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Biomedical subjects

R Fagard

Publications and source records attributed to R Fagard.

At least 91 records · Page 5Linked to original sources
PubMed1997

Comparison of maximum versus submaximum exercise testing in providing prognostic information after acute myocardial infarction and/or coronary artery bypass grafting.

Exercise testing after acute myocardial infarction (AMI) provides prognostic information. In many studies submaximum exercise tests performed until a given work load, metabolic equivalents (METs) level, or heart rate were used or patients discontinued the exercise test prematurely because of symptoms. We showed recently that peak oxygen uptake during maximum exercise provides independent prognostic information in patients with coronary artery disease. It is, however, not known whether maximum exercise testing is superior in predicting mortality than testing until a target level. Second, it is unclear which target end point best classifies patients at increased risk. Therefore, the independent relation between mortality and indexes of, respectively, maximum and submaximum exercise capacity, were analyzed in 527 patients, who were tested until exhaustion. To express submaximum exercise capacity dichotomous variables (the ability to reach a target METs level or not), and a continuous variable relative to maximum exercise capacity (the ventilatory anaerobic threshold) were used. After adjustment for significant covariates, peak oxygen uptake was significantly related to all-cause and cardiovascular mortality. The target level of 5 METs and the ventilatory anaerobic threshold, when expressed in absolute workload, were related to mortality when unadjusted, but after adjustment for age and other confounders significancy was lost. In multiple Cox regression analysis, the prognostic power of peak oxygen uptake remained significant when 5 METs or the anaerobic threshold were forced into the equations. When analyzing the relation of various METs levels with mortality, the 7 METs level was independently related to all-cause and cardiovascular mortality and yielded the highest diagnostic accuracy. We conclude that maximum exercise testing is more potent in predicting mortality than the ability to reach a predetermined level of exercise, such as the commonly used 5 METs level or the anaerobic threshold. Otherwise, the use of a higher target level of 7 METs is recommended.

Adult↗
PubMed1997

Effect of antihypertensive drug treatment on cardiovascular outcomes in women and men. A meta-analysis of individual patient data from randomized, controlled trials. The INDANA Investigators.

BACKGROUND: Trials of drug therapy for hypertension have shown that such therapy has a clear overall benefit in preventing cardiovascular disease. Although these trials have included slightly more women than men, it is still not clear whether treatment benefit is similar for both sexes. OBJECTIVE: To quantify the average treatment effect in both sexes and to determine whether available data show significant differences in treatment effect between women and men. DESIGN: Subgroup meta-analysis of individual patient data according to sex. Analysis was based on seven trials from the INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) database and was adjusted for possible confounders. PATIENTS: 20,802 women and 19,975 men recruited between 1972 and 1990. INTERVENTIONS: Primarily beta-blockers and thiazide diuretics. RESULTS: In women, treatment effect was statistically significant for stroke (fatal strokes and all strokes) and for major cardiovascular events. In men, it was statistically significant for all categories of events (total and specific mortality, all coronary events, all strokes, and major cardiovascular events). The odds ratios for any category of event did not differ significantly between men and women. In absolute terms, the benefit in women was seen primarily for strokes; in men, treatment prevented as many coronary events as strokes. Graphical analyses suggest that these results could be completely explained by the difference in untreated risk. CONCLUSIONS: In terms of relative risk, treatment benefit did not differ between women and men. The absolute risk reduction attributable to treatment seemed to depend on untreated risk. These findings underline the need to predict accurately the untreated cardiovascular risk of an individual person in order to rationalize and individualize antihypertensive treatment.

Adrenergic beta-Antagonists↗
PubMed1997

Therapy in old patients with isolated systolic hypertension: fourth progress report on the Syst-Eur trial.

The Syst-Eur trial is a multicentre, randomized, double-blind, placebo controlled therapeutical trial in patients at least 60 years old and with isolated systolic hypertension. Its scope is to investigate the effects of modern antihypertensive drug treatment on morbidity and mortality and to assess possible adverse effects of the drugs used. Patients were recruited in 22 countries in western and eastern Europe and Israel. At three run-in visits 1 month apart their sitting systolic blood pressure (SBP) on single-blind placebo treatment averaged 180-219 mm Hg with diastolic blood pressure (DBP) lower than 95 mm Hg. After stratification for sex and the presence of cardiovascular complications, the patients were randomized either to active treatment or placebo. Active treatment consisted of nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day) and/or hydrochlorothiazide (12.5-25 mg/day), titrated or combined to reduce the sitting SBP by at least 20 mm Hg to below 150 mm Hg. Matching placebos were employed similarly. The present progress report is based on the data received at the Coordinating Office before 1 March 1996. At that time 3433 subjects had been randomized. A total of 2015 patients had been followed for at least 1 year on double-blind treatment and 1298 patients for at least 2 years. At baseline BP was similar in both treatment groups and averaged 174/86 mm Hg. According to a per-protocol analysis at 1 year, BP fell (P < 0.001) on average by 22.6 +/- 15.7/6.0 +/- 8.0 mm Hg in the active treatment group and by 12.2 +/- 15.9/1.7 +/- 7.3 mm Hg in the placebo group. At 2 years BP was 10.2/5.7 mm Hg lower (P < 0.001) on active treatment than on placebo. At 1 year the percentage of patients who had reached goal BP was 19.9% in the placebo group and 41.4% in the active treatment group. At 2 years these percentages were 20.9 and 43.2 respectively.

Aged↗
PubMed1997

Conventional and ambulatory blood pressure and menopause in a prospective population study.

Whether menopause would be associated with a rise in blood pressure (BP) was prospectively assessed in a cohort study. A total of 315 women (30-70 years at follow-up) were randomly selected from the population. They were matched on age and rank of body mass index with 315 men. Five BP readings were obtained by conventional sphygmomanometry (CBP) at the subjects' homes on each of two baseline visits and at one follow-up visit. The 24-h ambulatory BP was recorded at follow-up. Menstrual status was assessed by questionnaire. The statistical tests were two-sided and accounted for age, body mass index, antihypertensive treatment, contraceptive pill intake or changes in these variables. From baseline to follow-up (median, 5.2 years), 166 and 105 women stayed pre- or postmenopausal, while menses ceased in 44 perimenopausal women. In cross-sectional analyses, the postmenopausal women, compared with their pre- and perimenopausal counterparts, had a 4-5 mm Hg higher systolic CBP (15 readings per subject) and 24-h BP (P < or = 0.05 for differences between peri- and postmenopausal women). Furthermore, systolic CBP rose nearly 5 mm Hg per decade more (P < or = 0.05) in peri- and postmenopausal women than in premenopausal subjects. In addition, the longitudinal results showed that systolic CBP did not change in women who stayed premenopausal throughout follow-up (P=0.71), but increased by approximately 4 mm Hg over 5 years in peri- (P=0.07) and postmenopausal (P= 0.01) subjects (P=0.02 for difference between pre-and postmenopausal women). Such trends were not observed for diastolic BP in women or for systolic and diastolic BP in men. In conclusion, menopause per se may potentiate the age-related increase in systolic pressure. Because confined to systolic pressure, this specific effect of menopause may be mediated via a reduction in arterial compliance.

Adult↗
PubMed1997

For how many days should blood pressure be measured at home in older patients before steady levels are obtained?

This study investigated the period of time that blood pressure (BP) should be measured at home in older patients in order to obtain steady BP values. Thirty-six men and 38 women (> or =60 years) were recruited at one family practice. At one office visit the family physician measured supine, sitting and standing BPs three times consecutively in each position. During 10 consecutive days, BP was measured at home five times daily. The supine and standing BPs were measured once in the morning and in the evening and the sitting BP once at noon. These home BP values were averaged over the first day (1-day), over the first 3 days (3-day) and all 10 days (10-day) of measurements. In both the supine (-5.1 mm Hg) and sitting (-3.8 mm Hg) positions the 10-day average systolic home BP was significantly lower than the corresponding office BP. The opposite was observed for the 10-day average standing home BP values (+7.3/+3.4 mm Hg). Comparison of the 3-day and 10-day average home BP values showed only a significantly lower 10-day than 3-day systolic BP level in the supine position (-1.1 mm Hg, 95% CI -1.9 to -0.2 mm Hg). Repeated measures ANOVA, showed a small but significant decrease over time only for the supine systolic home BP (-0.29 mm Hg per day, 95% CI -0.49 to -0.08 mm Hg per day). We conclude that in older subjects, 3 days of home measurements may suffice to obtain steady values for the sitting and standing BPs. A longer interval might be required for the supine BP.

Aged↗
PubMed1997

Salt and blood pressure in community-based intervention trials.

This article reviews community-based salt intervention trials. In the Belgian Salt Intervention Trial, a controlled 5-y intervention in two Belgian towns resulted in a reduction in urinary sodium of 17 mmol/24 h (P < 0.001) in adult (aged > or = 20 y) women in the intervention town, which differed from the concurrent trend (an increase of 8 mmol/24 h) in the control town (P = 0.01). However, both systolic (-7.5 compared with -7.9 mm Hg) and diastolic (-2.3 compared with -3.0 mm Hg) pressures declined to the same extent in women of the two towns. In adult men in the intervention town, decreases were observed in urinary sodium (-12 mmol/24 h) and in systolic (-5.6 mm Hg) and diastolic (-2.4 mm Hg) blood pressures, but these trends were the same in the control town (-12 mmol/24 h, -4.9 mm Hg, and 0.2 mm Hg, respectively). The Belgian study and the four other community-based salt intervention trials reviewed show that, in general, salt intake in the long-run cannot be restricted below 5 g/24 h. More moderate salt restriction may constitute a more realistic goal, but its influence on blood pressure in the community at large is probably trivial.

Adolescent↗
PubMed1997

Cytosolic calcium changes induced by angiotensin II in human peripheral blood mononuclear cells are mediated via angiotensin II subtype 1 receptors.

OBJECTIVE: To determine the effects of angiotensin II (AII) (1-8) on cytosolic free calcium concentrations in the absence and in the presence of the selective angiotensin subtype 1 (AT1) receptor antagonist losartan and of the selective angiotensin subtype 2-receptor antagonist P-186 in human peripheral blood mononuclear cells (PBMC). We also assessed the effect of the AII analogues AII (2-8), AII (3-8) and AII (4-8) on the cytosolic free-calcium concentration in human PBMC. METHODS: The cytosolic free-calcium concentration was assayed in human peripheral blood mononuclear cells by measuring the fluorescence of fura-2 entrapped by these cells. RESULTS: Administration of AII caused a concentration-dependent increase in the cytosolic free-calcium concentration in human peripheral blood mononuclear cells with a half-maximal increase at 5 x 10(-8) mol/l. Also administration of the heptapeptide AII (2-8) increased the intracellular free-calcium concentration in human PBMC, whereas AII (3-8) and AII (4-8) had no effect. The AII (1-8)-induced rise in cytosolic free-calcium concentration was blocked completely by losartan but not by P-186. CONCLUSION: Our data demonstrate that the effects of AII on the cytosolic free-calcium concentration in human PBMC are AT1 receptor-mediated since they were abolished by the specific AII AT1 receptor antagonist losartan but not by the specific angiotensin subtype 2 receptor antagonist P-186.

Angiotensin II↗
PubMed1997

The deletion/insertion polymorphism of the angiotensin converting enzyme gene and cardiovascular-renal risk.

OBJECTIVE: This meta-analysis attempted to derive pooled estimates for the associations between various cardiovascular-renal disorders and the deletion/insertion (D/I) polymorphism of the angiotensin converting enzyme (ACE) gene. METHODS: Case-control studies were combined, using the Mantel-Haenszel approach. Joint P values for continuous variables were calculated by Stouffer's method. Continuous measurements reported in different units were expressed on a percentage scale using the within-study mean of the II genotype as the denominator. RESULTS: The computerized database used for this analysis included 145 reports with an overall sample size of 49 959 subjects. Overall, possession of the D allele was associated with an increased risk of atherosclerotic and renal microvascular complications. In comparison with the II reference group, the excess risk in DD homozygotes (P < 0.001) was 32% for coronary heart disease (CHD; 30 studies), 45% for myocardial infarction (20 studies), 94% for stroke (five studies) and 56% for diabetic nephropathy (11 studies). The corresponding risk in DI heterozygotes amounted to 11% (P= 0.02), 13% (P= 0.02), 22% (P= 0.10) and 40% (P < 0.001), respectively. Hypertension (23 studies), left ventricular hypertrophy (five studies), hypertrophic or dilated cardiomyopathy (eight studies) and diabetic retinopathy (two studies) were not related to the DI polymorphism. Publication bias was observed for CHD, myocardial infarction and microvascular nephropathy, but not hypertension. In studies with DNA amplification in the presence of insertion-specific primers, the risk associated with the DD genotype increased to 150% [95% confidence interval (CI) 76-256; four studies] for diabetic nephropathy, but decreased to 12% (95% CI -3 to 28; seven studies) for CHD and 14% (95% CI -6 to 37; four studies) for myocardial infarction. On the other hand, the pooled odds ratios did not materially change if the meta-analysis was limited to articles published in journals with an impact factor of at least 4. Furthermore, compared with the II control group, the circulating ACE levels (29 studies) were raised 58 and 31% (P < 0.001) in DD and DI subjects, respectively. In contrast, plasma renin (10 studies), systolic and diastolic blood pressure (46 studies) and body mass index (30 studies) were not associated with the D allele. CONCLUSION: The D allele is not associated with hypertension, but behaves as a marker of atherosclerotic cardiovascular complications and diabetic nephropathy. These associations do not necessarily imply a causal relationship and may have been inflated by publication bias. Nevertheless, their possible therapeutic implications may be subject to further investigation in prospective (intervention) studies.

Alleles↗
PubMed1997

Nocturnal blood pressure fall on ambulatory monitoring in a large international database. The "Ad Hoc' Working Group.

A wide range of definitions is used to distinguish subjects in whom blood pressure (BP) falls at night (dippers) from their counterparts (nondippers). In an attempt to standardize the definition of nondipping, we determined the nocturnal BP fall and night-day BP ratio by 24-hour ambulatory monitoring in 4765 normotensive and 2555 hypertensive subjects from 10 to 99 years old. In all subjects combined, the systolic/diastolic nocturnal fall and corresponding ratio averaged (+/- SD) -16.7 +/- 11.0/ -13.6 +/- 8.1 mm Hg and 87.2 +/- 8.0%/83.1 +/- 9.6%, respectively. In normotensive subjects, the 95th percentiles were -0.3/-1.1 mm Hg for the nocturnal fall and 99.7%/98.3% for the night-day ratio. Both the fall and ratio showed a curvilinear correlation with age. The smallest fall and largest ratio were observed in older (> or = 70 years) subjects. A higher BP on conventional sphygmomanometry was associated with a larger systolic (partial r = .11) and diastolic (r = .12) nocturnal BP fall. The diastolic (r = .08) but not the systolic night-day ratio increased with higher conventional BP. The nocturnal BP fall was larger and the corresponding night-day ratio smaller in oscillometric (n = 5884) than in auscultatory (n = 1436) recordings, in males (n = 3730) than in females (n = 3590), and in Europe (n = 4556) than in the other continents (n = 2764). The distributions of the nocturnal BP fall and night-day ratio showed considerable overlap among normotensive and hypertensive subjects, but the overlap tended to be larger for the ratio than for the fall. Of all subjects, 3.2% had systolic and diastolic ratios of 100% or more. With adjustments applied for confounders, the probability of being a nondipper increased 2.8 times (95% confidence interval, 2.0-4.0) from 30 to 60 years and 5.7 times (4.4-7.4) from 60 to 80 years. The odds ratios were 1.0 (0.8-1.4) for males versus females. 1.6 (1.2-2.1) for subjects with definite hypertension versus normotensive subjects, 2.4 (1.2-4.7) for Asians (n = 2213, 96% Japanese) versus inhabitants of the other continents, and 2.4 (1.5-3.8) for subjects examined with auscultatory versus oscillometric devices. In conclusion, the mathematical definition of nondipping, ie, having a night-day ratio of 100% or more for systolic and diastolic BPs, closely approximated the 95th percentiles of the night-day ratio in normotensive subjects. The ratio depends less on BP level than the nocturnal BP fall and is therefore to be preferred in the definition of dipping status. Notwithstanding the present findings, the reproducibility of nondipping and its prognostic significance need further clarification.

Adolescent↗
PubMed1997

Determining the trough-to-peak ratio in parallel-group trials. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.

We explored how in parallel-group trials interindividual variability, correction for placebo effects, and smoothing of blood pressure profiles can be handled in measuring the trough-to-peak ratio in 244 individuals with isolated systolic hypertension (> or = 60 years) enrolled in the placebo-controlled Systolic Hypertension in europe Trial. Net treatment effects were computed by subtracting the mean changes from baseline during placebo (n = 133) from those during active treatment (n = 111). At entry, systolic/diastolic pressures averaged 176/86 mm Hg in the clinic and 149/80 mm Hg on 24-hour ambulatory monitoring. With corrections applied for baseline and placebo, nitrendipine (10 to 40 mg/d), with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d), reduced (P < .001) these blood pressure values by 16.6/7.3 and 9.8/4.7 mm Hg, respectively. The net trough-to-peak ratios were first determined from blood pressure profiles (12 hours) with 1-hour precision, synchronized by the morning and evening doses of the double-blind medication. According to the usual approach, disregarding interindividual variability, the systolic/diastolic net trough-to-peak ratios were 0.46/0.40 in the morning and 0.77/0.99 in the evening. In individual subjects, the baseline-adjusted trough-to-peak ratios were nonnormally distributed. We therefore used a nonparametric technique to calculate the net trough-to-peak ratios from the results in individual subjects. In the morning, these ratios averaged 0.25 systolic (95% confidence interval, 0.09 to 0.41) and 0.15 diastolic (95% confidence interval, 0.00 to 0.31) and in the evening, 0.19 and 0.36 (95% confidence intervals, 0.00 to 0.38 and 0.14 to 0.56), respectively. When the blood pressure profiles were smoothed by substituting the 1-hour averages by moving or fixed 2-hour averages or by Fourier modeling, the trough-to-peak ratios remained unchanged after the morning dose (0.20/0.13, 0.20/0.14, and 0.16/0.21, respectively) but tended to increase in the evening (0.32/0.38, 0.28/0.40, and 0.48/0.49). In conclusion, the parallel-group analysis proposed makes it possible for one to correct the trough-to-peak ratio for baseline as well as placebo, to account for interindividual variability, and to calculate a confidence interval for the net trough-to-peak ratio. Accounting for interindividual variability reduces the trough-to-peak ratio. Smoothing affects the individualized net trough-to-peak ratios in an unpredictable way and should therefore be avoided.

Aged↗
PubMed1997

Effect of antihypertensive treatment in patients having already suffered from stroke. Gathering the evidence. The INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) Project Collaborators.

BACKGROUND AND PURPOSE: Drug treatment of high blood pressure has been shown to reduce the associated cardiovascular risk. Stroke represents the type of event more strongly linked with high blood pressure, responsible for a high rate of death or invalidity, and with the highest proportion of events that can be avoided by treatment. Hypertensive patients with a history of cerebrovascular accident are at particularly high risk of recurrence. Specific trials of blood pressure lowering drugs in stroke survivors showed inconclusive results in the past. METHODS: We performed a meta-analysis using all available randomized controlled clinical trials assessing the effect of blood pressure lowering drugs on clinical outcomes (recurrence of stroke, coronary events, cause-specific, and overall mortality) in patients with prior stroke or transient ischemic attack. RESULTS: We identified 9 trials, including a total of 6752 patients: 2 trials included 551 hypertensive stroke survivors; 6 trials of hypertensive patients included a small proportion of stroke survivors (536 patients); 1 trial included stroke survivors, whether hypertensive or not (5665 patients). The recurrence of stroke, fatal and nonfatal, was significantly reduced in active groups compared with control groups consistently across the different sources of data (relative risk of 0.72, 95% confidence interval: 0.61 to 0.85). There was no evidence that this intervention induced serious adverse effect. CONCLUSIONS: Blood pressure lowering drug interventions reduced the risk of stroke recurrence in stroke survivors. Available data did not allow to verify whether such benefit depends on initial blood pressure level. More data are needed before considering antihypertensive therapy in normotensive patients at high cerebrovascular risk.

Aged↗
PubMed1997

Predictive value of clinic blood pressure variability for pressure changes during placebo in elderly hypertensives.

OBJECTIVES: Syst-China is the ongoing placebo-controlled double-blind outcome trial in older (aged 60 years or more) Chinese patients with isolated systolic hypertension (systolic blood pressure 160-219 mmHg and diastolic blood pressure < 95 mmHg). This article is based on the data accumulated until 31 August 1992. Its purpose is to investigate the extent to which the variability in the clinic blood pressure readings at baseline could predict the blood pressure changes observed in the placebo arm of the trial. METHODS: From 2379 patients recruited into the trial, 728 [455 men and 273 women, aged 66.7+/-5.5 years (mean +/- SD)] were selected, because their blood pressure readings for the three run-in visits as well as 3, 6 and 12 months after random allocation were available. Overall and between-visit blood pressure variabilities at baseline were estimated from the two readings obtained with the subject seated during the first and second run-in visits. The baseline blood pressure used to calculate the blood pressure changes during follow-up was the average of the two readings during the third run-in visit. RESULTS: The blood pressure variability at baseline was larger for women than it was for men. For all of the subjects combined, the blood pressure had decreased by 4.1+/-14.4 mmHg (P < 0.001) systolic and 0.5+/-6.7 mmHg (P < 0.06) diastolic by the 3-month follow-up visit, by 8.5+/- 15.2 and 1.4+/-7.5 mmHg, respectively, after 6 months and by 10.3+/-15.7 and 1.9+/-7.9 mmHg, respectively, after 1 year (p < 0.001 for all). Stepwise multiple regression analysis showed that sex, age, alcohol intake and the blood pressure at baseline were significant determinants of the long-term (1 year) blood pressure changes. Aftger adjustment for the aforementioned covariates, the between-visit variability was a significant predictor of the changes in the diastolic blood pressure after 1 year of placebo treatment for the men (partial r+/-SEM -0.36+/-0.12, P < 0.01) and for all of the subjects (-0.19+/-0.09, P < 0.05). For men, the partial regression coefficient between the overall variability and the changes in the diastolic blood pressure also attained statistical significance (-0.39+/- 0.14, P < 0.01). CONCLUSION: For older Chinese patients with isolated systolic hypertension, in particular for men, a higher blood pressure variability at baseline was associated with a larger decrease in diastolic blood pressure during 1-year follow-up on placebo, explaining up to 2% of the variance of the observed changes. Similar associations were not observed for systolic blood pressure.

Journal Article↗
PubMed1996

Ambulatory blood pressure monitoring in clinical trials.

Ambulatory blood pressure monitoring is increasingly used in clinical trials. The preliminary threshold values proposed for diagnosing hypertension and adjusting treatment based on ambulatory monitoring cannot yet be widely recommended because they have not been validated in prospective studies. The trough-to-peak or surface ratios may be useful instruments for assessing the duration of action of antihypertensive drugs. Trials with ambulatory monitoring just as clinical experiments based on conventional sphygmomanometry need to be properly controlled, because ambulatory blood pressure measurement is not completely devoid of a placebo effect. Ambulatory compared with conventional blood pressure measurements are characterized by higher reproducibility which makes it possible to reduce sample size in cross-over but not in parallel group trials. Finally, ambulatory monitors used in clinical research should have successfully passed one of the standardized validation protocols.

Blood Pressure↗
PubMed1996

Potassium chloride pulse enhances mitogen-activated protein kinase activity in rat hippocampal slices.

Mitogen-activated protein (MAP) kinases have been implicated in multiple responses to extracellular stimuli. In this study we show that MAP kinase activity is enhanced after a KCl pulse. This activation correlates with an increased tyrosine phosphorylation of a 42-kDa protein as determined by antiphosphotyrosine immunoblot. The same band is found in an anti-MAP kinase immunoblot. Activity is enhanced within 1 min, reaches a maximum at 2 min, and returns to basal level after 10 min. A second peak of activity is observed between 12 and 30 min. The activation is completely blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), showing the involvement of the AMPA type of glutamate receptor. Partial inhibition of MAP kinase activation by 2-amino-5-phosphonovalerate (APV) also shows the involvement of the NMDA receptor. Because the KCl pulse used induces long-term potentiation (LTP) in rat hippocampal slice, we conclude that MAP kinase may be involved in neuronal transduction events leading to LTP.

2-Amino-5-phosphonovalerate↗