The March issue of the Journal of Hypertension starts with a consensus paper of the Working Group on Obesity and Diabetes of the European Society of Hypertension on the protective effects of new blood glucose lowering agents (Kotsis et al., pp. 377–386). The article reviews the evidence that in type 2 diabetes sodium-glucose co-transporter 2 (SGLT-2) inhibitors as well as glucagon-like peptide 1 (GLP-1) receptor agonists can not only effectively lower blood glucose but also favour weight loss, reduce blood pressure (BP), and improve nonalcoholic fatty liver disease, an array of beneficial effects, which explains why these drugs have been shown to reduce cardiovascular morbidity and mortality in randomized outcome trials. This has been a major achievement of recent cardiovascular research, which has expanded to macrovascular protection the protective effects of glucose-lowering treatment previously unequivocally demonstrated only for diabetes-related microvascular disease. Sundström et al. (pp. 387–394) show the results of an analysis of a large cohort of men and women in which weight gain at a young age (20 years) exhibited a relationship with mid-life blood pressure (BP) values, a 10 kg weight increase being accompanied by more than 2 or 3 mmHg increase of SBP. In the words of the authors, ‘The magnitude of this association indicates a potentially great impact of strategies that prevent weight gain on public health’. Stergiou et al. (pp. 395–399) report on an initiative for improving blood pressure measurements, which will be coordinated by a group of worldwide known experts supported by major scientific societies on hypertension. This follows other initiatives for a better standardization and accuracy of BP measurement in clinical practice, one of which was published in Journal of Hypertension not so long ago. Attempts to make the BP values measured in the doctor's office more precise and to achieve a better standardization across the world are strongly justified, because non-marginal errors are common, with serious consequences for the decision on whether drug treatment is needed and control by treatment has been achieved.
Four articles of the current issue of the Journal address epidemiological aspects of hypertension. Casiglia et al. (pp. 412–419) describe the results of a large (>23 000 participants) multicentre cohort study (URRAH) on the association of serum uric acid with the risk of coronary disease. Confirming previous evidence elevated uric acid levels were accompanied by an increased risk of myocardial infarction. The most interesting observation, however, was that the serum uric acid level at which the risk of myocardial infarction showed a noticeable increase was less than 5.70 mg/dl in men and less than 5.20 mg/dl in women, that is, cutoffs much lower than those previously considered as reflecting a condition of cardiovascular alarm, which have been for years close to the level at which gout becomes manifest. Monzo et al. (pp. 420–425) show that visit-to-visit BP variability was associated with cardiovascular morbidity and hospitalization in the 2549 patients with heart failure and reduced left ventricular ejection fraction recruited for the EMPHASIS-HF trial. This is a new interesting finding, both because of the large number of patients studied and because of the measurement of BP variability as the coefficient of variation of the mean BP value, whose confounding influence on the results was thus excluded. Additional interesting points made by the article are that the results were not modified by treatment with the drug of interest (eplerenone) as well as that at low and high mean BP values visit-to-visit BP variability exhibited an opposite association with outcomes, that is, lower variabilities were accompanied by increased outcomes and vice-versa. This is in line with recent observations suggesting that the origin and clinical significance of visit-to-visit BP variability is not clear. Namely, that under certain circumstances visit-to-visit BP variability might be a marker, not a cause of a compromised clinical situation (reverse causality). Liu et al. (pp. 426–433) show that in a large number of patients with a variety of newly diagnosed cancers (n = 22 500), cardiovascular diseases represented the top comorbidities, hypertension being the most common one. Salazar et al. (pp. 434–440) show that in chronic kidney disease, masked hypertension is commonly (one-third of the patients) associated with isolated nocturnal hypertension, which may thus represent the most frequent phenotype of this condition. As nocturnal BP is more strongly associated with cardiovascular events than diurnal BP, this may explain why in masked hypertension cardiovascular risk is high. Further considerations on this phenomenon can be found in the Editorial Commentary of Mulè and Cottone (pp. 400–402).
The next seven studies address diagnostic aspects of hypertension (two articles) and the complex relationship between BP abnormalities and cardiac or vascular damage. As far as the diagnostic aspects are concerned, Savvari et al. (pp. 441–447) show that in more than 2400 patients aged 50 years or more, ambulatory BP monitoring allowed to detect a relatively high number of patients with atrial fibrillation (12.5%), the prevalence of this condition being almost twice as large in patients aged at least 75 years. Interestingly, no greater prevalence of atrial fibrillation was seen in white coat or masked hypertension. Lyu et al. (pp. 448–455) find that poor sleep quality, as assessed by polysomnography, was associated with nondipping both cross-sectionally and longitudinally, over a follow-up of more than 7 years. This is an often forgotten association which leads physicians to label patients as nondippers based on a single ambulatory BP monitoring, with no concern for the possibility that just an occasional night of poor sleep may be responsible. It has long been shown that the dipping/nondipping status is poorly reproducible as exemplified, many years ago, by the observation that in the SAMPLE study 40% of non-dippers or dippers at the first monitoring changed status at the second monitoring. The above limitation, the factors responsible for an attenuation of nocturnal hypotension and the means by which a normal nocturnal hypotension may be restored by treatment are addressed in the Editorial Commentary of Pengo et al. (pp. 403–404).
Concerning organ damage, Anam Mir et al. (pp. 456–466) provide data on the involvement of chromogranin A (CHGA) on kidney injury via mesangial cells and gene expression of inflammation in a chronic kidney disease mouse model. Einarsen et al. (pp. 467–473) report a high prevalence (20%) of left ventricular diastolic dysfunction in middle-aged survivors of an ischemic stroke. Petersson Rosberg and Nilsson (pp. 474–480) show that central pulse wave velocity of offsprings, parents and grandparents exhibits a positive correlation. Although a shared environment may contribute, this speaks in favour of a genetic determinant of arterial stiffness. Nilsson and Sperling (pp. 481–488) describe a positive association between central pulse wave velocity in adults and body weight at birth, which suggests that factors involved in the determination of large artery mechanical properties start operating very early in life. Finally, Joles et al. (pp. 489–503) show that in patients with chronic kidney disease, left ventricular hypertrophy exhibited a regression when, after 6 months from kidney transplantation, BP was normalized from the previously elevated values and renal function was restored. Left ventricular fibrosis persisted, however, which may mean that under these conditions, regression of left ventricular hypertrophy does not achieve complete tissue normalization or that achieving this goal needs a longer time.
The final six articles deal with antihypertensive drug treatment. Brandt et al. (pp. 504–510) report that in the Heinz Nixdorf Recall Study, the percentage of treated hypertensive patients increased substantially from a 2000--2003 to a 2005–2008 survey (60.3% vs. 75.1%, respectively). This was not accompanied, however, by an increased rate of BP control, which may indicate that a persistently poor adherence to the prescribed antihypertensive drug regimen is responsible. Therapeutic inertia may also be involved, however, because the medicine-dosing rate was not substantially different between patients achieving or not achieving BP control. Venäläinen et al. (pp. 511–518) report that in the patients of the SPRINT trial, a subset of baseline variables successfully predicted both cardiovascular outcomes and acute renal injury during the on-treatment years of the trial. According to the authors, this might allow to predetermine which patients might benefit and which not from the aggressive BP reduction used in the trial. Ho et al. (pp. 519–526) report that in a post-hoc analysis of the ALLHAT database, there was little or no difference in the short or long (14 years) risk of cardiovascular outcomes in patients who at recruitment were under antihypertensive drugs versus those who were treatment ‘naïve’. This implies that delaying BP-lowering treatment may not have adverse consequences, which is against the notion, however, that the ‘early the treatment the better’ is for the patient.
Shin et al. (pp. 527–535) show that in a large number of Korean hypertensive patients, the vasodilating beta-blocker nebivolol effectively reduced BP in a variety of different therapeutic settings, that is, when given to newly treated individuals, when added to previous antihypertensive drugs, when replacing existing treatment and so on. Del Mauro et al. (pp. 536–545) show that in spontaneously hypertensive rats, amlodipine, nebivolol, and another vasodilator beta-blocker (carvedilol), all effectively lowered BP and BP variability. Most importantly, they prevented cardiac hypertrophy as well as cardiac and aortic collagen deposition more effectively than atenolol, adding to the available evidence that a concomitant vasodilatation may increase the protective effects of beta-blockers against organ damage. This is discussed in the Editorial Commentary of Del Pinto et al. (pp. 405–407). Spannella et al. (pp. 546–552) show that in hypertensive patients under statin therapy, ambulatory SBP was slightly lower (about 3 mmHg) than in control patients, after adjustment for confounding factors and use of propensity score matching. The BP-lowering effect of statins has been under discussion for many years with variable results. Statins have the potential for lowering BP because they reduce arterial stiffness, which is a determinant of SBP values. BP reduction has never been conclusively established, however, and data from prospective randomized trials have usually been largely negative. In the PHYLLIS trial, for example, addition of pravastatin to antihypertensive treatment did not lower day and night BP over a three-year follow-up during which ambulatory BP was measured at yearly intervals. The issue is discussed by the Editorial Commentary of Thomopoulos et al. (pp. 408–411).
The very final article published in the March issue is a case report of a patient with a history of long-term extended radiotherapy of the neck because of a carcinoma of the right palatal tonsil. High BP values, BP variability and postural syncope made carotid baroreflex failure the likely diagnosis, a confirmation of which came from the results of autonomic nervous system functional tests. Neck irradiation should be regarded as a possible cause of baroreflex failure and patients’ follow-up adjusted accordingly.
Conflicts of interest
There are no conflicts of interest.