Curvas de referencia de presión arterial según edad y altitud de residencia en adultos peruanos

Effect on blood pressure of combined inhibition of endothelin-converting enzyme and neutral endopeptidase with daglutril in patients with type 2 diabetes who have albuminuria: a randomised, crossover, double-blind, placebo-controlled trial

Lifestyle modification continues to be an important initial strategy in both the prevention and treatment of hypertension as recommended in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Clinical trials have documented that weight loss, sodium restriction, alcohol restriction, and increasing physical activity may help prevent, as well as treat, hypertension. While the effects of dietary macronutrients on blood pressure (BP) have not been as well studied, the most effective dietary approach to lowering BP involves a diet rich in fruits, vegetables, and lowfat dairy products, i.e., the Dietary Approaches to Stop Hypertension (DASH) diet. The DASH diet involves a modest increase in dietary animal and vegetable protein. Other clinical trials studying dietary protein intake and reduction in BP have produced conflicting results. He and colleagues conducted a randomized, double-blind, multicenter, controlled trial of a diet rich in soybean protein compared to a complex carbohydrate control diet in 302 adult Chinese subjects with stage 1 hypertension (systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or both) or prehypertension (systolic BP 120 mm Hg-139 mm Hg; diastolic BP 80 mm Hg-89 mm Hg) from three communities in the People's Republic of China. Demographic and dietary characteristics were similar in the three communities and were made up of men and women 35–64 years of age. Trial participants had not been on any antihypertensive medication for at least 2 months and had no underlying cardiovascular or renal disease or diabetes. Of interest, they had restricted their alcohol use to no more than 21 drinks per week. Subjects were randomized to 12 weeks of supplementation with 40 g/d of isolated soybean protein or 40 g of complex carbohydrate from wheat, both given in the form of cookies. The daily nutritional content of the cookies was similar except for their dietary protein content (49 g vs. 12.9 g) and carbohydrate content (64.8 g vs. 95.3 g), soybean and control groups, respectively. The daily portion of the soybean protein cookies contained 76.4 mg of total isoflavone. On entry, average systolic BP was between 130-159 mm Hg (mean 135 mm Hg) and average diastolic BP was between 80-99 mm Hg (mean 84.7 mm Hg) based on an average of nine readings (three observations at each of three screening visits). BP readings were obtained at follow-up visits 6 and 12 weeks after randomization. Trained research staff conducted a 24-hour dietary recall at the screening visit, the 6-week visit, and the 12-week visit. A 24-hour urine specimen was obtained at the same time periods to measure urinary sodium and potassium. Side effects (15 items) were evaluated using a standard questionnaire at the 12-week follow-up visit. The primary outcome was the net difference in change (final follow-up - baseline) of systolic and diastolic BP between the study groups. After 12 weeks, approximately 90% of both study groups completed the study and 92% of both groups adhered to their dietary intervention. Urinary excretion of sodium decreased and urinary excretion of potassium increased to a similar extent in both groups with no significant differences in body weight. There was a significant reduction in both systolic (−4.3 mm Hg) and diastolic (−2.76 mm Hg) BP in subjects on the soy protein supplement. Differences between the treatment groups were greater among subjects with hypertension (−7.88 mm Hg systolic and −5.27 mm Hg diastolic) than among people with prehypertension (−2.34 mm Hg systolic and −1.28 mm Hg diastolic). Favorable effects on BP reduction occurred in both men and women, in younger and older subjects, as well as in obese and nonobese individuals. Rates of adverse effects did not differ between the groups. In this short-term, 12-week study, increased intake of vegetable protein, in the form of soybean supplementation, resulted in reductions in both systolic and diastolic BP. Whether this favorable effect on BP is due to the vegetable protein or isoflavone content in soybeans remains unclear.—He J, Gu D, Wu X, et al. Effect of soybean protein on blood pressure: a randomized, controlled trial. Ann Intern Med. 2005;143:l-9. While observational studies have suggested that soybean protein supplementation lowers BP, several small clinical trials have previously reported inconsistent findings. Most clinical trials that have evaluated the effects of an increased intake of dietary protein on BP have had a small sample size, did not systematically evaluate BP, and did not use changes in BP as the primary outcome of interest. The present study, with the largest sample size and several well-executed measurements of BP, suggests that soybean supplementation reduces both systolic and diastolic BP. This effect was consistent regardless of gender, age, and body weight. The effect noted was greatest in people with hypertension, with less of an effect in prehypertensive individuals. While not powered to evaluate subgroups, this study suggests that soybean protein supplementation is more important for treating hypertension than for preventing it. This was not a forced feeding study like the DASH trial. By using 24-hour dietary recall, the authors found that subjects increased their dietary protein intake by only 26 g, less than the targeted 40 g. It also remains unclear whether the favorable effect on BP reduction is due to soybean protein or isoflavone content: this needs to be evaluated in future trials. In addition, since there has been an association between soy protein and bladder cancer in two cohort studies, this association needs further clarification before we can promote this recommendation. Further research is necessary to determine the mechanistic benefits of soybean protein supplementation on BP reduction. Proposed mechanisms include the vasodilatory protein components of soybean; the soybean associated dietary increase in arginine, the metabolic precursor of NO; or an improvement in insulin sensitivity. Although recommended as first-line therapy in the treatment of hypertension, physicians have remained pessimistic over the ability of lifestyle modification, including nutritional intervention, to effectively prevent as well as treat hypertension. The current findings suggest that increasing consumption of soybean protein may be useful in treating hypertension. As dietary protein in China is mainly derived from plant foods (not from animal foods as in the United States) and with the average dietary protein intake of 69 g/d in this Chinese study (whereas the average dietary protein intake in the United States is 79 g/d [National Health and Nutrition Examination Survey (NHANES III)]), the authors appropriately wonder whether their study findings can directly apply to the US population. Before we recommend increased soybean protein intake as a means of treating and preventing hypertension, further evidence of safety, feasibility, and efficacy in this country is required. At present, we should continue to recommend the DASH diet, providing an increased amount of both animal and vegetable protein in our diet. Ginseng is a commonly used herbal supplement that grows in the temperate regions of Asia and North America. Currently, about 4.5% of Americans use it. Like many supplements, the safety and efficacy of ginseng is not well studied in individuals with hypertension. Ginseng's exact mechanism of action is unknown. Previous reports have suggested that ginseng may increase blood pressure (BP), while other reports have shown a neutral effect. The ginseng currently used is often a blend of several species of ginseng, which vary in their ginsenoside content, the component believed to be responsible for its effect on blood pressure. The two most consumed species in the United States are Panax ginseng and Panax quinquefolius, also known as North American ginseng (NAG). In the current clinical trial, Canadian investigators examined the acute effects of NAG on BP in individuals with hypertension. Nineteen individuals, aged 18-75 years, with hypertension (defined as systolic BP >140 mm Hg or diastolic BP >90 mm Hg) at each of three separate prestudy visits or on antihypertensive medications provided informed consent. Exclusion criteria included secondary hypertension, diabetes mellitus, kidney or liver disease, unstable angina, change in body weight of >2.2 kg between visits, or use of any herbal supplements in the previous 2 months or during the study. Sixteen participants (12 men and 4 women, mean age of 61 years, with a mean BP 132/83 mm Hg) completed the study. Thirteen of the 16 individuals were on antihypertensive therapy on entry. Each participant, serving as their own control, was randomized in a double-blind fashion to six different batches of 3-mg NAG and two identical 3-mg corn starch placebo tablets. The batches of NAG were selected by the Ontario Ginseng Growers Association to represent the spectrum of NAG available on the market; they were carefully examined for quality. Each NAG root batch (or placebo) was ground into a powder and packed into identical capsules by a technician blinded to study allocation. On eight consecutive mornings, participants arrived at the study center in a fasting state, did not take their prescribed antihypertensive medications, and were fitted with an ambulatory BP monitor. Office and ambulatory BP readings (5-minute intervals for 30 minutes using SpaceLabs 90207, SpaceLabs Medical, Inc., Issaquah, Washington) were taken at baseline and 60 minutes after administration of study medication (corresponding to peak plasma concentrations of NAG). For each batch of NAG and placebo, the post-treatment change in systolic BP, diastolic BP, and pulse pressure per individual relative to baseline were calculated at 10-minute intervals and averaged. In addition, each batch of NAG had its ginsenoside content determined by high-performance liquid chromatography. All six NAG samples showed a comparable content of ginsenosides. No significant differences in mean systolic BP, diastolic BP, or pulse pressure at each of the 10-minute intervals or over the entire 160-minute post-treatment period were seen between the six individual NAG and placebo treatments. Taken together, and compared with placebo, the NAG treatments increased systolic and diastolic BP slightly at 140 and 160 minutes, respectively, but decreased diastolic BP slightly at 100 minutes. Overall, there was no significant difference between the average of the NAG batches and placebo on total post-treatment change in systolic BP, diastolic BP, and pulse pressure. The authors conclude that NAG exerts a neutral acute effect on BP in hypertensive individuals.—Stavro PM, Woo M, Heim TF, et al. North American ginseng exerts a neutral effect on blood pressure in individuals with hypertension. Hypertension. 2005;46:406-411. Roughly one third of adults use neutraceuticals, and 15 million Americans use them together with conventional medicines. Their use is of tremendous importance to the hypertension community. A recent prevalence study from the Mayo Clinic found that 61% of people 18 years of age and older had used a neutraceutical over the past year. These “dietary supplements,” defined as a vitamin, mineral, herb, or other botanical, are excluded from the rigorous scientific evaluation that ensures both the safety and the effectiveness required of “drugs” presented before the FDA. These products are often promoted and accepted by the public to positively affect one's health, despite their lack of certainty for benefit. With sales of neutraceutical products increasing 25% per year in the United States, their influence on BP control continues to be of great importance. Nine million American adults use ginseng, and it continues to be popular among patients with hypertension. In many cases, its safety and efficacy is undocumented. One concern has been a lack of standardization of available preparations. In this evaluation, Canadian investigators working with the Ontario Ginseng Growers Association took great trouble to ensure that they were using a sample that represented the spectrum of what is currently available on the market. Even so, the study is limited to only one type of commonly used ginseng root, NAG. The other ginseng root commonly used, Panax ginseng, was not used in this trial, but a previous investigation by the same investigators demonstrated that in steamed form, Panax ginseng caused a modest decline in BP with acute administration. The authors postulate that perhaps the disparate effects on BP between the two species may be due to the presence of ginosenoside Rg3, which is found in Panax ginseng but not in NAG. As opposed to regulated prescription medications, the safety and efficacy of one formulation of an herbal supplement should not necessarily be extrapolated to other formulations that may vary considerably in active ingredient content. While this well-designed, clinical trial using ambulatory BP monitoring describes the acute effects of ginseng on BP, it is limited by its small sample size, low dosage used, lack of concomitant antihypertensive medication administration, and sole focus on the acute BP changes associated with a single dose of ginseng. While the available evidence suggests that patients with hypertension need not avoid either NAG or Panax ginseng due to concerns about acute BP elevation, further investigations will determine its safety and efficacy with chronic administration in hypertensive patients. At present, ginseng should not be recommended for individuals with hypertension.

Transient elevation of arterial blood pressure (BP) is frequent in acute ischemic stroke and may help to increase perfusion of tissue jeopardized by ischemia. If this is true, recanalization may eliminate the need for this BP elevation. We analyzed BP in 149 patients with acute ischemic stroke on admission to the hospital and 1 and 12 hours after intraarterial thrombolysis. BP values of patients with adequate recanalization were compared with BP values of patients with inadequate recanalization. Recanalization was determined on cerebral arteriography after thrombolysis using thrombolysis in myocardial infarction grades. Systolic, mean, and diastolic arterial BP decreased significantly from admission to 12 hours after thrombolysis in all patients (P<0.001). Before thrombolysis, patients with adequate and inadequate recanalization showed equal systolic (147.4 and 148.0 mm Hg), mean (102.1 and 104.1 mm Hg), and diastolic (79.5 and 82.1 mm Hg) BP values. Twelve hours after thrombolysis, patients with adequate recanalization had lower values than those with inadequate recanalization (systolic BP, 130 versus 139.9 mm Hg; mean BP, 86.8 versus 92.2 mm Hg; and diastolic, BP 65.2 versus 68.3 mm Hg). Two-way repeated ANOVA analysis showed a significant group x time interaction for systolic BP, indicating a larger systolic BP decrease when recanalization succeeded (P=0.019). The course of elevated systolic but not diastolic BP after acute ischemic stroke was found to be inversely associated with the degree of vessel recanalization. When recanalization failed, systolic BP remained elevated longer than when it succeeded.

If the restoration of sinus rhythm (SR) by electrical cardioversion (ECV) in patients with atrial fibrillation (AF) may have a role in inducing blood pressure (BP) changes over time, it remains a largely unaddressed topic. This appears surprising in relation to the fact that AF and systemic hypertension constitute two closely related clinical entities. Indeed, AF is the most common sustained cardiac arrhythmia and, in turn, hypertension is the most common comorbid condition associated with AF.1 Moreover, the risk of stroke, heart failure, and cardiovascular mortality in patients with both AF and hypertension is markedly greater when compared with either condition alone. AF is a rapidly growing public health and socio-economic burden worldwide. It has been calculated that the total number of individuals with clinically diagnosed AF could increase from around 30-35 million (estimated data in 2010) to over 60-70 million over the next 30 years, as a result of demographic changes related to the progressive increase in life expectancy and the rising prevalence of risk factors for AF such as hypertension, diabetes mellitus, obesity, and chronic kidney disease.2 The clinical relevance of hypertension as a primary risk factor for AF in the general population has been clearly demonstrated by the Framingham Study researchers 25 years ago.3 In an analysis of 4731 individuals free of AF at entry, hypertension, defined as taking BP lowering drugs or a systolic BP of 160 mm Hg or greater, was associated with a 50% higher risk of incident AF in men and a 40% higher risk in women. Recent findings from the Clinical Practice Research Datalink (CPRD), a primary care database representative of the UK population in terms of age, sex, and ethnicity, examining 4.3 million individuals and 128 468 incident AF events, showed that systolic and diastolic BP were positively related to risk of AF.4 A 20-mm Hg higher usual systolic BP was associated with a higher risk of AF [hazard ratio (HR) 1.21]. In the Women's Health Study, including 34 221 participants free of prevalent cardiovascular disease at baseline, clinic BP was strongly associated with incident AF, and systolic BP was a better predictor than diastolic BP. Of note, systolic BP levels within the non-hypertensive range were independently associated with incident AF even after taking into account BP changes over time.5 It is worth noting that information on the contribution of ambulatory BP monitoring (ABPM) components to the risk of developing AF is scanty. Data collected from 2776 subjects randomly recruited from the general population in five European countries showed that each standard deviation (SD) increase in baseline 24-hour, daytime and nighttime systolic BP was associated with a 27%, 22%, and 20% significant increase in the risk for incident AF, respectively.6 In the Oulu Project Elucidating Risk of Atherosclerosis (OPERA), the value of ABPM components in predicting the long-term risk of AF was assessed in 903 subjects with or without hypertension aged 40 to 59 years.7 Among the baseline ABPM components, the nighttime mean systolic BP turned out to be an independent predictor of the occurrence of AF (HR = 1.07 per every 5 mm Hg increase). A mounting body of evidence suggests that reductions in BP can lower the risk of developing new AF. There is debate about the hypothesis that more intensive treatment aimed at greater reduction of BP can have an additional positive effect in preventing new-onset AF. The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study examined whether lower achieved systolic BP (≤130 mm Hg) was associated with a lower incidence of AF compared with standard systolic BP control (131-141 mm Hg) and less-adequate control (systolic BP ≥142 mm Hg) in 8831 hypertensive patients with left ventricular hypertrophy.8 Compared to patients with in-treatment SBP ≥142 mm Hg, those with in-treatment SBP ≤130 mm Hg had a 40% lower risk of incident AF and those with in-treatment SBP of 131 to 141 mm Hg with a 24% lower risk, respectively. Finally, a number of studies indicated that a sub-optimal treatment of elevated BP in patients with AF is associated with a markedly higher risk of stroke and cardiac events. The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial reported that elevated BP measurements at any point during the trial were associated with a subsequent 50% increase in risk of stroke or systemic embolism (HR, 1.53).9 In this complex scenario, the study of Olbers et al offers a new piece of evidence on BP changes following the SR restoration obtained with ECV.10 In their retrospective analysis, including 487 patients with AF, who underwent elective ECV, a recovery of an SR was observed in 59.3% (n = 289) of the cases after one week. In the group of patients converted to SR, there was a significant increase in systolic BP (from 129 ± 17 mm Hg to 137 ± 18 mm Hg, P < 0.001), with a decrease in diastolic BP (from 82 ± 9 mm Hg to 79 ± 10 mm Hg, P < 0.01). In contrast, no significant changes in both systolic and diastolic were found in the group of 198 patients with persistent or relapsing AF. Before commenting the strengths and limitations of the paper by Olbers et al,10 it may be useful to briefly summarize the findings provided by previous studies on this topic. In a paper aimed to assess changes in exercise capacity, echocardiographic parameters, and plasma atrial natriuretic peptide concentrations in 42 patients with persistent AF, before and 30 days after ECV there were no statistical differences in office BP between the two groups with and without successful procedure.11 No statistically significant change in daily BP, as assessed by ABPM performed before and after ECV, was found by Olsen et al12 in a group of 42 AF patients. In particular, they failed to demonstrate differences between the patients who achieved SR and those who maintained AF. In a further small ABP-based study including 18 hypertensive patients with successful ECV, the restoration of SR resulted in a sustained decrease in diastolic and mean BP one day after ECV and this trend persisted after 1-month of follow-up.13 A further investigation focused on the impact of ECV on sublingual microcirculation by side-stream darkfield imaging in 14 patients converted from AF to SR and showed a significant decrease in systolic and diastolic BP after the procedure.14 A retrospective study by Ramirez et al,15 encompassing a total of 159 hypertensive patients with AF, suggested that successful catheter ablation was associated with a reduction in BP, whereas an opposite trend was observed after 1 year of follow-up in patients with failed ablation. More recently, Maselli et al demonstrated that office systolic BP increased significantly (+5 mm Hg) in 63 patients after thirty days from the recovery of SR by ECV, while, on the contrary diastolic BP showed an opposite tendency (−5 mm Hg).16 A subsequent study by the same group, in which 54 hypertensive patients underwent ABPM the day before and one month after cardioversion, documented that patients maintaining a SR at follow-up (n = 34) had significantly higher 24-hour, nighttime and daytime systolic BP, and significantly lower 24-hour, daytime, and nighttime diastolic BP.17 Whereas no significant BP changes were observed in patients with persistent or recurrent AF at follow-up (n = 20). Overall, these findings do not allow conclusions to be drawn about the effects of successful ECV on BP. This is clearly related to the significant differences between the various studies in terms of numerosity, clinical features of patients, follow-up duration, and methods of BP measurement. Many pathophysiological mechanisms can be invoked to explain the reduction of BP associated with restoration of SR. AF is associated with an increase in sympathetic nerve activity resulting in vascular and renal changes that promote hypertension. Furthermore, numerous studies have shown that AF is associated with activation of the renin-angiotensin-aldosterone system (RAAS), endothelial dysfunction and depressed nitric oxide bioavailability. Indeed, it has been reported that a successful ECV in patients with persistent AF is accompanied by a marked reduction in aldosterone levels.18 On the other hand, studies that have shown an increase in systolic pressure have called for several hemodynamic changes following ECV (ie, an increase of the ejection fraction, the duration of the diastolic phase, and the cardiac output) in support of their results. The above-mentioned changes may be particularly relevant in AF patients with ventricular dysfunction and marked irregularity of the ventricular response. The study by Olbers et al, showing a clear-cut increase of the systolic BP values and consequently of the prevalence uncontrolled hypertensive (+40%) after restoration of SR, has the merit of being based on the largest series published so far. A very critical point in this type of study represented by variations in therapy during follow-up was appropriately addressed by the authors analyzing the data of the subgroup in which therapy after ECV was not changed (ie, 371 out 487 patients). Even eliminating the confounding effect of therapeutic modifications, the increase in systolic BP remained clinically relevant and similar to that observed in the total sample. An additional interesting observation is that not only hypertensive patients but also those without a pre-existing diagnosis of hypertension exhibited significant BP increments after ECV. Although the information provided by this study is based on a retrospective design, a short duration of follow-up (reduction of sympathetic and RAAS activation may take longer than a week) and supine BP measurement has the great value to stress the issue of BP control in AF hypertensive patients submitted to ECV. In conclusion, the findings from the Olbers study suggest that restoration of SR in individuals with FA may require a re-evaluation of antihypertensive therapy in order to reduce the high cardiovascular risk associated with insufficient BP control in this setting;19 but, at the same time, they indicate that further investigations are needed to clarify the controversial aspects of this important topic. The authors report no conflicts of interest.

Antihypertensive drug therapy is a major modality of cardiovascular (CV) disease prevention, especially for stroke, congestive heart failure, and renal insufficiency. Coronary risk is also consistently prevented by antihypertensive treatment, but to a lesser extent.1–4 The Prime Study2 has shown that drug-induced blood pressure (BP) reduction in hypertensive subjects is associated with a significant decrease of coronary risk. However, when treated and untreated subjects are compared, at any given value of systolic BP (SBP), this risk remains higher in treated than in untreated subjects, suggesting the persistence of residual coronary complications. Results of therapeutic trials also indicate that coronary risk is associated with a particular hemodynamic pattern in treated hypertensive subjects.3 Although diastolic BP (DBP) is significantly lowered by drug treatment to <90 mm Hg (80% of the patients), SBP remains above 140 mm Hg in 60%, indicating an increase of pulse pressure (PP), which is the difference between SBP and DBP.4 It is widely accepted that SBP and PP rise sharply with age and that this increase is a major manifestation of vascular aging and stiffening, which are now considered major predictors of CV risk, independent of the mean BP (MBP) level.4 The purpose of this review is to analyze the mechanism(s) of SBP in untreated and chronically treated hypertensive subjects and to determine which pathophysiological factors are susceptible to attenuating consistently coronary and CV complications in hypertensive populations. Ventricular ejection in humans is associated with 2 principal events. First, the coronary circulation is transiently interrupted, as the principal consequence of cardiac contraction, and, second, an acute shock of stroke volume against the aortic wall is observed (Figure 1). Then, the BP curve may be considered as a wave, which travels along the arterial tree at a given speed, the pulse wave velocity (PWV). …

This clinical advisory statement from the Coordinating Committee of the National High Blood Pressure Education Program is intended to advance and clarify the recommendations of the Sixth Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI, 1997).1 The advisory addresses several interrelated issues about blood pressure (BP) that affect people approaching the later decades of life. On the basis of the wealth of currently available evidence, the committee now recommends a major paradigm shift in urging that systolic BP become the major criterion for diagnosis, staging, and therapeutic management of hypertension, particularly in middle-aged and older Americans. Several lines of strong evidence support the initiative to emphasize systolic BP. Pathophysiologically, there are strong associations among aging, increased stiffness of large arteries, increased systolic BP, increased pulse pressure, and the prevalence of cardiac and vascular disease. Epidemiologically, isolated systolic hypertension is the most common form of hypertension and is present in approximately two thirds of hypertensive individuals >60 years of age. Diagnostically, classification and staging of hypertension are more precise when systolic rather than diastolic BP is used as the principal criterion. Risk stratification for major complications of hypertension (stroke, myocardial infarction, heart failure, and kidney failure) is actually confounded by the use of diastolic BP; in older people with systolic hypertension, diastolic BP is inversely related to cardiovascular risk. Clinical benefits of treatment of isolated systolic hypertension include reductions in stroke, myocardial infarction, heart failure, kidney failure, and overall cardiovascular disease morbidity and mortality. Currently, only 1 in 4 Americans with hypertension falls below JNC VI–recommended values of 140/90 mm Hg in uncomplicated hypertension or 130/85 mm Hg in individuals with kidney disease or diabetes. Hypertension control rates are poorest in older people, primarily as a result of inadequate …

Objective: End–digit preference is common in blood pressure (BP) measurement, but there are no data available on end–digit preference in China. The purpose of this study was to investigate the frequency of end–digit preference in Chinese hospitalized patients and to explore its risk factors. Methods: We used systematic sampling to investigate the BP values and related characteristics in records from Chinese patients hospitalized at a university–affiliated hospital in Shanghai, China. Data were collected from January to December 2010. Logistic regression models were created to analyze the relationship between potential risk factors and zero end digit in recorded BP values. Results: Of all 4511 patient records, 57.1% of patients were male. The mean age was 55.1 years (standard deviation [SD], 15.4 years). When admitted, the mean BP values were 124.6 mm Hg (SD, 14.3 mm Hg) for systolic blood pressure (SBP) and 77.5 mm Hg (SD, 8.6 mm Hg) for diastolic blood pressure (DBP). 81.8% and 81.2% of SBP and DBP values had an end digit of zero. 7.7% and 9.6% of SBP and DBP values had an end digit of “5.” In the logistic regression analyses, female sex (odds ratio [OR], 1.34 for SBP, 1.24 for DBP), admission to a surgical department (OR, 2.04 for SBP, 1.88 for DBP), admission heart rate of ≥ 80 bpm (OR, 1.41 for SBP, 1.61 for DBP), and not having a history of hypertension (OR, 1.41 for SBP, 1.33 for DBP) were related to a high risk of having SBP and DBP values with a zero end digit. Patients with SBP values of ≥ 140 mm Hg had a high risk of having a zero end digit in SBP values (OR, 1.33) and a low risk of having a zero end digit in DBP values (OR, 0.67). Patients whose DBP values were ≥ 90 mm Hg had a high risk of having a zero end digit in DBP values (OR, 2.49). Conclusion: The zero end–digit preference in recorded BP values of hospitalized patients in China was strong. Patients' sex, admission to a surgical department, admission heart rate, history of hypertension, and SBP and DBP values were risk factors that influenced the preference for zero as the end–digit BP value.

Cardiovascular risk of systolic versus diastolic blood pressure in Western and non-Western countries

We compared the predictive power for a major adverse cardiovascular event (MACE) of four home blood pressure (BP) indices (systolic BP, diastolic BP, mean BP, and pulse pressure (PP)) obtained at baseline before treatment and during the on-treatment follow-up period in 3147 patients with essential hypertension (women: 50.1%, mean age: 59.5 years). Associations between MACE and each index were determined using Cox proportional hazard models and the likelihood ratio (LR) test. During a median follow-up of 5.4 years, 46 patients experienced MACE, which was a composite of cardiovascular death, non-fatal stroke, and non-fatal myocardial infarction. The LR test showed that systolic, diastolic, and mean BP during follow-up was more closely associated with cardiovascular risk than the corresponding indices at baseline (LR χ2 for baseline versus follow-up: systolic BP, (6.0, P = 0.014) versus (11.3, P = 0.0008); diastolic BP, (0.4, P = 0.53) versus (12.4, P = 0.0004); mean BP, (3.2, P = 0.074) versus (15.0, P = 0.0001)), whereas neither PP at baseline nor that during follow-up was significantly associated with MACE risk. Among home BP indices during follow-up, mean BP further improved prediction models in which systolic or diastolic BP was already included (P ≤ 0.042), but neither systolic nor diastolic BP improved models with mean BP (P = 0.80). In addition to home systolic and diastolic BP, mean BP during follow-up period provides essential information in predicting future cardiovascular diseases, whereas its utilization should be further assessed by an intervention trial targeting mean BP levels.

After completing this article, readers should be able to: Few aspects of neonatal care have generated as much controversy as the assessment of blood pressure (BP) and need for treatment of perceived abnormalities of this physiologic variable. Familiarity with clinical situations in which BP may be low should allow anticipation of this common clinical problem and timely intervention when such treatment is necessary (Tables 1 and 2). In this article, we review factors that have been shown to have the greatest effect on BP.A direct reading from an indwelling arterial catheter represents the “gold standard” for measuring BP in the neonate, and this method should be used whenever possible. Obviously, arterial access may not always be available, and the ability to monitor BP noninvasively using an oscillometric technique represents a major advancement in neonatal care. The correlation between direct and indirect methods generally has been good. Disparities in results have been related to various factors, including inappropriate cuff width-to-arm ratio or problems with the arterial catheter-transducer system, such as air bubbles or clots. In general, indirect determinations are higher than those obtained directly, often by 3 to 5 mm Hg.The individual contributions of birthweight and gestational age to BP are difficult to delineate. Several groups of investigators have shown that BP at birth is higher in larger, more mature infants. There is evidence that small-for-gestational age infants have lower BPs than do larger babies of comparable gestational age, which suggests that birthweight per se may be more than a marker for increased maturity.Early studies involving large numbers of infants who had a wide range of birthweights and gestational ages demonstrated the significance of both of these variables. In a recent report of a large multicenter study conducted by the Philadelphia Neonatal Blood Pressure Study Group, systolic and diastolic blood pressures were significantly correlated with birthweight (Fig. 1) and gestational age (Fig. 2).Le Flore and associates studied 116 very low-birthweight (VLBW) neonates during the first 72 hours after birth. Following multiple linear regression, both gestational age and birthweight were primary variables predicting mean blood pressure (MBP) during this period. However, gestational age explained more of the variance in MBP during the first 24 hours, with each additional week of gestation increasing MBP by 1.4 mm Hg. Neonates of 24 to 25 weeks’ gestation had an initial MBP of 27±4 mm Hg versus 39±7 mm Hg for neonates at 32 to 33 weeks’ gestation (P≤0.01) (Fig. 3). In contrast, birthweight explained more of the variance in MBP between 25 hours and 72 hours after birth, with each increase of 100 g associated with an increase in MBP of 1.0 mm Hg. The Joint Working Group of the British Association of Perinatal Medicine has recommended that MBP (in mm Hg) be maintained at or above the gestational age of the infant (in weeks). Further investigation is required to establish the safety and efficacy of this approach.As alluded to previously (Fig. 3), MBP increases postnatally in VLBW neonates regardless of gestational age. Zubrow and associates found a similar relationship between BP and postnatal age in infants whose birthweights were 750 to 4,000 g and gestational ages were 22 to 42 weeks (Fig. 4). When the effect of postnatal age on BP was analyzed over a longer period of time, systolic BP was approximately 30 mm Hg higher at the 4-month age-adjusted outpatient examination compared with values at 7 days after birth.The association between advancing birthweight, gestational age, and postnatal age and increases in BP is not understood completely. A discussion of the complex neural, hormonal, and vascular mechanisms that control BP is beyond the scope of this article, but their maturation is a significant consideration. Anatomic relationships may play a role, and decreases in right ventricular pressure after birth may result in improved left ventricular shape and function. Also, it has been shown that urinary prostaglandin E2 and plasma 6-keto-prostaglandin F1alpha (stable metabolite of prostacyclin) decrease during the first 3 postnatal days in preterm neonates. This could result in a rise in vascular tone and increased vascular reactivity. More recently, it has been reported that vascular smooth muscle protein expression and contractility demonstrate functional maturation during development. Thus, the rise in BP during the fetal-neonatal transition may reflect decreases in the activity and synthesis of vasodilators, which are critical to fetal survival, as well as intrinsic changes in vascular smooth muscle function occurring prior to and following birth, both of which appear to be developmentally regulated.Significant hypotension in the neonate can be a reflection of prenatal, intrapartum, or postnatal hemorrhage (Table 1). Fetomaternal, twin-twin, intracranial, subgaleal, and hepatic hemorrhages are the most common types of significant blood loss. Adrenal hemorrhage is a very rare (but reported) cause of severe neonatal hypotension, although the mechanism of subsequent blood pressure instability may be more associated with adrenocortical derangement than significant blood loss. Hemorrhage should be considered in any hypotensive neonate, but it is important to note that the initial physiologic response involves the release of vasoactive substances, such as catecholamines and arginine vasopressin. Hypotension may be a relatively late finding that suggests the presence of acute blood loss. The pre-equilibration hemoglobin and hematocrit values also may be misleading following blood loss.Infusion of cortisol into the sheep fetus results in increased arterial pressure. Several reports have suggested that neonatal BP is higher in preterm infants whose mothers received antenatal steroids to hasten fetal lung maturity. This finding would not be unexpected because previous studies have suggested that sick preterm neonates may have relative adrenocorticosteroid insufficiency. Furthermore, successful treatment with hydrocortisone or dexamethasone, administered because of hypotension refractory to conventional therapies, has been documented.In one study, neonates whose mothers received dexamethasone had higher MBPs during the first 3 days after birth, but this relationship was less clear when adjustment for birthweight was made. After this adjustment, a significant difference in BP was noted only 2 hours following initial treatment with exogenous surfactant. A subsequent study investigated the amount of BP support required by extremely preterm infants (23 to 27 weeks’ gestation) whose mothers did or did not receive antenatal steroids. Infants not exposed to antenatal steroids had lower MBPs from 16 to 48 hours after birth. Furthermore, the use of dopamine was increased in the infants not exposed to antenatal steroids. The reduction in severe intraventricular hemorrhage observed in infants whose mothers received antenatal steroids has been linked to normal BP in those infants. In another study, MBP during the first 24 hours after birth was increased in VLBW infants whose mothers received antenatal steroids, and volume expansion and vasopressor support were decreased in those infants.Conversely, LeFlore and associates reported no differences in BPs among 116 VLBW neonates whose mothers did or did not receive antenatal steroids, and similar results were obtained in another study. Other investigators have reported a tendency for higher mean BP in infants weighing at least 1,000 g whose mothers received antenatal steroids but a tendency for lower MBP in infants weighing less than 1,000 g who were exposed to antenatal steroids. Leviton and colleagues found no difference in the incidence of lowest MBP less than 30 mm Hg in infants whose mothers did or did not receive a complete course of antenatal glucocorticoid prophylaxis.Obviously, further investigation is required to determine the relationship between antenatal steroids and BP. Perhaps in the subset of preterm infants who truly have relative adrenal insufficiency, antenatal steroids may enhance neonatal cardiovascular stability and raise BP, while antenatal steroids have little or no effect on BP in those who have adequate adrenal function.The effect of route of delivery on BP in the neonate has been studied extensively. Several studies in term neonates have indicated that BP in vaginally delivered infants is higher than in those delivered by cesarean section. In general, these studies have attributed the higher BP in the former group to increased catecholamine concentrations and cord blood arginine vasopressin and adrenocorticotropin hormone levels. However, among VLBW infants, blood pressures were similar in infants delivered vaginally and those delivered by cesarean section. Likewise, in the study by Zubrow and associates, which included 106 infants of 32 weeks’ gestational age or younger, stepwise multiple linear regression analysis did not identify route of delivery as a significant determinant of BP variation. Breech delivery has been associated with BP in the lower range of normal. The volume of placental transfusion (as well as postnatal transfusion) also may affect BP.The classic studies of Dawes in newborn monkeys demonstrated that BP initially rises with ongoing asphyxia, but after 5 minutes, it decreases progressively. As emphasized by the American Academy of Pediatrics/American Heart Association Committee on Neonatal Resuscitation, many infants who have birth depression and possibly some degree of hypotension respond to effective positive-pressure ventilation and do not require specific measures to raise BP (see accompanying article on treatment of hypotension).Circulatory changes resulting from apnea in the neonate have been summarized by Miller and Martin. The initial decrease in heart rate is accompanied by a rise in pulse pressure, usually due to an increase in systolic pressure. These events presumably result from increased filling volume associated with bradycardia, which leads to enhanced stroke volume in accordance with Starling’s law. As the severity of apnea and bradycardia increases, BP may decrease, along with a fall in cerebral blood flow velocity. Thus, during prolonged apnea, cerebral perfusion may decrease significantly, placing the infant at risk for brain injury.Infants who have severe respiratory distress syndrome (RDS) may have lower BPs than those observed in healthy preterm neonates or infants who have less severe RDS. An association in infants who have RDS between marked fluctuations in arterial BP and fluctuating cerebral blood-flow velocity has been demonstrated. Also, an association has been reported between acute hypocarbia and marked systemic hypotension.Three aspects of respiratory management in preterm neonates have been shown to affect BP: 1) use of increased airway pressures, given either by constant positive airway pressure (CPAP) or intermittent mandatory ventilation; 2) suctioning of the airway, occasionally accompanied by a fall in diastolic pressure; and 3) instillation of an exogenous surfactant preparation into the airway. Although a number of studies in animals and humans have shown no effect of positive end-expiratory pressure or CPAP on BP, Kluckow and Evans observed a highly significant negative influence of mean airway pressure on MBP in preterm neonates requiring mechanical ventilation. BP fluctuations during mechanical ventilation may be decreased through the use of various methods of synchronized mechanical ventilation.Perlman and Volpe measured arterial BP, cerebral blood-flow velocity, and intracranial pressure in 35 intubated preterm neonates undergoing routine suctioning. MBP increased during suctioning in all but one patient, and these investigators concluded that the observed increases in cerebral blood-flow velocity and intracranial pressure were directly related to the increased blood pressure. Perry and colleagues reported an association between systolic BP above a “stability boundary” and increased periventricular-intraventricular hemorrhage, with BP elevations related temporally to suctioning. In addition to suctioning, BP response to various care procedures, including chest auscultation and physiotherapy, mouth rinsing, diaper changing, and nasogastric feeding, have been studied, and in general, BP responses were biphasic, with a decrease in BP followed by a greater and longer lasting increase.Numerous investigators have studied the physiologic effects of surfactant instillation in neonates, and differences in these reports may be due to dosing or technique of administration. In most studies, any effects on BP were transient. There may be greater hemodynamic effects associated with natural surfactant preparations, perhaps related to their generally more rapid pulmonary effects compared with artificial surfactant preparations.Studies of patent ductus arteriosus (PDA) in animals and preterm human neonates generally have shown significant decreases in diastolic BP. In one study, investigators noted that a diastolic BP of less than 28 mm Hg suggested the presence of PDA, although it is apparent from numerous studies that many normal VLBW neonates actually have mean BPs lower than 28 mm Hg.Among infants whose birthweights were 1,000 to 1,500 g, Evans and Moorcraft found similar BPs in the PDA and nonPDA groups. However, in those whose birthweights were less than 1,000 g, mean systolic and diastolic BPs were lower in infants who had PDA compared with those who did not. Furthermore, these hemodynanic effects could be demonstrated well before the PDA became clinically apparent. These authors cautioned against the use of volume expanders or inotopic agents in this population because these treatments might be counterproductive if the cause of the hypotension is a hemodynamically significant but clinically silent PDA. Furthermore, volume expansion appears to be a risk factor for the development of symptomatic PDA in VLBW neonates. It is apparent that problems with low BP related to PDA, especially diastolic BP, may result in inadequate perfusion of vital organs because of the “vascular steal” phenomenon. Optimum management of this clinical problem, of course, is directed at closure of the PDA rather than increasing the BP by other means.Neonatal sepsis is a common problem that can be devastating in both preterm and term neonates. The complicated pathophysiology of neonatal sepsis involves activation or release of numerous inflammatory and vasoactive substances, and hypotension can be a relatively late finding. The resulting effect on the cardiovascular system can be vasoconstriction, as is seen frequently in term and postterm septic neonates who have pulmonary hypertension or peripheral vasodilation with accompanying cardiomyopathy resulting in profound systemic hypotension (see accompanying article on treatment of hypotension). Necrotizing enterocolitis, which often accompanies sepsis, continues to be a common problem in the neonatal intensive care unit, and neonates who have moderate-to-severe disease very frequently are hypotensive.Maternal smoking may be associated with increases in both systolic and diastolic BP in the neonate, and a direct relationship between neonatal BP and the number of cigarettes smoked has been shown. This effect may persist for at least 12 months. Although maternal hypertension may be a factor associated with higher neonatal BP, this is not reported consistently. Cocaine exposure in utero has been shown to be associated with increased BP on the first day after birth in term neonates, and increased circulating catecholamine concentrations have been demonstrated. Mean arterial pressure was unchanged, but arterial pressure variability was decreased with both pancuronium and pethidine (meperidine). Fentanyl and midazolam may cause hypotension in neonates. Numerous studies have demonstrated that BP may increase and decrease with pneumothorax. Seizure activity may have variable effects on blood pressure. Increased neonatal BP has been documented in infants who have chronic lung disease and receive dexamethasone therapy.The smallest, least mature infants have lower BPs than infants who are larger and more mature. The effect of antenatal steroids, given to the mother when preterm delivery is anticipated, is controversial. Maternal smoking and route of delivery are perinatal factors that can influence neonatal BP. Sepsis and hemorrhage are associated with significant derangements in BP and always must be considered in a hypotensive neonate. PDA may be associated with a significant decrease in diastolic BP.

BACKGROUND: Laryngoscopy and tracheal intubation cause hypertension and tachycardia in anesthetized patients, which is undesirable, especially in patients with cardiovascular or neurosurgical diseases undergoing anesthesia. Various drug regimens and techniques have been used from time to time for attenuating the pressor response to laryngoscopy and tracheal intubation. The aim is to study, evaluate, and compare the efficacy of nitroglycerine (NTG) spray and 10% lignocaine spray in the attenuation of hemodynamic responses to laryngoscopy and endotracheal intubation and to observe and evaluate any side effects if any associated with the use of these drugs and their management. MATERIALS AND METHODS: This study was conducted on ninety patients under the American Society of Anesthesiologists (ASA) I and ASA II scheduled for elective surgeries. The patients were divided randomly into equal groups of 30 patients and received the following drugs before induction of general anesthesia: Group N-30 patients will be given NTG sublingual spray (2 puffs) 800 mcg 60s before laryngoscopy and group L-30 patients will be given lignocaine spray (2 puffs) 20 mg 60s before laryngoscopy. Hemodynamic variables were continuously recorded from baseline until 15 min after intubation and statistically analyzed. RESULTS: The demographic profile was comparable. The heart rate (HR) increased in both groups, although the increase in HR in the lignocaine group is higher than the increase in HR in NTG group. There was a significant difference in HR values immediately after intubation, 1, 3 min, and 5 min after intubation when the values were lower in group N, and the difference was statistically significant (P 0.05). There was a significant difference in systolic blood pressure (SBP) values immediately after intubation, 1, 3, and 5 min after intubation when the values were lower in group N and the difference was statistically significant (P 0.05). At 1, 3, and 5 min after intubation, the SBP values were significantly higher than baseline in the lignocaine group. However, there was a downward trend in SBP observed in the NTG group until 5 min after intubation, and it was statistically significant. There was a significant difference in diastolic blood pressure (DBP) values immediately after intubation, 1, 3 and 5 min after intubation when the values were lower in group N and the difference was statistically significant (P 0.05). The increase in mean DBP observed in the lignocaine spray group was statistically highly significant when compared to the increase in mean DBP in the NTG spray group. There was a significant difference in mean arterial pressure (MAP) values immediately after intubation, 1, 3 and 5 min after intubation when the values were lower in group N and the difference was statistically significant (P 0.05). NTG spray decreases the MAP more effectively as compared to lignocaine following laryngoscopy and endotracheal intubation. CONCLUSION: Based on our study, we conclude that: In lignocaine spray group patients who received a dose of 20 mg (2 puffs), there was a significant rise in HR, SBP, DBP, mean arterial blood pressure. In the NTG spray group patients who received a dose of 800 mcg (2 puffs), there is effective attenuation of the pressor response to laryngoscopy and intubation in normotensive ASA I–II patients. However, NTG is not able to attenuate the rise in HR due to reflex tachycardia due to vasodilation. Thus, it can be a better alternative in attenuating the hemodynamic responses to laryngoscopy and intubation.

The study by Protogerou et al.[1], published in this issue of the Journal of Hypertension, sheds light on the role of 24-h ambulatory aortic blood pressure (BP) as a correlate of target organ damage in hypertension. The main findings of the study are that both 24-h aortic and 24-h brachial BP are superior to conventional office BP measurements in predicting BP-related cardiac damage, and that 24-h ambulatory aortic BP is more closely associated with left ventricular hypertrophy than 24-h ambulatory brachial BP. On account of the results of this study, the authors suggest that the information on aortic BP derived from ambulatory BP monitoring (ABPM) improves the ability of regression models to detect the presence of left ventricular hypertrophy and to discriminate between individuals with and without left ventricular hypertrophy. There is a general consensus that 24-h ABPM is a better method for diagnosing hypertension and predicting BP-related cardiovascular risk than conventional office brachial BP measurements. Twenty-four-hour ambulatory BP (ABP) shows a stronger correlation with subclinical organ damage than office BP [2] and, more importantly, is a significantly better predictor of cardiovascular events [3–6]. The prognostic information offered by 24-h ABPM is independent of and incremental to that provided by office BP measurements [4–7]. In particular, ABP has the unique ability to provide information on 24-h average BP, on nocturnal BP and day–night BP changes, as well as on 24-h BP variability, which all provide independent prognostic information over and above that provided by office BP measurements [8–12]. The clinical relevance of ABPM is, therefore, clearly established in both treated and untreated hypertensive individuals [13]. The question is now whether the clinical value of ABPM might be further increased by incorporating information on ambulatory central BP. The possibility to combine the advantages of 24-h ABPM with those of central BP assessment by using devices which offer the estimate of central BP over the 24 h, in addition to the assessment of ambulatory brachial BP, sounds indeed attractive from both the clinical and experimental point of view. Central BP, that is, BP in the ascending aorta, is considered an important physiologic parameter as it reflects the hemodynamic relationship between the heart and the aorta, both in systole and in diastole. In the systolic phase, central BP represents the pressure against which the left ventricle has to eject blood during systolic contraction. Thus, central arterial pressure reflects both left ventricular stroke volume and afterload, defines cardiac work, and contributes to the development of left ventricular hypertrophy in hypertensive individuals. In the diastolic phase, central BP is a key determinant of the blood flow delivery to the myocardium. Thus, central SBP is an accurate marker of the actual pressure load imposed on the left ventricle and represents a more informative measurement, from a clinical perspective, than peripheral SBP, as shown by a few important clinical studies. Safar et al.[14] showed in end-stage renal disease patients undergoing hemodialysis that carotid pulse pressure (PP), directly measured by carotid tonometry, was a more powerful predictor of overall mortality than brachial PP. In that study, a lower peripheral BP amplification, that is, a greater central BP for any given level of brachial BP, was a significant predictor of all-cause (including cardiovascular) mortality, independent of age and other standard confounding factors. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) [15] showed a lower incidence of cardiovascular events among patients treated with the calcium-channel blocker amlodipine than with the β-blocker atenolol, with a small difference in the reduction of brachial SBP values between the treated groups. However, the Conduit Artery Functional Endpoint (CAFE) study [16], a substudy of the ASCOT, showed a lower central SBP and PP in the individuals randomized to receiving an amlodipine-based compared with those receiving a beta-blocker-based treatment, in spite of the similar values in brachial SBP. Therefore, the authors suggested that, in ASCOT, the greater reduction in cardiovascular events in the group randomized to amlodipine could be because of a greater effect of this drug in lowering central SBP. In a systematic review and meta-analysis, Vlachopoulos et al.[17] showed that central SBP and indices of central pulse amplification carry a significant predictive value for cardiovascular events and all-cause mortality. As a result of the anatomical proximity, the stress imposed on the heart, kidneys, and the brain is indeed driven more directly by aortic than by peripheral pressure [18]. Indeed, central BP has a closer relation to left ventricular mass and concentric geometry [19], and to carotid intima–media thickness and glomerular filtration rate [20], than peripheral BP. Despite all the above evidence, however, the 2013 European Society of Hypertension (ESH) and European Society of Cardiology (ESC) guidelines for the management of arterial hypertension [21] did not recommend the routine clinical measurement of central BP, with the exception of isolated systolic hypertension in the young, in whom the increase of SBP measured at the brachial artery may be because of a high amplification phenomenon, with normal values of central BP. There are important reasons why the ESH and ESC hypertension guidelines have been so cautious in recommending a more extensive clinical use of central BP. First, the additive predictive value of central BP beyond brachial BP was either marginal or not statistically significant in most studies [21]. Second, at least two serious methodological problems in relation to central BP measurement, both clearly highlighted in the study by Protogerou et al.[1], have not yet been satisfactorily addressed: the actual reliability of the methods used to measure central BP and the difficulties related to calibration of the tonometric pressure waveform to derive central BP. Central BP can be estimated either directly from the common carotid waveform or from the peripheral (radial or brachial) waveform with the use of a transfer function [22]. It has been widely documented that the shape of the pressure wave in the common carotid artery is comparable to that recorded in the ascending aorta [23–25]. Several studies comparing carotid tonometry with the invasive method concluded that applanation tonometry at the carotid artery level is a valuable tool for aortic pulse-wave recording and central (aortic) BP values assessment [24,25]. On the other hand, over the last few years, a large number of devices have been proposed aimed at assessing central BP using individual and generalized inverse transfer functions to reconstruct the aortic waveform from radial or brachial artery waveforms. One of the main challenges of this indirect method is related to the difficulty in recording and analyzing the brachial arterial pressure wave. Another important and yet unresolved problem is the current uncertainty about the reliability of the transfer functions applied either to radial or to brachial noninvasive arterial waveforms, especially when obtained under peculiar hemodynamic conditions, like those characterizing pregnancy, heart failure, and the elderly or young individuals. In the study by Protogerou et al.[1], central BP was assessed by means of an indirect method based on a generalized transfer function applied to the brachial pulse waves recorded through an oscillometric system. Although a validation study of this system has been published [26], in this validation study only central SBP values obtained from 30 patients were reported, and no data were provided on pulse waveform characteristics of the same individuals. Moreover, invasive validation studies concerning devices for assessing central BP, which only focus on central SBP values, carry the risk of providing misleading results, whenever they ignore the concomitant validation of the device ability to assess the arterial wall properties. In fact, given the significant and close linear correlation found by a number of studies between invasive central SBP, measured directly in the ascending aorta by a catheter, and brachial SBP, measured by an oscillometric method, one might come to the paradoxical suggestion that a relatively accurate measurement of aortic SBP might simply be obtained by subtracting 10 mmHg from brachial oscillometric SBP values, with no need of pulse waveform analysis [27]. Thus, given the importance of this topic, and because of the diverse approaches followed by the available validation studies, more rigorous criteria should urgently be provided by scientific international societies in order to establish reliable protocols and methods for a better standardized validation of devices aimed at assessing central BP. A major limitation of all systems currently proposed to estimate central BP is their inability to provide absolute values of aortic pressure. A calibration of the pulse waveform obtained through tonometric recordings is indeed always required, and two alternative calibration methods are usually followed, both of which have been evaluated in the study by Protogerou et al.[1]. According to the first approach, brachial SBP and DBP values determined by a validated conventional sphygmomanometric method are assigned to the peak and trough points of the tonometric pressure wave recorded at the level of the reference artery (i.e. brachial artery in the study by Protogerou et al.[1]). With the second approach, the brachial pulse waveform is calibrated using mean BP and DBP values again obtained by a validated conventional sphygmomanometric method. The latter calibration procedure is based on the observation that mean BP is constant throughout the large artery tree and that DBP does not change substantially from the central to the peripheral part of the arterial system [28,29]. In the study by Protogerou et al.[1], the correlation of central BP with cardiac damage was markedly different when different calibration methods were used. When mean and diastolic brachial BP values were applied for the calibration of the peripheral pressure waveform, 24-h average aortic SBP was significantly better associated with left ventricular mass than 24-h average brachial SBP. On the contrary, the correlation of 24-h aortic SBP with left ventricular mass was worse than that of 24-h brachial SBP when systolic and diastolic brachial BP values were used for calibration. Remarkably, however, SBP values were higher in aorta than in brachial artery when pulse waves were calibrated using mean and diastolic brachial BP. This counterintuitive finding contrasts with the widely held physiologic assumption that SBP actually increases ongoing from the aorta to peripheral arteries. The authors justify this result with a possible underestimation of the brachial SBP by the oscillometric method, suggesting that systolic and diastolic (rather than mean and diastolic) oscillometric BP values should be applied in calibration of peripheral pulse waveforms when assessing the amplification phenomenon. This suggestion appears, however, to be inconsistent with the demonstration provided by the authors themselves of a greater predicting value of central BP when calibrated based on the mean and diastolic brachial BP values, and weakens the clinical value of the correlation found in this study between the central pressure estimated in this way and cardiac damage. Several other studies showed that the two methods of calibration may lead to absolute differences in central SBP estimation of up to 15 mmHg between each other, and compared with invasive measurements, independently of the used device [26,30,31]. Also, imprecision in determining brachial mean pressure by oscillometry may negatively affect the accuracy of central BP estimation [31]. Understanding and addressing these discordances is, therefore, a crucial issue in the process of clinical implementation of central BP measuring devices. Despite the clear theoretical advantages of central 24-h BP monitoring, more investigations and technical improvements are thus needed before recommending central BP for routine clinical use, as wisely suggested by the 2013 ESH and ESC guidelines for the management of arterial hypertension [21]. Even more caution is needed when proposing ambulatory estimates of central BP all over the 24 h. Indeed, all available methods for estimating central BP have been tested and more or less properly validated at rest, with no systematic validation of their performance in ambulant individuals over 24 h. Such a dynamic validation, admittedly, is not an easy task and has to face a number of methodological difficulties. Similar difficulties are faced also when validating oscillometric devices for ABPM at the brachial artery level, a validation which is commonly done only at rest [32]. The accuracy at rest of ABPM devices is then somehow uncritically extrapolated to the dynamic conditions of a truly ambulatory recording. The only partial justification for this procedure is that individuals are advised to stop any activity and to keep their arm still at the time of each oscillometric cuff inflation [12]. In the past, only a few studies attempted to validate ABPM devices in truly dynamic conditions, and this was done against ambulatory intra-arterial BP recordings. These studies clearly showed that the discrepancy between automated BP readings and intra-arterial BP values was much greater in ambulatory conditions than at rest [33]. This approach can no longer be recommended nowadays, both for technical and ethical reasons. Research is, therefore, still needed to develop more suitable protocols to validate devices for ambulatory central or peripheral BPM. These protocols, for example, should allow the dynamic assessment of the accuracy of devices for central and peripheral ABPM against noninvasive reference standards in a laboratory environment by simulating some of the activities and recording conditions of daily life. In conclusion, the study by Protogerou et al.[1] provides interesting suggestions on the possible clinical relevance of central ABPM. However, a number of yet unresolved methodological issues related to the calibration and accuracy of central BP estimates, in particular when obtained under ambulatory conditions, still do not allow to recommend this approach in clinical practice and strongly suggest the need of additional studies in this stimulating field. ACKNOWLEDGEMENTS All authors had access to the data and a role in writing this article. Conflicts of interest P.S. is a consultant for DiaTecne s.r.l. The other authors have no conflicts to report.

Intra-arterial versus oscillometric blood pressure measurements in women with severe peripartum hypertension undergoing urgent treatment with nicardipine: An observational study.

WS-2. Dysregulation of autotaxin-lysophosphatidic acid signaling system in preeclamptic placenta

Intra-arterial blood pressure measurements recorded during the first week of life in 32 stable very low birth weight infants (20 of birth weight up to 1250 g and 12 with birth weight 1251-1500 g) were reviewed. None of the infants received inotropic drugs or were given infusions of colloids to manipulate the blood pressure during the periods from which the recordings were taken. The mean systolic, mean and diastolic blood pressure measurements for infants of birth weight greater than 1250 g were significantly higher than those recorded in the infants of birth weight of up to 1250 g (figure 1). The mean blood pressure (calculated by adding one third of the pulse pressure to the diastolic pressure) in the larger infants showed a significant increase with increasing postnatal age, but this increase was not apparent in the smaller infants (figure 2). Figure 3 shows the range of systolic, mean and diastolic blood pressure values that were recorded. The mean values were remarkably constant with diastolic blood pressure varying between 31 and 34 mmHg, mean blood pressure between 35 mmHg and 40 mmHg, and systolic blood pressure between 46 mmHg and 52 mmHg. Intra-arterial lines provide a convenient and accurate route for blood pressure monitoring. It is important that a normal range of blood pressure values in the very low birth weight infant is established so that hypotension, with the potential risk of cerebral ischemia, can be avoided.