84-10.31; P=0.001) were independent predictors of hypertensive disorders. The final model discriminated well between women who developed hypertensive disorders and women who remained normotensive (AUC=0.75; 95% CI: 0.67-0.84; P<0.0001). This study suggests that standard ECG is valuable to refine risk stratification for hypertensive disorders in initially normotensive pregnant women. LA abnormality, easily detected by simple visual inspection of the traditional ECG, and mean arterial pressure (MAP), allows a rapid and effective risk stratification for hypertensive disorders.

Electrocardiographic abnormalities of left ventricular repolarization: prognostic implications in hypertensive post-menopausal women.

BACKGROUND: Although repolarization abnormalities on ECG are frequent in post-menopausal hypertensive women, their prognostic value in these women is uncertain. METHODS: We analyzed 908 hypertensive post-menopausal women consecutively included in the PIUMA (Progetto Ipertensione Umbria Monitoraggio Ambulatoriale) study. The median duration of follow-up was 8.6 years (range: 1-21). All women were untreated at entry. Drug treatment during follow-up was adjusted to single individuals. Standard 12-lead ECG was carried out at entry. The Minnesota Coding was used to define minor and major ("typical strain") repolarization abnormalities. DESIGN: prospective observational study in essential hypertension. RESULTS: Mean age at entry was 60 years. At baseline, ECG was normal in 707 women, minor ST-T changes were noted in 152 women, and a typical strain pattern was present in 49 subjects. Predictors of typical strain were age, diabetes and systolic blood pressure (BP). During follow-up there were 119 new cardiovascular (CV) events and 75 all-cause deaths. Typical strain was associated with a threefold higher risk of CV disease (HR: 3.16; 95% CI: 1.59-6.31; p=0.001) after adjustment for the significant influence of age, diabetes, serum creatinine, systolic BP and HDL-cholesterol. Women with minor LV repolarization abnormalities showed a non-significant excess risk of CV disease when compared with women with normal LV repolarization (HR: 1.25; 95% CI: 0.69-2.26; p=0.467). Similar results were obtained for all-cause mortality. CONCLUSIONS: Typical strain pattern, an easily detectable marker of altered LV repolarization, identifies post-menopausal hypertensive women at increased risk of CV disease and all-cause mortality.

Neutrophil count for the identification of postmenopausal hypertensive women at increased cardiovascular risk.

OBJECTIVE: High white blood cell and neutrophil counts identify patients at increased cardiovascular risk in various clinical settings. However, the prognostic value of white blood cell and neutrophil counts in hypertensive postmenopausal women is unknown. We tested the independent prognostic value of total white blood cell and neutrophil counts for cardiovascular events in hypertensive postmenopausal women. METHODS: We examined 298 initially untreated postmenopausal women with essential hypertension who were part of Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA). Mean duration of follow-up was 8 years (range 1-20 years). Treatment was tailored to each individual. RESULTS: Mean age at entry was 59 years. Diabetic women comprised 9.1% of the group, and current smokers comprised 17.5% of the group. During follow-up, 31 new major cardiovascular events occurred. In univariable analyses, age, diabetes, serum creatinine, blood pressure, left ventricular hypertrophy, and neutrophil count showed an association with the risk of events (all P<.05). In a multivariable Cox analysis, after adjustment for traditional cardiovascular risk factors, for each 1.25x10 (1 standard deviation) increase in neutrophil count there was a 67% higher risk of cardiovascular events (hazard ratio 1.67, 95% confidence interval 1.32-2.07; P<.001). Furthermore, neutrophil count showed robust incremental predictive value for cardiovascular events, in addition to traditional risk factors. Total white blood cell count did not show any association with cardiovascular events. CONCLUSION: A high peripheral neutrophil count identifies postmenopausal hypertensive women at increased risk of cardiovascular disease. Such relation appears to be independent of traditional risk factors. LEVEL OF EVIDENCE: III.

Validation of the A&D wrist-cuff UB-511 (UB-512) device for self-measurement of blood pressure.

OBJECTIVES: To determine the accuracy of the A&D UB-511 (UB-512) oscillometric wrist-cuff device for self-measurement of blood pressure, the only difference between the two devices being the size of storage memory. METHODS: Device evaluation was performed according to the modified British Hypertension Society protocol released in 1993. Eighty-five study participants with characteristics outlined in the British Hypertension Society protocol were recruited among those attending our out-patient clinic. The device was evaluated according to the various steps of the protocol. The non-dominant arm was used for blood pressure measurement. To maintain the wrist at cardiac level during validation, the arm was kept horizontal at the mid-sternum level and supported by a soft table. The wrist was kept extended. Sequential readings were taken for the main validation test. Outcome was classified according to the criteria of the British Hypertension Society recommendations, which are based on four strata of accuracy differing from the mercury standard by 5, 10 and 15 mmHg, or more. RESULTS: The device achieved a British Hypertension Society grade B for systolic and a grade B for diastolic blood pressure. The device tended to overestimate arm blood pressure, the mean difference (+/-1 SD) between device and observers being 4.3+/-8.7 mmHg for systolic blood pressure and 3.7+/-8.1 mmHg for diastolic blood pressure for observer 2, and 4.4+/-8.6 mmHg for systolic blood pressure and 3.8+/-7.9 mmHg for diastolic blood pressure for observer 1. In a logistic regression analysis, age was the sole predictor of an achieved difference between device and mercury column by 5 mmHg or less (hazard ratio 1.020; 95% confidence interval 1.003-1.04; P=0.024). CONCLUSIONS: These data show that the A&D UB-511 (UB-512) device satisfies the British Hypertension Society recommendations with a grade B/B. The device tends to overestimate cuff blood pressure and its accuracy increases with age.

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.

Validation of the A&D UA-705 device for self-measurement of blood pressure according to the British Hypertension Society protocol.

OBJECTIVES: We tested the accuracy of the UA-705 blood pressure semi-automatic monitor. METHODS: Device evaluation was performed according to the modified British Hypertension Society protocol released in 1993. Eighty-five patients with characteristics outlined in the British Hypertension Society protocol were recruited among those attending our out-patient clinic. Sequential readings were taken for the main validation test. Outcome was classified according to the British Hypertension Society criteria, which are based on four zones of accuracy differing from the mercury standard by 5, 10 and 15 mmHg, or more. RESULTS: The mean blood pressure difference (+ or -1 SD) between device and observers was 0.4 mmHg (SD 7.7) for systolic blood pressure and 0.3 mmHg (SD 8.2) for diastolic blood pressure. Overall, 96% (observer 1) and 95% (observer 2) of readings between device and observers differed by 15 mmHg or less for both systolic and diastolic blood pressure. The device achieved a grade A for both systolic and diastolic blood pressure. CONCLUSIONS: This study shows that the A&D UA-705 device satisfies the British Hypertension Society standard for accuracy by achieving a grade A for both systolic and diastolic blood pressure.