82-rubidium positron emission tomography determined myocardial flow reserve and outcomes following cardiac revascularisation - A multicentre registry study.

BACKGROUND: Finding patients with chronic coronary syndromes (CCS) whom revascularization could benefit, is complicated. Myocardial flow reserve (MFR), a measurement of myocardial perfusion, has proven prognostic value on survival and risk of major adverse cardiac events (MACE). We investigated if MFR identifies who may benefit from revascularization. METHODS: Among 7462 patients from Danish hospitals examined with 82Rb PET between January 2018 and August 2020, patients with ≥5% reversible perfusion defects were followed for MACE and all-cause mortality. Associations between revascularisation (within 90 days) and outcomes according to MFR (< and ≥ 2) was assessed by Cox regression adjusted by inverse probability weighting for demographics, cardiovascular risk factors, comorbidities, and 82Rb PET variables. RESULTS: Of 1806 patients with ≥5% reversible perfusion defect, 893 (49%) had MFR < 2 and 491 underwent revascularisation (36.6% in MFR < 2 versus 17.9% MFR ≥ 2, p < 0.001). During a median follow-up of 37.0 [31.0-45.8 IQR] months, 251 experienced a MACE and 173 died. Revascularisation was associated with lower adjusted risk of all-cause mortality (hazard ratio [HR], 0.51 [95% CI, 0.30-0.88], p = 0.015) and MACE (HR, 0.54 [0.33-0.87], p = 0.012) in patients with MFR < 2 but not MFR ≥ 2 for all-cause mortality (HR 1.33 [0.52-3.40], p = 0.542) and MACE (HR 1.50 [0.79-2.84], p = 0.211). MFR significantly modified the association between revascularisation and MACE, but not all-cause mortality (interaction p-value 0.021 and 0.094, respectively). CONCLUSIONS: Revascularization was associated with improved prognosis among patients with impaired MFR. No association was seen in patients with normal MFR. In patients with regional ischemia, MFR may identify patients with a prognostic benefit from revascularization.

Improved two-year outcomes after drug-eluting versus bare-metal stent implantation in women and men with large coronary arteries: importance of vessel size.

OBJECTIVES: To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels. METHODS: All 2314 BASKET-PROVE patients randomized to DES versus BMS were followed for 2 years with a primary endpoint of major adverse cardiac events (MACE: cardiac death, non-fatal myocardial infarction, target-vessel revascularization). Cox proportional hazard models were used to evaluate the relative risk for women and men, respectively. All comparisons were adjusted for vessel size. RESULTS: Age, risk factors and complexity of coronary artery disease differed between women and men. DES reduced MACE rates at 2 years compared to BMS--in women: 4% vs. 15%, p<0.0001 with a hazard ratio (HR) of 0.27 (0.15-0.51), and men: 6% vs. 10%, p=0.003 (HR=0.60 (0.43-0.84)), respectively. The association persisted in both women (HR=0.25 (0.13-0.46)) and men (HR=0.60 (0.42-0.84)) following multivariable adjustments. A significant gender-treatment interaction was present (p=0.02). The reduced risk of MACE following DES vs. BMS implantation was present until 6 months in both women (HR=0.15 (0.06-0.36)) and men (HR=0.32 (0.17-0.59)) and remained significant until 2 years in women (HR=0.36 (0.15-0.87)), but not in men (HR=0.87 (0.49-1.55)). CONCLUSIONS: In women and men with similarly sized large coronary arteries, DES reduced 2-year MACE rates compared to BMS, but the significant gender-treatment interaction indicated a greater benefit of DES in women. Thus, factors other than vessel size seem to determine this gender difference.

Pulse pressure and systolic night-day ratio interact in prediction of macrovascular disease in patients with type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease (CVD). We examined the predictive ability of 24-hour ambulatory pulse pressure (24-h PP), ambulatory arterial stiffness index (AASI) and diurnal blood pressure (BP) parameters for fatal and non-fatal CVD in patients with type 2 diabetes mellitus. A total of 108 patients with type 2 diabetes mellitus (mean duration 6.6 years) were followed for 9.5 (0.5-14.5) years. At baseline, all patients underwent ambulatory BP monitoring. During follow-up, 45 patients had cardiovascular (CV) events (35 non-fatal and 10 fatal). In bivariate analysis, events during follow-up were predicted by 24-h PP (P<0.01), AASI, 24-h systolic BP and systolic and diastolic night-day BP ratio (P<0.05 for all). In Cox regression analysis adjusted for established risk markers, only 24-h PP and systolic night-day BP ratio predicted CV events, P<0.05 for both. A significant interaction between the two parameters was found, P<0.05; thus, the higher the systolic night-day ratio, the greater the increase in hazard ratio (HR) per mmHg increase in 24-h PP and vice versa. A combined 10 mmHg increase in 24-h PP and 10%-point increase in systolic night-day ratio from the 25th percentile increased the adjusted HR (95% confidence interval) for CV events with 1.29 (0.53; 3.12), whereas a similar increase from the 75th percentile increased the HR with 4.2 (1.54; 11,51). Our study showed that 24-h PP and systolic night-day ratio interact as predictors of CV events in type 2 diabetes patients, and should be considered in conjunction when evaluating the risk of CVD.

Ambulatory pulse pressure, decreased nocturnal blood pressure reduction and progression of nephropathy in type 2 diabetic patients.

AIMS/HYPOTHESIS: We followed type 2 diabetic patients over a long period to evaluate the predictive value of ambulatory pulse pressure (PP) and decreased nocturnal BP reduction (non-dipping) for nephropathy progression. METHODS: Type 2 diabetic patients (n = 112) were followed for an average of 9.5 (range 0.5-14.5) years. At baseline, all patients underwent 24 h ambulatory BP measurement. Urinary albumin excretion rate was evaluated by three urinary albumin:creatinine ratio measurements at baseline and follow-up. RESULTS: At baseline, patients who subsequently progressed to a more advanced nephropathy stage (n = 35) had reduced diastolic night/day BP variation and higher 24 h systolic BP and PP values; they also had more advanced nephropathy and were more likely to smoke than those with no progression of nephropathy (n = 77). In a Cox regression analysis, independent predictors of nephropathy progression were 24 h PP (p < 0.01), diastolic night:day BP ratio (p = 0.02) and smoking (p = 0.02). The adjusted hazards ratio (95% CI) for each mmHg increment in 24 h PP was 1.04 (1.01-1.07), whereas the adjusted hazards ratio (95% CI) for each 1% increase in diastolic night:day BP ratio was 1.06 (1.01-1.11). Only one of 33 patients (3.0%) with both a diastolic night:day BP ratio and a 24 h PP below the median progressed, whereas 17 of 32 patients (53.1%) with both a diastolic night:day BP ratio and a 24 h PP equal to or above the median progressed to a more advanced nephropathy stage (p < 0.001). CONCLUSIONS/INTERPRETATION: Ambulatory PP, impaired nocturnal BP decline and smoking are strong, independent predictors of nephropathy progression in type 2 diabetic patients.

Activation of brain regions vulnerable to Alzheimer's disease: the effect of mild cognitive impairment.

This study examined the functionality of the medial temporal lobe (MTL) and posterior cingulate (PC) in mild cognitive impairment amnestic type (MCI), a syndrome that puts patients at greater risk for developing Alzheimer disease (AD). Functional MRI (fMRI) was used to identify regions normally active during encoding of novel items and recognition of previously learned items in a reference group of 77 healthy young and middle-aged adults. The pattern of activation in this group guided further comparisons between 14 MCI subjects and 14 age-matched controls. The MCI patients exhibited less activity in the PC during recognition of previously learned items, and in the right hippocampus during encoding of novel items, despite comparable task performance to the controls. Reduced fMRI signal change in the MTL supports prior studies implicating the hippocampus for encoding new information. Reduced signal change in the PC converges with recent research on its role in recognition in normal adults as well as metabolic decline in people with genetic or cognitive risk for AD. Our results suggest that a change in function in the PC may account, in part, for memory recollection failure in AD.

Left ventricular dysfunction in hypertensive patients with Type 2 diabetes mellitus.

AIMS: To characterize left ventricular function in hypertensive patients with Type 2 diabetes and normal ejection fraction, and to relate these findings to pathogenic factors and clinical risk markers. METHODS: We examined 70 hypertensive patients with Type 2 diabetes mellitus with ejection fraction > 0.55 and fractional shortening > 0.25, all without any cardiac symptoms. Thirty-five non-diabetic subjects served as control subjects. Left ventricular longitudinal function was examined by tissue Doppler derived myocardial strain rate and peak systolic velocities. RESULTS: Hypertensive patients with diabetes had a significantly higher systolic strain rate (-1.1 +/- 0.3 s(-1) vs. -1.6 +/- 0.3 s(-1), P < 0.001) and lower systolic peak velocities (3.3 +/- 1.0 vs. 5.6 +/- 1.0 cm/s, P < 0.001) compared with control subjects. Myocardial systolic strain rate correlated significantly to left ventricular mass (r = 0.40, P < 0.01) and to both HbA1c (r = 0.43, P < 0.01), and fructosamine (r = 0.40, P < 0.01), but was not related to serum levels of carboxymethyllysine, albuminuria, blood pressure (dipping/non-dipping), or oral hypoglycaemic therapy. Patients with diastolic dysfunction had significantly higher levels of urine albumin [21.0 (5-2500) mg/l, vs. 9.5 (1-360), P < 0.01], heart rate (78 +/- 13 vs. 67 +/- 10 b.p.m., P < 0.005), and seated diastolic blood pressure (85 +/- 6 vs. 81 +/- 7 mmHg, P < 0.05) and non-dipping diastolic blood pressure was more frequent. CONCLUSIONS: Long axis left ventricular systolic function was significantly decreased in hypertensive patients with Type 2 diabetes mellitus, and is associated with hyperglycaemia and left ventricular hypertrophy. Diastolic dysfunction was closely related to increased diastolic blood pressure, non-dipping and increased urinary albumin excretion.

Effects of metoprolol on QT interval and QT dispersion in Type 1 diabetic patients with abnormal albuminuria.

AIMS/HYPOTHESIS: The excess mortality in diabetes is mainly due to cardiovascular causes and almost confined to patients with abnormal albuminuria. Compared to healthy subjects, diabetic patients have a prolonged QT interval and increased QT dispersion. In non-diabetic subjects, as well as in Type 1 diabetic patients with overt nephropathy, a prolonged QT interval and increased QT dispersion are associated with cardiac morbidity and mortality. There is an increasing number of studies on effects of beta blocker treatment on QT interval and QT dispersion in non-diabetic subjects. In contrast, there are no studies on the effects of beta blocker treatment on QT interval and QT dispersion in patients with diabetes. The aim of our study was to describe the effects of metoprolol treatment on QT interval and QT dispersion in a group of well-characterised Type 1 diabetic patients with elevated urine albumin excretion. METHODS: We studied the effects of 6 weeks of treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in a randomised, placebo-controlled, double blind, crossover trial including 20 Type 1 diabetic patients. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, 24-h ambulatory blood pressure recording and 24-h fractionated urine collections. On days of investigation 12-lead electrocardiograms were recorded and autonomic tests performed. RESULTS: We found strong associations between both daytime and night-time blood pressure and heart-rate-corrected QT interval dispersion (QTc dispersion). Heart rate variability parameters indicating sympathetic and parasympathetic modulation showed strong correlations with heart-rate-corrected QT interval (QTc interval) and with QTc dispersion. Beta blocker treatment caused a decrease in QTc interval but no change in QTc dispersion. CONCLUSIONS/INTERPRETATION: This study is the first to address the QTc interval and QTc dispersion in Type 1 diabetic patients treated with metoprolol. Beta blocker treatment caused a decrease in QTc interval but no change in QTc dispersion. These results may in part explain the pronounced cardioprotective effect of beta blocker treatment in diabetic patients with cardiovascular disease.

Effects on heart rate variability of metoprolol supplementary to ongoing ACE-inhibitor treatment in Type I diabetic patients with abnormal albuminuria.

AIMS/HYPOTHESIS: Diabetic nephropathy is associated with a high risk of cardiac mortality including sudden death. This is presumably related to an imbalance between sympathetic and parasympathetic tone resulting in a decreased heart rate variability (HRV). In non-diabetic patients a decreased HRV is known to be a strong predictor of cardiovascular death. Studies in non-diabetic patients have shown that beta-blockers improve HRV parameters known to reflect parasympathetic function. The aim of our study was to investigate effects of additional beta-blocker treatment on: cardiac autonomic function, blood pressure, and urine albumin excretion in ACE-inhibitor treated Type I (insulin-dependent) diabetes mellitus patients with abnormal albuminuria. METHODS: We studied the effects of 6 weeks treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in 20 patients participating in a randomised, placebo controlled, double blind, crossover trial. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, 24-h ambulatory blood pressure recording, and 24-h fractionated urine collections. Heart rate variability was assessed by four different methods; ambulatory HRV analysis was carried out by spectral and time domain analysis, and on days of investigation short-term spectral analysis and bed-side tests were carried out. RESULTS: Metoprolol treatment improved in vagal tone assessed by short-term spectral analysis. The 24-h ambulatory HRV analysis showed improvement in some parameters reflecting vagal function. A minor decrease in daytime diastolic blood pressure was shown, no alterations in diurnal variation of blood pressure or urine albumin excretion were observed. CONCLUSION/INTERPRETATION: These preliminary findings indicate that beta-blocker treatment could improve autonomic function in Type I diabetic patients with abnormal albuminuria and an associated high risk of cardiovascular disease.

What is hypertension in diabetes? Ambulatory blood pressure in 137 normotensive and normoalbuminuric Type 1 diabetic patients.

AIMS: To establish reference data for ambulatory blood pressure (AMBP) in normotensive, normoalbuminuric Type 1 diabetic patients and characterize the relation to clinic blood pressure (BP). To evaluate the statement of the third working party of the British Hypertension Society (BHS) that a target clinic BP in diabetes < 140/80 corresponds to a target day-time AMBP < 130/75 mmHg. PATIENTS AND METHODS: AMBP were performed in 172 normoalbuminuric, adult Type 1 diabetic patients, who had never received anti-hypertensive drugs. Clinic BP was determined as the mean of at least three auscultatory (Hawskley random zero manometer) and as the mean of at least three oscillometric (Spacelabs) BP values obtained just prior to ambulatory monitoring. Five patients with more than three missing hours/24 h were excluded. RESULTS: For 30 patients auscultatory clinic BP exceeded 140 mmHg systolic and/or 90 mmHg diastolic. For the remaining 137 normotensive patients day-time AMBP was 125.7/77.2 mmHg and oscillometric clinic BP was 125.3/76.5 mmHg (mean difference 0.3/0.7 mmHg; 95% confidence interval (CI) -0.9 to 1.5/-0.3 to 1.7 mmHg, P = 0.6/P = 0.2). Sixty-five percent of the patients had a diastolic day-time AMBP > 75 mmHg. CONCLUSIONS: Clinic BP and day-time AMBP measured by the same method were indistinguishable. The target for day-time diastolic AMBP (< 75 mmHg) proposed by the BHS is too low and is based on the misconception that in normotensive subjects day-time AMBP is lower than clinic BP. If the BHS guidelines are strictly adhered to, the consequence may be overtreatment in patients with normoalbuminuria and no end organ damage.

Increased QTc dispersion is related to blunted circadian blood pressure variation in normoalbuminuric type 1 diabetic patients.

A reduced nocturnal fall in blood pressure (BP) and increased QT dispersion both predict an increased risk of cardiovascular events in diabetic as well as nondiabetic subjects. The relationship between these two parameters remains unclear. The role of diabetic autonomic neuropathy in both QT dispersion and circadian BP variation has been proposed, but data have been conflicting. The aim of the present study was to describe associations between QT dispersion and circadian BP variation as well as autonomic function in type 1 diabetic patients. In 106 normoalbuminuric (urinary albumin excretion <20 microg/min) normotensive patients, we performed 24-h ambulatory BP (Spacelabs 90207) and short-term (three times in 5 min) power spectral analysis of RR interval oscillations, as well as cardiovascular reflex tests (deep breathing test, postural heart rate, and BP response). No patient had received (or had earlier received) antihypertensive or other medical treatment apart from insulin. In a resting 12-lead electrocardiogram, the QT interval was measured by the tangent method in all leads with well-defined T-waves. The measurement was made by one observer blinded to other data. The QT interval was corrected for heart rate using Bazett's formula. The QTc dispersion was defined as the difference between the maximum and the minimum QTc interval in any of the 12 leads. When comparing patients with QTc dispersion below and above the median (43 ms), the latter had significantly higher night BP (114/67 vs. 109/62 mmHg, P < 0.003/P < 0.001), whereas day BP was comparable (129/81 vs. 127/79 mmHg). Diurnal BP variation was blunted in the group with QTc dispersion >43 ms with significantly higher night/day ratio, both for systolic (88.8 vs. 86.2%, P < 0.01) and diastolic (83.1 vs. 79.5%, P < 0.01) BP. The association between QTc dispersion and diastolic night BP persisted after controlling for potential confounders such as sex, age, duration of diabetes, urinary albumin excretion, and HbA1c. Power spectral analysis suggested an altered sympathovagal balance in patients with QTc dispersion above the median (ratio of low-frequency/high-frequency power: 1.0 vs. 0.85, P < 0.01). In normoalbuminuric type 1 diabetic patients, increased QTc dispersion is associated with reduced nocturnal fall in BP and an altered sympathovagal balance. This coexistence may be operative in the ability of these parameters to predict cardiovascular events.

No deleterious effects of tight blood glucose control on 24-hour ambulatory blood pressure in normoalbuminuric insulin-dependent diabetes mellitus patients.

Intensive therapy aiming at near normalization of glucose levels effectively delays the onset and slows the progression of complications in insulin-dependent diabetes mellitus (IDDM) and is recommended in most patients. However, in a recent report, intensive insulin treatment was found to be associated with deleterious effects on nocturnal blood pressure (BP), the proposed mechanisms being subclinical nocturnal hypoglycemia or hyperinsulinemia. The aim of the present study was to evaluate the association between glycemic control, insulin dose, and 24-h ambulatory BP (AMBP) in a group of well-characterized IDDM patients. Twenty-four-h AMBP was measured in 123 normoalbuminuric [urinary albumin excretion (UAE) < 20 microg/min] IDDM patients using an oscillometric technique (SpaceLabs 90207) with readings at 20-min intervals. UAE was measured by RIA and expressed as geometric mean of three overnight collections made within 1 week. Tobacco use and level of physical activity was assessed by questionnaire. HbA1c was determined by high-pressure liquid chromatography (nondiabetic range, 4.4-6.4%), and patients were stratified into quartiles according to HbA1c levels. Mean HbA1c values in the four groups were 7.0% (n = 31), 8.0% (n = 31), 8.6% (n = 31), and 9.7% (n = 30). The groups were comparable regarding age, gender, diabetes duration, body mass index, UAE, smoking status, and physical activity. AMBP levels were almost identical in the HbA1c quartiles with night values of (increasing HbA1c order): 110/63, 112/66, 112/66, and 113/65 mm Hg (P = 0.69/P = 0.32). There was no association between tight glucose control and higher nocturnal BP or a more blunted circadian BP variation. On the contrary, a weak positive correlation between night to day ratios of mean arterial BP and HbA1c values was found (r = 0.26, P = 0.005), i.e. blunted circadian BP variation is most frequent in patients with high HbA1c values. Neither did we find doses of insulin to be associated with night BP (r = 0.04, P = 0.68). Tight blood glucose control is not associated with deleterious effects on 24-h AMBP in normoalbuminuric IDDM patients. Intensive therapy can be implemented without concerns of inducing high nocturnal BP and accelerating diabetic complications.

Characteristics and prognosis of normoalbuminuric type 1 diabetic patients.

Intervention in type 1 diabetic patients with increased urinary albumin excretion (UAE) represents a great step forward in modern diabetology. At the moment, the consensus calls for antihypertensive treatment in normotensive type 1 diabetic patients with persistent microalbuminuria. However, recent data indicate that substantial pathophysiological changes have already taken place at the microalbuminuric stage. Thus, prevention of progression from normo- to microalbuminuria would be a major clinical turning point. A considerable number of potential risk factors for progression to microalbuminuria have been proposed, among which are blood pressure elevation and disturbancies in circadian blood pressure variation. We performed 24-h ambulatory blood pressure (AMBP) monitoring in 115 normoalbuminuric (UAE < 20 micrograms/min) patients, along with performing an assessment of circadian blood pressure and heart rate (HR) variation and a short-term power spectral analysis of RR interval oscillations. Patients with UAE above the median had significantly higher systolic and diastolic AMBP compared to the low normoalbuminuric group. The difference in blood pressure between the two groups was most pronounced for the night blood pressure (P < 0.01 and 0.02). A positive correlation between UAE and circadian variation (described as diastolic night/day ratio) was present--that is, the higher the normoalbuminuria, the more blunted the night/day ratio. The patients characterized by a combination of high-normal UAE and blunted circadian variation also proved to have significantly higher HbA1c values, higher 24-h mean arterial blood pressure, and lower vagal activity. In conclusion, high-normal UAE, poor metabolic control, and cigarette smoking are at present the only established risk factors for progression from normo- to microalbuminuria. However, new data emphasizes the close relation between blood pressure and albumin excretion. Pathophysiological abnormalities (poorer glycemic control, higher blood pressure, and attenuated vagal activity) tend to cluster in patients characterized by high-normal UAE and blunted circadian variation of blood pressures, and this patient group might constitute a putative high-risk group.

Effect of a pediatric trauma response team on emergency department treatment time and mortality of pediatric trauma victims.

OBJECTIVE: Delay in the provision of definitive care for critically injured children may adversely effect outcome. We sought to speed care in the emergency department (ED) for trauma victims by organizing a formal trauma response system. DESIGN: A case-control study of severely injured children, comparing those who received treatment before and after the creation of a formal trauma response team. SETTING: A tertiary pediatric referral hospital that is a locally designated pediatric trauma center, and also receives trauma victims from a geographically large area of the Western United States. SUBJECTS: Pediatric trauma victims identified as critically injured (designated as "trauma one") and treated by a hospital trauma response team during the first year of its existence. Control patients were matched with subjects by probability of survival scores, and were chosen from pediatric trauma victims treated at the same hospital during the year preceding the creation of the trauma team. INTERVENTIONS: A trauma response team was organized to respond to pediatric trauma victims seen in the ED. The decision to activate the trauma team (designation of patient as "trauma one") is made by the pediatric emergency medicine (PEM) physician before patient arrival in the ED, based on data received from prehospital care providers. Activation results in the notification and immediate travel to the ED of a pediatric surgeon, neurosurgeon, emergency physician, intensivist, pharmacist, radiology technician, phlebotomist, and intensive care unit nurse, and mobilization of an operating room team. Most trauma one patients arrived by helicopter directly from accident scenes. OUTCOME MEASURES: Data recorded included identifying information, diagnosis, time to head computerized tomography, time required for ED treatment, admission Revised Trauma Score, discharge Injury Severity Score, surgical procedures performed, and mortality outcome. Trauma Injury Severity Score methodology was used to calculate the probability of survival and mortality compared with the reference patients of the Major Trauma Outcome Study, by calculation of z score. RESULTS: Patients treated in the ED after trauma team initiation had statistically shorter times from arrival to computerized tomography scanning (27 +/- 2 vs 21 +/- 4 minutes), operating room (63 +/- 16 vs 623 +/- 27 minutes) and total time in the ED (85 +/- 8 vs 821 +/- 9 minutes). Calculation of z score showed that survival for the control group was not different from the reference population (z = -0.8068), although survival for trauma-one patients was significantly better than the reference population (z = 2.102). CONCLUSION: Before creation of the trauma team, relevant specialists were individually called to the ED for patient evaluation. When a formal trauma response team was organized, time required for ED treatment of severe trauma was decreased, and survival was better than predicted compared with the reference Major Trauma Outcome Study population.

Effects of smoking on 24-h ambulatory blood pressure and autonomic function in normoalbuminuric insulin-dependent diabetes mellitus patients.

Smoking is an important risk factor for the development and progression of diabetic nephropathy. The mechanisms by which smoking increases albuminuria and promotes nephropathy are unknown. Considering the acute pressor effect of smoking and the close association between blood pressure elevation and development of diabetic nephropathy, blood pressure increase might be implicated in the association between smoking and diabetic nephropathy. However, among nondiabetics, smokers have repeatedly been found to have lower blood pressure than nonsmokers. This is possibly mediated by an autonomic adjustment to sustained sympathetic stimulation by nicotine. Impaired modulation of the sympathovagal activity has been described in diabetes. In diabetic patients, the effect of smoking on blood pressure and autonomic function remains unclarified. We examined 24-h ambulatory blood pressure (oscillometric technique) and autonomic function (short-term power spectral analysis as well as conventional tests) in 24 smokers and 24 nonsmokers matched for sex, age, and diabetes duration. All patients were normoalbuminuric insulin-dependent diabetes mellitus patients. Smoking status was assessed by questionnaire with confirmatory determinations of urinary cotinine. Diabetic smokers had significantly higher 24-h mean arterial blood pressure (94+/-6.7 mm Hg compared to diabetic nonsmokers 90+/-5.8 mm Hg, P = .04) including higher diastolic nighttime blood pressure (68+/-7.3 mm Hg v 64+/-5.2 mm Hg, P = .03). Smokers also had significantly higher 24-h heart rate (80+/-7.2 compared to 72+/-9.2 beats/min, P < .001). In addition, smoking was associated with significantly reduced short-term RR interval variability (supine low frequency component) (5.45+/-1.29 ln ms2 in smokers compared to 6.31+/-1.11 ln ms2 in nonsmokers, P < .02), as well as reduced brake index (33.5+/-14.5 in smokers v 42.1+/-16.0 in nonsmokers, P < .05). Diabetic smokers have significantly higher 24-h blood pressure compared to diabetic nonsmokers. This finding, contrasting the effect of smoking among nondiabetics, is possibly mediated by coexisting abnormal postural responses in autonomic cardiac regulation in diabetic smokers. Blood pressure elevation, persisting throughout 24 h, might be operative in the association between smoking and development of diabetic nephropathy.

24-h ambulatory blood pressure and retinopathy in normoalbuminuric IDDM patients.

The role of blood pressure elevation in the incidence and progression of diabetic retinopathy is not clearly established and results have been conflicting. Blood pressure and urinary albumin excretion (UAE) are closely related. In order to evaluate the independent relationship between retinopathy and blood pressure elevation, precise information on UAE is essential, as confounding by renal disease (incipient or overt), cannot otherwise be excluded. The aim of the present study was to evaluate the association between diabetic retinopathy and 24-h ambulatory blood pressure (AMBP) in a group of well-characterized normoalbuminuric IDDM patients. In 65 normoalbuminuric (UAE < 20 microg/min) IDDM patients we performed 24-h AMBP (Spacelabs 90207) with readings at 20-min intervals. Fundus photographs were graded independently by two experienced ophthalmologists. UAE was measured by RIA and expressed as geometric mean of three overnight collections made within 1 week. HbA1c was determined by HPLC. Tobacco use and level of physical activity were assessed by questionnaire. Fifteen patients had no detectable retinal changes [grade 1], 35 had grade 2 retinopathy; and 15 had more advanced retinopathy [grade 3-6]. Diastolic night blood pressure was significantly higher in patients with diabetic retinopathy compared to patients without retinopathy (68 +/- 8 mmHg [grade 3-6] and 65 +/- 6 mmHg [grade 2], compared to 61 +/- 4 mmHg [grade 1], p = 0.02). Diurnal blood pressure variation was significantly blunted in the patients with retinopathy as indicated by a higher night/day ratio of diastolic blood pressure (84.6% +/- 4 [grade 3-6], and 81.2% +/- 6 [grade 2] compared to 79.1% +/- 4 [grade 1], p = 0.01). Heart rate tended to be higher in patients in group 2 and 3-6 compared to patients without retinopathy with p values of 0.07 and 0.11 for day-time and 24 h values, respectively. Mean HbA1c increased significantly with increasing levels of retinopathy (p < 0.01). Patients were similar regarding sex, age, tobacco use, and level of physical activity. Notably, UAE was almost identical in the three groups (5.0 x /divided by 1.7 [grade 1], 3.9 x /divided by 1.8 [grade 2], and 5.1 x /divided by 1.6 microg/min [grade 3-6]). In conclusion, night blood pressure is higher and circadian blood pressure variation blunted in patients with retinopathy compared to patients without retinopathy despite strict normoalbuminuria and similar UAE levels in the groups compared. Our data suggest that the association between blood pressure and diabetic retinopathy is present also when coexisting renal disease is excluded. Disturbed diurnal variation of blood pressure is a pathophysiological feature related to the development of both retinopathy and nephropathy in IDDM patients.

24-h blood pressure and autonomic function is related to albumin excretion within the normoalbuminuric range in IDDM patients.

Significant changes in both blood pressure, autonomic function and kidney ultrastructure are observed in insulin-dependent diabetic (IDDM) patients with microalbuminuria. Intervention strategies are evaluated at even earlier stages of disease. Identification of patients at risk of developing microalbuminuria must be based on a thorough knowledge of the relations between key pathophysiological parameters in patients with normoalbuminuria. The aim of the present study was to characterize the interactions of urinary albumin excretion (UAE), 24-h ambulatory blood pressure (AMBP), and sympathovagal balance in a large group of normoalbuminuric IDDM patients. In 117 normoalbuminuric (UAE < 20 micrograms/min) patients we performed 24-h AMBP (Spacelabs 90207), with assessment of diurnal blood pressure and heart rate (HR) variation, and short-term (three times 5 min) power spectral analysis of RR interval oscillations, as well as cardiovascular reflex tests (HR variation to deep breathing, postural HR and blood pressure response). Patients with UAE above the median (4.2 micrograms/min) had significantly higher 24-h systolic and diastolic AMBP (125 +/- 10.1/76 +/- 7.2 mmHg) compared to the low normolbuminuric group (120 +/- 8.4/74 +/- 5.1 mmHg), p < 0.01 and 0.02, respectively. Patients with UAE above the median had significantly reduced short-term RR interval variability including both the high frequency component (5.47 +/- 1.36 vs 6.10 +/- 1.43 ln ms2), and low frequency component (5.48 +/- 1.18 ln ms2 compared to 5.80 +/- 1.41 ln ms2), p < 0.02 and p = 0.04 (ANOVA). In addition, patients with high-normal UAE had reduced mean RR level (faster heart rates) 916 +/- 108 compared to 963 +/- 140 ms, p < 0.04. These differences were not explained by age, duration of diabetes, gender, level of physical activity, or cigarette smoking. HbA1c was significantly higher (8.6 +/- 1.2 vs 8.2 +/- 1.0%, p = 0.03) in the group with high normal UAE. Comparing normoalbuminuric IDDM patients with UAE above and below the median value, we found significantly higher AMBP in combination with significant differences in sympathovagal balance and significantly poorer glycaemic control in the group with high-normal albumin excretion. Our data demonstrate interactions between albumin excretion, blood pressure, autonomic function, and glycaemic status, already present in the normoalbuminuric range and may describe a syndrome indicative of later complications.