Baseline Blood Pressure Changes Research Articles

Dietary magnesium intake is related to larger brain volumes and lower white matter lesions with notable sex differences

PurposeTo examine the association between dietary magnesium (Mg) intake and brain volumes and white matter lesions (WMLs) in middle to early old age.MethodsParticipants (aged 40–73 years) from UK Biobank (n = 6001) were included and stratified by sex. Dietary Mg was measured using an online computerised 24 h recall questionnaire to estimate daily Mg intake. Latent class analysis and hierarchical linear regression models were performed to investigate the association between baseline dietary Mg, Mg trajectories, and brain volumes and WMLs. Associations between baseline Mg, and baseline blood pressure (BP) measures, and baseline Mg, Mg trajectories and BP changes (between baseline and wave 2) were also investigated to assess whether BP mediates the link between Mg intake and brain health. All analyses controlled for health and socio-demographic covariates. Possible interactions between menopausal status and Mg trajectories in predicting brain volumes and WMLs were also investigated.ResultsOn average, higher baseline dietary Mg intake was associated with larger brain volumes (gray matter [GM]: 0.001% [SE = 0.0003]; left hippocampus [LHC]: 0.0013% [SE = 0.0006]; and right hippocampus [RHC]: 0.0023% [SE = 0.0006]) in both men and women. Latent class analysis of Mg intake revealed three classes: “high-decreasing” (men = 3.2%, women = 1.9%), “low-increasing” (men = 1.09%, women = 1.62%), and “stable normal” (men = 95.71%, women = 96.51%). In women, only the “high-decreasing” trajectory was significantly associated with larger brain volumes (GM: 1.17%, [SE = 0.58]; and RHC: 2.79% [SE = 1.11]) compared to the “normal-stable”, the “low-increasing” trajectory was associated with smaller brain volumes (GM: − 1.67%, [SE = 0.30]; white matter [WM]: − 0.85% [SE = 0.42]; LHC: − 2.43% [SE = 0.59]; and RHC: − 1.50% [SE = 0.57]) and larger WMLs (1.6% [SE = 0.53]). Associations between Mg and BP measures were mostly non-significant. Furthermore, the observed neuroprotective effect of higher dietary Mg intake in the “high-decreasing” trajectory appears to be greater in post-menopausal than pre-menopausal women.ConclusionsHigher dietary Mg intake is related to better brain health in the general population, and particularly in women.

Abstract P186: Specific Knockout of Sox6 in Renin Expressing Cells Cause a Decrease in Renin Expression and Changes to Vascular Reactivity

Introduction: Sox6 is a transcription factor known to be important for specification of different cell lineages, and important during embryonic development in vertebrates. Our group recently found that Sox6 plays a new function in renin expression control. Renin is an enzyme that controls the rate limiting step in the Renin Angiotensin Aldosterone System, a key regulator of blood pressure and thus hypertension. Here we report new findings in a novel transgenic mouse in which Sox6 is specifically knocked out in Renin expressing cells (Ren1d Cre /Sox6 fl/fl -Sox6 KO). Methods: Sox6 KO was used to determine the impact of Sox6 ablation in renin expressing cells on renin expression. Blood pressure and heart rate variability were measured by telemetry. Vascular reactivity was measured by wire myography and sympathetic nervous system renal input was determined by renal catecholamines assay. Results: We found that the specific Sox6 ablation in renin expressing cells produced a significant decrease in renin expression at a protein (40% fold decrease, n=7, P=0.01) and mRNA level (37 % fold decrease, n=4, P=0.01) compared to wild type mice. Our data indicates that Sox6 KO has no significant change in baseline blood pressure. However, there is a decrease in heart rate variability in Sox6 KO mice compared to wild type, indicating a dysregulation in the sympathetic and parasympathetic nervous systems (3.22±0.19 vs 1.14±0.32 LF/HF, n=10-13, P<0.05). Regarding vascular function, Sox6 KO mice have an enhanced sensitivity to vasodilators compared to wild type mice which may compensate for the decrease in renin expression (difference in response to sodium nitroprusside was found between 3 nM and 30 nM, n=3-11, P<0.05) and no difference in Acetylcholine response at any concentration. Furthermore, preliminary data indicates that there are no detectable differences in renal norepinephrine concentration between Sox6 KO and wild type mice. Conclusion: Our data indicate that Sox6 has a new function in renin-expressing cells that modulate blood pressure, heart rate variability, and vascular reactivity. Currently we are studying changes in the expression of vascular tone genes in endothelial and smooth muscle cells and changes in the sympathetic tone in the kidney and vascular system.

Heterogeneity of Clinical Trials for Antihypertensive Drugs in Japan: Exploratory Analysis of Confirmatory Phase III Trials Used for Marketing Approval.

The results of pivotal trials, which provide a rationale for marketing approval decisions for new drugs, are considered for various comparative purposes in postmarketing analyses. Using meta-regression analysis of 91 randomized controlled trials of 61 approved antihypertensive drugs in Japan, we show that mean baseline blood pressure (BP) of each arm was associated with predetermined entry criteria (EC), age, and trial start year (TSY). BP changes following treatment were associated with EC, subject characteristics (e.g., age, complications, baseline BP), study design (e.g., concomitant drug use), and TSY. Effect sizes were generally larger in trials for the first and second drugs in the same class than in trials for follow-on drugs. Results of pivotal trials may vary depending on many factors, suggesting possible challenges associated with the comparison of these results indirectly. Due to the heterogeneity in pivotal trials, caution should be exercised when comparing approved drugs and conducting meta-analyses retrospectively.

Blood Pressure Management and Evolution of Thrombolysis-associated Intracerebral Hemorrhage in Acute Ischemic Stroke

There is limited knowledge on the radiographic features of thrombolysis-induced hemorrhage. The factors that influence early hematoma expansion have not been elucidated. Patients presenting with a symptomatic intracerebral hemorrhage (ICH) as a result of intravenous (IV) thrombolysis with tissue plasminogen activator (tPA) for acute ischemic stroke and had noncontrast computed tomographic (CT) scans of the head were included in this retrospective study. Calculation of hematoma volumes was obtained. Analysis of covariance was used to evaluate for the effect of baseline blood pressure (BP) on initial hematoma volume and further growth. Of 267 patients who were treated with intravenous tPA for acute ischemic stroke at our facility between January 1, 2005 and December 31, 2009, 17 patients developed symptomatic ICH and were included in the final analysis. There was a positive correlation between baseline level of systolic BP after thrombolysis and initial hematoma volume (r = 0.46; P = .03) but not for the diastolic BP (r = 0.07; P = .40). There was a significant increase in mean hematoma volume expansion when comparing results between the first and second CT scans (median 9 hours, 22 minutes; 14.9 ± 19.6 cm(3) to 26.0 ± 26.7 cm(3); P = .04). There was also a negative association between the reduction of systolic BP and hematoma growth (r = -0.67; P = .02), but no correlation with change in diastolic BP (r = -0.22; P = .28). Once diagnosed, thrombolysis-induced symptomatic ICH undergoes significant early expansion in size. Systolic BP may play a role in hematoma expansion.

Predictors of First-Fill Adherence for Patients With Hypertension

Between the promise of evidence-based medicine and the reality of inadequate patient outcomes lies patient adherence. Studies of prescription adherence have been hampered by methodologic problems. Most rely on patient self-report of adherence or cross-sectional data of plan-wide prescription fills to estimate patient-level adherence. We conducted a retrospective cohort study and linked individual patient data for incident prescriptions for antihypertensive medications from electronic health records (EHRs) to claims data obtained from the patient's insurance plan. Clinical data were obtained from the Geisinger Clinic, a 41 site group practice serving central and northeastern Pennsylvania with an EHR in use since 2001. Adherence was defined as a prescription claim generated for the first-fill prescription within 30 days of the prescribing date. Of the 3,240 patients written a new, first-time prescription for an antihypertensive medication, 2,685 (83%) generated a corresponding claim within 30 days. Sex, age, therapeutic class, number of other medications prescribed within 10 days of the antihypertensive prescription, number of refills, co-pay, comorbidity score, baseline blood pressure (BP), and change in BP were significantly associated with first-fill rates (P < 0.05). Patients who are older, female, have multiple comorbidities, and/or have relatively lower BPs may be less likely to fill a first prescription for antihypertensive medications and may be potential candidates for interventions to improve adherence to first-fill prescriptions.

Treatment with enalapril modifies the pain perception pattern in hypertensive patients.

The cardiovascular system shares numerous anatomic and functional pathways with the antinociceptive network. The aim of this study was to investigate whether angiotensin-converting enzyme (ACE) inhibitor treatment could affect hypertension-related hypalgesia. Twenty-five untreated hypertensive patients, together with a control group of 14 normotensive subjects, underwent dental pain perception evaluation by means of a pulpar test (graded increase of test current applied to healthy teeth). After the evaluation of the dental pain threshold (occurrence of pulp sensation) and tolerance (time when the subjects asked for the test to be stopped), all the subjects underwent a 24-hour ambulatory blood pressure monitoring. The hypertensive group then was treated with 20 mg/d enalapril, whereas the normotensive subjects remained without any treatment. After a time interval of 6+/-2 months, the dental pain sensitivity was retested in all the subjects, and ambulatory blood pressure was recorded during treatment in the hypertensive patients. At the first assessment, hypertensive patients showed a higher pain threshold than normotensive subjects (P<.001). On retesting of pain sensitivity in hypertensive patients, a significant decrease of both pain threshold and tolerance, leading to their normalization, was observed during treatment (P<.001 and P<.005, respectively), in the presence of reduced 24-hour and office blood pressure values. A slight, though significant, correlation was observed between variations in pain tolerance and baseline blood pressure changes occurring during treatment. During follow-up, the normotensive subjects did not show any significant pain perception or office blood pressure changes. Hypertension-related hypalgesia was confirmed. Mechanisms acting both through lowering of blood pressure and specific pharmacodynamic properties may account for the normalization of pain sensitivity observed in hypertensive patients during treatment with ACE inhibitors.

Modulation of the cardiovascular defence response by low frequency stimulation of a deep somatic nerve in rats

In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation in the dorsal part of the periaqueductal grey matter (PAG) produced a pressor response with tachycardia and vasodilatation in the hind limb, a pattern known as the ‘cardiovascular defence reaction’ owing to its resemblance to fear-induced hemodynamic changes. Following a 20-min period of stimulation of the peroneal nerve at 10 Hz with current intensities sufficient to recruit group II and III fibres the pressor component of the response was significantly reduced compared to control rats. The maximum decrease of the PAG-evoked pressor response was about 50% (from 32.0 ± 0.7 to 16.6 ± 5.9 mmHg). The effect lasted for between 60 and 290 min and was not correlated to baseline blood pressure changes observed after the stimulation of the nerve. In contrast, the tachycardia and hind limb vasodilator components of the defence response as well as their baseline values remained unchanged. Resting bloodpressure did not change significantly in control rats but showed a small progressive increase in stimulated rats which reached significance 90–100 min after the stimulation. These results suggest that the afferent input from hgih threshold fibres in a muscle nerve can produce a selective and long-lasting depression of the vasoconstrictor components of the midbrain-evoked cardiovascular defence response. This effect is discussed in relation to the long-lasting sympathoinhibitory effects of acupuncture-like stimulation or sustained physical exercise.

Psychological, physiological and physical characteristics of subjects at risk for essential hypertension

This study compared characteristics of subjects who had a parental history of hypertension (FH + group, n = 51) with those who did not (FH - group, n = 49). Subjects took personality questionnaires and self-ratings of alcohol use. State effects were measured just before the experiment. Baseline blood pressure (BP) and BP changes in response to a mental arithmetic stress task were recorded. Personality and state affect measures were factor analyzed yielding five factors: state dysphoria (Dys) vs positive affect (PA); sensation seeking (SS)-psychoticism (P); trait anger-anger-out; extraversion (E)-Type A; neuroticism (N)-anger-in. A stepwise discriminant function analysis was used to discriminate female and male FH + and FH - groups. Results indicated that men seem to inherit a specific BP overreactivity to stress compounded with a tendency toward overweight while the genetic link in women may be mediated by more general emotional states and traits.

Do Centrally-Acting Antihypertensive Drugs Act at Non-Adrenergic as well as Alpha-2 Adrenoceptor Sites?

Rabbits were treated with guanabenz, clonidine and rilmenidine for 6 days via osmotic minipumps. Blood pressure, heart rate and responses to intracisternal clonidine were measured after 1 and 6 days treatment. Radioligand binding to forebrain and hindbrain membranes after 6 days treatment was examined using [3H]yohimbine to measure the number of adrenergic binding sites and [3H]clonidine and [3H]idazoxan to assess nonadrenergic imidazoline sites. No change in nonadrenergic imidazoline binding was observed but adrenergic binding was decreased in forebrain and hindbrain by guanabenz and in hindbrain by clonidine treatment. Resting heart rate was decreased after 1 day's treatment with partial recovery by day 6. At this time heart rate significantly reduced in the clonidine and rilmenidine treated groups but not the guanabenz group. No significant change in baseline blood pressure was observed in normotensive rabbits. Both depressor and bradycardia responses to intracisternal clonidine were attenuated after 1 day's dosing but only depressor responses were influenced after 6 days. Blood pressure and heart rate thus appeared to be regulated independently. It is possible that imidazoline receptors predominate in the central control of blood pressure while central alpha-2 adrenoceptors play a greater part in heart rate regulation.

Adrenal demedullation and peripheral 6-OHDA administration in the rabbit: Effects on body weight, general activity and cardiovascular responsivity

Two experiments were undertaken to determine the effects of systemic 6-hydroxydopamine (6-OHDA) administration and adrenal enucleation on body weight, brain and heart norepinephrine, general activity, and cardiovascular responsivity in the rabbit. 6-Hydroxydopamine produced long lasting, dose related decreases in baseline blood pressure (BP) and in pressor responses following electric shock. Partial reversal of the BP changes was observed in nonenucleated animals tested 20 days after 6-OHDA administration but not in enucleated animals tested 5, 10 or 20 days post-injection or in control animals tested 5, 10 or 15 days after vehicle injection. Although 6-OHDA administration produced transient weight loss and activity decrements, no long term weight or activity changes were observed.

Interactions between sino-aortic reflexes and cardiovascular effects of sleep and emotional behavior in the cat.

The role of sino-aortic reflexes in the control of circulation during normal behavior was investigated by comparing cardiovascular reactions during various but reproducible types of behavior before and after bilateral sino-aortic deafferentation. Chronic deafferentation caused little change in baseline blood pressure, but a subtler, important role of sino-aortic reflexes was revealed by examining the integrated cardiovascular responses to behavioral stimuli. During desynchronized sleep, the buffering action of sino-aortic reflexes prevented a marked and diffuse vasodilation, with an action that was particularly evident on muscle blood vessels. During emotional behavior, especially when emotion was accompanied by movement, sino-aortic reflexes opposed the consequences of muscle vasodilation by inducing tachycardia and vasoconstriction in the viscera and in noncontracting muscles. A reciprocal type of interaction between behavior and sino-aortic reflexes was shown by testing the amplitude of the carotid occlusion response before and during desynchronized sleep; the latter condition was consistently associated with decreased effectiveness of the reflex response. The possibility is considered that this might indicate central suppression of the carotid sinus reflex during desynchronized sleep and that a similar inhibitory interference might occur during emotional behavior. Alternatively, reduction of the reflex response might result from a shift of the stimulus-response curve on either side of its steep portion.