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1.
J Vet Cardiol ; 52: 1-13, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38290222

ABSTRACT

INTRODUCTION/OBJECTIVES: Spontaneous pulmonary vein (PV) activity triggers atrial fibrillation (AF) in humans. Although AF frequently occurs in horses, the origin remains unknown. This study investigated the structural and electro-anatomical properties of equine PVs to determine the potential presence of an arrhythmogenic substrate. ANIMALS, MATERIALS AND METHODS: Endocardial three-dimensional electro-anatomical mapping (EnSite Precision) using high-density (HD) catheters was performed in 13 sedated horses in sinus rhythm. Left atrium (LA) access was obtained retrogradely through the carotid artery. Post-mortem, tissue was harvested from the LA, right atrium (RA), and PVs for histological characterization and quantification of ion channel expression using immunohistochemical analysis. RESULTS: Geometry, activation maps, and voltage maps of the PVs were created and a median of four ostia were identified. Areas of reduced conduction were found at the veno-atrial junction. The mean myocardial sleeve length varied from 28 ± 13 to 49 ± 22 mm. The PV voltage was 1.2 ± 1.4 mV and lower than the LA (3.4 ± 0.9 mV, P < 0.001). The fibrosis percentage was higher in PV myocardium (26.1 ± 6.6%) than LA (14.5 ± 5.0%, P = 0.003). L-type calcium channel (CaV1.2) expression was higher in PVs than LA (P = 0.001). T-type calcium channels (CaV3.3), connexin-43, ryanodine receptor-2, and small conductance calcium-activated potassium channel-3 was expressed in PVs. CONCLUSIONS: The veno-atrial junction had lower voltages, increased structural heterogeneity and areas of slower conduction. Myocardial sleeves had variable lengths, and a different ion channel expression compared to the atria. Heterogeneous properties of the PVs interacting with the adjacent LA likely provide the milieu for re-entry and AF initiation.


Subject(s)
Atrial Fibrillation , Pulmonary Veins , Animals , Horses , Pulmonary Veins/pathology , Atrial Fibrillation/veterinary , Atrial Fibrillation/pathology , Female , Male , Horse Diseases/pathology , Heart Atria/pathology
2.
J Hum Hypertens ; 31(3): 178-188, 2017 03.
Article in English | MEDLINE | ID: mdl-27511476

ABSTRACT

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.


Subject(s)
Antihypertensive Agents/administration & dosage , Benzimidazoles/administration & dosage , Calcium Channel Blockers/administration & dosage , Hypertension/drug therapy , Nifedipine/administration & dosage , Tetrazoles/administration & dosage , Biphenyl Compounds , Blood Pressure/drug effects , Drug Therapy, Combination , Female , Humans , Male , Middle Aged
3.
J Clin Pharm Ther ; 41(6): 695-702, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27670639

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: The nifedipine gastrointestinal therapeutic system (GITS)/candesartan cilexetil (N/C) combination was demonstrated to be an effective, well-tolerated antihypertensive therapy in a short-term study. The current study investigated the long-term safety and efficacy of a fixed-dose combination (FDC) of N/C therapy in moderate-to-severe essential hypertension. METHODS: A multinational, 70-centre, open-label study of N/C treatment for 28 or 52 weeks at a target dose of N60 mg/C32 mg. The primary assessment included the incidence of treatment-emergent adverse events (TEAEs). Efficacy assessments included change from baseline in systolic and diastolic blood pressure (BP). RESULTS AND DISCUSSION: A total of 508 patients were enrolled, with 417 (82·1%) completing week 28 of treatment. Of these, 200 patients continued treatment, as planned, to week 52, with 193 (96·5%) completing this period. At least one TEAE or drug-related TEAE were reported in 76·8% and 45·3% patients up to week 28, and in 80·7% and 46·9% up to week 52/end of study. Most TEAEs and drug-related TEAEs to week 52 (93·9% and 95·4%, respectively) were mild or moderate in intensity. Rates of drug-related serious AEs were low (0·6%). TEAE-related discontinuations occurred in 10% patients before week 28 and in no additional patients thereafter. N/C provided substantial, sustained reductions in mean systolic and diastolic BP from baseline: 30·1 ± 18·4 and 12·8 ± 10·7 mmHg, respectively, at week 52. WHAT IS NEW AND CONCLUSIONS: Nifedipine GITS/candesartan cilexetil FDC at the target dose of 60 mg/32 mg was well tolerated for a study duration up to 52 weeks and provided sustained reductions in systolic and diastolic BP.


Subject(s)
Antihypertensive Agents/administration & dosage , Benzimidazoles/administration & dosage , Biphenyl Compounds/administration & dosage , Hypertension/drug therapy , Nifedipine/administration & dosage , Tetrazoles/administration & dosage , Aged , Blood Pressure , Drug Therapy, Combination/methods , Essential Hypertension , Female , Humans , Male , Middle Aged
4.
J Hum Hypertens ; 28(11): 663-9, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25211055

ABSTRACT

Differences in clinical effectiveness between angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in the primary treatment of hypertension are unknown. The aim of this retrospective cohort study was to assess the prevention of type 2 diabetes and cardiovascular disease (CVD) in patients treated with ARBs or ACEis. Patients initiated on enalapril or candesartan treatment in 71 Swedish primary care centers between 1999 and 2007 were included. Medical records data were extracted and linked with nationwide hospital discharge and cause of death registers. The 11,725 patients initiated on enalapril and 4265 on candesartan had similar baseline characteristics. During a mean follow-up of 1.84 years, 36,482 patient-years, the risk of new diabetes onset was lower in the candesartan group (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69-0.96, P=0.01) compared with the enalapril group. No difference between the groups was observed in CVD risk (HR 0.99, 95% CI 0.87-1.13, P=0.86). More patients discontinued treatment in the enalapril group (38.1%) vs the candesartan group (27.2%). In a clinical setting, patients initiated on candesartan treatment had a lower risk of new-onset type 2 diabetes and lower rates of drug discontinuation compared with patients initiated on enalapril. No differences in CVD risk were observed.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Benzimidazoles/therapeutic use , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/prevention & control , Enalapril/therapeutic use , Hypertension/drug therapy , Tetrazoles/therapeutic use , Aged , Biphenyl Compounds , Blood Pressure/drug effects , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/physiopathology , Incidence , Male , Middle Aged , Primary Health Care , Retrospective Studies , Risk Factors , Sweden/epidemiology , Time Factors , Treatment Outcome
5.
J Hum Hypertens ; 28(3): 150-6, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24067345

ABSTRACT

We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of 10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-µmol l(-1) increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment.


Subject(s)
Denervation , Hypertension/drug therapy , Hypertension/surgery , Kidney/innervation , Antihypertensive Agents/therapeutic use , Blood Pressure Monitoring, Ambulatory , Combined Modality Therapy , Essential Hypertension , Europe , Female , Humans , Male , Middle Aged , Treatment Outcome
6.
Diabetes Res Clin Pract ; 101(2): 201-9, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23827210

ABSTRACT

AIMS: To examine the impact of physical fitness (PF) on the association between fasting serum triglycerides (FTG) and diabetes risk and whether temporal changes in FTG predict diabetes risk in healthy middle-aged men. METHODS: FTG and PF (bicycle exercise test) were measured in 1962 men aged 40-59 years in 1972-1975 (Survey 1) and repeated in 1387 still healthy men on average 7.3 years later (Survey 2). Diabetes was diagnosed according to WHO 1985-criteria. RESULTS: During 35 years follow-up 202/1962 (10.3%) men developed diabetes. Compared with the lowest, the upper FTG tertile had a 2.58-fold (95% CI: 1.81-3.74) diabetes risk adjusted for age, fasting blood glucose and maternal diabetes, and a 2.29-fold (95%CI: 1.60-3.33) when also adjusting for PF. Compared with unchanged (±25%) FTG levels (n=664), FTG reduction of more than 25% (n=261) was associated with 56% lower (0.44; 95% CI: 0.24-0.75) diabetes risk, while FTG increase of more than 25% (n=462) was associated with similar risk. These associations were unchanged when adjusted for PF and PF change. CONCLUSIONS: High FTG-levels predicted long-term diabetes risk in healthy middle-aged men, and the association was only modestly weakened when adjusted for PF. A reduction in FTG was associated with decreased diabetes risk.


Subject(s)
Diabetes Mellitus/blood , Physical Fitness/physiology , Triglycerides/blood , Adult , Diabetes Mellitus/epidemiology , Female , Humans , Male , Middle Aged , Norway/epidemiology
7.
Diabet Med ; 30(10): 1189-97, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23587029

ABSTRACT

AIMS: Although hypertensive patients with low baseline HDL cholesterol levels have a higher incidence of diabetes mellitus, whether changing levels of HDL over time are more strongly related to the risk of new diabetes in hypertensive patients has not been examined. METHODS: Incident diabetes mellitus was examined in relation to baseline and in-treatment HDL levels in 7485 hypertensive patients with no history of diabetes randomly assigned to losartan- or atenolol-based treatment. RESULTS: During 4.7 ± 1.2 years follow-up, 520 patients (6.9%) developed new diabetes. In univariate Cox analyses, compared with the highest quartile of HDL levels (> 1.78 mmol/l), baseline and in-treatment HDL in the lowest quartile (< 1.21 mmol/l) identified patients with > 5-fold and > 9 fold higher risks of new diabetes, respectively; patients with baseline or in-treatment HDL in the 2nd and 3rd quartiles had intermediate risk of diabetes. In multivariable Cox analyses, adjusting for randomized treatment, age, sex, race, prior anti-hypertensive therapy, baseline uric acid, serum creatinine and glucose entered as standard covariates, and in-treatment non-HDL cholesterol, Cornell product left ventricular hypertrophy, diastolic and systolic pressure, BMI, hydrochlorothiazide and statin use as time-varying covariates, the lowest quartile of in-treatment HDL remained associated with a nearly 9-fold increased risk of new diabetes (hazard ratio 8.7, 95% CI 5.0-15.2), whereas the risk of new diabetes was significantly attenuated for baseline HDL < 1.21 mmol/l (hazard ratio 3.9, 95% CI 2.8-5.4). CONCLUSIONS: Lower in-treatment HDL is more strongly associated with increased risk of new diabetes than baseline HDL level.


Subject(s)
Antihypertensive Agents/therapeutic use , Cholesterol, HDL/blood , Diabetes Mellitus, Type 2/blood , Diabetic Angiopathies/blood , Hyperglycemia/blood , Hypertension/blood , Hypertrophy, Left Ventricular/blood , Aged , Atenolol/administration & dosage , Comorbidity , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/physiopathology , Diabetic Angiopathies/drug therapy , Diabetic Angiopathies/physiopathology , Female , Follow-Up Studies , Humans , Hydrochlorothiazide/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hyperglycemia/drug therapy , Hyperglycemia/physiopathology , Hypertension/drug therapy , Hypertension/physiopathology , Hypertrophy, Left Ventricular/drug therapy , Hypertrophy, Left Ventricular/physiopathology , Incidence , Losartan/administration & dosage , Male , Middle Aged , Predictive Value of Tests , Proportional Hazards Models , Risk Factors
8.
J Hum Hypertens ; 27(2): 100-6, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22336903

ABSTRACT

High intake of fruits and vegetables is associated with reduced cardiovascular risk. A number of fruits and vegetables are rich in anthocyanins, which constitute a subgroup of the flavonoids. Anthocyanins have demonstrated anti-inflammatory and anti-oxidative properties, and anthocyanin-rich interventions have indicated beneficial effects on blood pressure and other cardiovascular risk factors. We assessed whether a purified anthocyanin supplement improves cardiovascular metabolic risk factors and markers of inflammation and oxidative stress in prehypertensive participants, and whether plasma polyphenols are increased 1-3 h following intake. In all, 31 men between 35-51 years with screening blood pressure >140/90 mm Hg without anti-hypertensive or lipid-lowering medication, were randomized in a double-blinded crossover study to placebo versus 640 mg anthocyanins daily. Treatment durations were 4 weeks with a 4-week washout. High-density lipoprotein (HDL)-cholesterol and blood glucose were significantly higher after anthocyanin versus placebo treatment (P=0.043 and P=0.024, respectively). No effects were observed on inflammation or oxidative stress in vivo, except for von Willebrand factor, which was higher in the anthocyanin period (P=0.007). Several plasma polyphenols increased significantly 1-3 h following anthocyanin intake. The present study strengthens the evidence that anthocyanins may increase HDL-cholesterol levels, and this is demonstrated for the first time in prehypertensive and non-dyslipidemic men. However, no other beneficial effects in the short term were found on pathophysiological markers of cardiovascular disease.


Subject(s)
Anthocyanins/administration & dosage , Antioxidants/pharmacology , Cardiovascular Diseases/drug therapy , Inflammation/drug therapy , Oxidative Stress/drug effects , Prehypertension/drug therapy , Adult , Biomarkers , Blood Glucose , Cardiovascular Diseases/prevention & control , Cross-Over Studies , Dietary Supplements , Double-Blind Method , Humans , Lipoproteins, HDL , Male , Middle Aged , Risk Factors , Treatment Outcome
9.
J Hum Hypertens ; 27(7): 412-6, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23235366

ABSTRACT

The Global Cardiometabolic Risk Profile in Patients with hypertension disease (GOOD) survey investigated the global cardiometabolic risk profile in 3464 adult outpatients with hypertension across 289 sites in 12 European countries. The pulse pressure and heart rate profile of the survey population was evaluated according to the presence or absence of metabolic syndrome and/or type 2 diabetes mellitus. History and treatment of hypertension were not counted as criteria for metabolic syndrome as they applied to all patients. Out of the 3370 recruited patients, 1033 had metabolic syndrome and 1177 had neither metabolic syndrome nor diabetes. When compared with patients with no metabolic syndrome or diabetes, patients with metabolic syndrome had higher pulse pressure (59±14 vs. 55±14 mm Hg) and heart rate (75.2±11.0 vs. 72.5±10.0 beats per min) (P<0.001 for both), independent of the concomitant presence or absence of diabetes, despite a more prevalent use of ß-blockers. In conclusion, in hypertensive outpatients the presence of metabolic syndrome is associated with increased heart rate and pulse pressure, which may at least in part reflect increased arterial stiffness and increased sympathetic tone. This may contribute, to some extent, to explaining the increased cardiovascular risk attributed to the presence of metabolic syndrome.


Subject(s)
Blood Pressure , Heart Rate , Hypertension/physiopathology , Metabolic Syndrome/physiopathology , Aged , Analysis of Variance , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Case-Control Studies , Chi-Square Distribution , Cross-Sectional Studies , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/physiopathology , Europe/epidemiology , Female , Health Surveys , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology , Male , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Middle Aged , Outpatients , Prognosis , Risk Assessment , Risk Factors
10.
J Hum Hypertens ; 26(6): 396-404, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21544087

ABSTRACT

High intakes of flavonoids are associated with reduced cardiovascular risk, and flavonoids such as cocoa and soy protein isolate have shown beneficial effects on blood pressure (BP). Anthocyanins constitute a flavonoid subgroup consumed in regular diets, but few studies have assessed the antihypertensive potential of anthocyanins. We aimed to assess whether high concentrations of relatively pure anthocyanins reduce BP and alter cardiovascular and catecholamine reactivity to stress. A total of 31 healthy men between 35-51 years of age with screening BP >140/90 mm Hg, not on antihypertensive or lipid-lowering medication, were randomised in a double-blind crossover study to placebo versus 320-mg anthoycanins twice daily. Treatment duration was 4 weeks, with a 4-week washout. Sitting and supine BP measurements, ambulatory BP recording and stress reactivity were assessed and analyzed by a paired sample t-test. In all, 27 patients completed all visits. Sitting systolic BP (primary endpoint) was 133 mm Hg after placebo versus 135 mm Hg after anthocyanin treatment (P=0.25). Anthocyanins did neither affect semiautomatic oscillometric BP measurements in the sitting or supine position nor 24-h ambulatory BP. No significant differences in stress reactivity were found across treatment periods. Overall, we conclude that high concentrations of these relatively pure anthocyanins do not reduce BP in healthy men with a high normal BP.


Subject(s)
Anthocyanins/pharmacology , Blood Pressure/drug effects , Stress, Physiological/physiology , Stress, Psychological/physiopathology , Adult , Cross-Over Studies , Double-Blind Method , Heart Rate/drug effects , Humans , Middle Aged
11.
J Intern Med ; 271(6): 581-8, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22061296

ABSTRACT

OBJECTIVE: To determine whether a low-grade systolic murmur, found at heart auscultation, in middle-aged healthy men influences the long-term risk of aortic valve replacement (AVR) and death from cardiovascular disease (CVD). Setting and subjects. During 1972-1975, 2014 apparently healthy men aged 40-59 years underwent an examination programme including case history, clinical examination, blood tests and a symptom-limited exercise ECG test. Heart auscultation was performed under standardized conditions, and murmurs were graded on a scale from I to VI. No men were found to have grade V/VI murmurs. Participants were followed for up to 35 years. RESULTS: A total of 1541 men had no systolic murmur; 441 had low-grade murmurs (grade I/II) and 32 had moderate-grade murmurs (grade III/IV). Men with low-grade murmurs had a 4.7-fold [95% confidence interval (CI) 2.1-11.1] increased age-adjusted risk of AVR, but no increase in risk of CVD death. Men with moderate-grade murmurs had an 89.3-fold (95% CI 39.2-211.2) age-adjusted risk of AVR and a 1.5-fold (95% CI 0.8-2.5) age-adjusted increased risk of CVD death. CONCLUSIONS: Low-grade systolic murmur was detected at heart auscultation in 21.9% of apparently healthy middle-aged men. Men with low-grade murmur had an increased risk of AVR, but no increase in risk of CVD death. Only 1.6% of men had moderate-grade murmur; these men had a very high risk of AVR and a 1.5-fold albeit non-significant increase in risk of CVD death.


Subject(s)
Heart Diseases/diagnosis , Heart Murmurs/diagnosis , Heart Valve Prosthesis Implantation/statistics & numerical data , Adult , Aortic Valve Stenosis/diagnosis , Cohort Studies , Follow-Up Studies , Heart Auscultation/methods , Heart Diseases/complications , Heart Diseases/mortality , Heart Diseases/surgery , Heart Murmurs/epidemiology , Heart Murmurs/etiology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Norway/epidemiology , Odds Ratio , Physical Examination , Prevalence , Prognosis , Prospective Studies , Risk Factors
12.
J Hum Hypertens ; 25(2): 130-6, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20376078

ABSTRACT

A recent study of two widely used angiotensin receptor blockers reported a reduced risk of cardiovascular events (-14.4%) when using candesartan compared with losartan in the primary treatment of hypertension. In addition to clinical benefits, costs associated with treatment strategies must be considered when allocating scarce health-care resources. The aim of this study was to assess resource use and costs of losartan and candesartan in hypertensive patients. Resource use (drugs, outpatient contacts, hospitalizations and laboratory tests) associated with losartan and candesartan treatment was estimated in 14,100 patients in a real-life clinical setting. We electronically extracted patient data from primary care records and mandatory Swedish national registers for death and hospitalization. Patients treated with losartan had more outpatient contacts (+15.6%), laboratory tests (+13.8%) and hospitalizations (+13.8%) compared with the candesartan group. During a maximum observation time of 9 years, the mean total costs per patient were 10,369 Swedish kronor (95% confidence interval: 3109-17,629) higher in the losartan group. In conclusion, prescribing candesartan for the primary treatment of hypertension results in lower long-term health-care costs compared with losartan.


Subject(s)
Benzimidazoles , Health Care Costs , Hypertension/therapy , Losartan , Registries , Tetrazoles , Acute Coronary Syndrome/etiology , Acute Coronary Syndrome/prevention & control , Angiotensin II Type 1 Receptor Blockers/economics , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Antihypertensive Agents/economics , Antihypertensive Agents/therapeutic use , Benzimidazoles/economics , Benzimidazoles/therapeutic use , Biphenyl Compounds , Brain Ischemia/etiology , Brain Ischemia/prevention & control , Drug Costs , Hospitalization/economics , Humans , Hypertension/complications , Hypertension/economics , Hypertension/physiopathology , Long-Term Care/economics , Losartan/economics , Losartan/therapeutic use , Sweden , Tetrazoles/economics , Tetrazoles/therapeutic use
13.
J Hum Hypertens ; 25(3): 178-85, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20505749

ABSTRACT

The predictive value of changes in the severity of electrocardiographic left ventricular hypertrophy (ECG-LVH) during antihypertensive therapy remains unclear in isolated systolic hypertension (ISH). In a Losartan Intervention For Endpoint reduction in hypertension substudy, we included 1320 patients aged 54-83 years with systolic blood pressure (BP) of 160-200 mm Hg, diastolic BP <90 mm Hg and ECG-LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria, randomized to losartan- or atenolol-based treatment with a mean follow-up of 4.8 years. The composite end point of cardiovascular death, non-fatal myocardial infarction (MI) or stroke occurred in 179 (13.6%) patients. In Cox regression models controlling for treatment, Framingham risk score, as well as baseline and in-treatment BP, less severe in-treatment ECG-LVH by Cornell product and Sokolow-Lyon voltage was associated with 17 and 25% risk reduction for the composite end point (adjusted hazard ratio (HR) 0.83, 95% confidence interval (95% CI:) 0.75-0.92, P=0.001 per 1050 mm × ms (1 s.d.) lower Cornell product; and HR 0.75, 95% CI: 0.65-0.87, P<0.001 per 10.5 mm (1 s.d.) lower Sokolow-Lyon voltage). In parallel analyses, lower Cornell product and Sokolow-Lyon voltage were associated with lower risks of cardiovascular mortality and MI, and lower Sokolow-Lyon voltage with lower risk of stroke. Lower Cornell product and Sokolow-Lyon voltage during antihypertensive therapy are associated with lower likelihoods of cardiovascular events in patients with ISH.


Subject(s)
Electrocardiography , Hypertension/physiopathology , Hypertrophy, Left Ventricular/physiopathology , Myocardial Infarction/physiopathology , Stroke/physiopathology , Aged , Aged, 80 and over , Antihypertensive Agents , Atenolol/therapeutic use , Female , Follow-Up Studies , Humans , Hypertension/drug therapy , Hypertension/mortality , Hypertrophy, Left Ventricular/drug therapy , Hypertrophy, Left Ventricular/mortality , Losartan/therapeutic use , Male , Middle Aged , Myocardial Infarction/drug therapy , Myocardial Infarction/mortality , Prospective Studies , Randomized Controlled Trials as Topic , Risk , Severity of Illness Index , Smoking/epidemiology , Stroke/drug therapy , Stroke/mortality , Treatment Outcome
14.
J Hum Hypertens ; 24(8): 505-13, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20010619

ABSTRACT

Screening for hypertensive organ damage is important in assessing cardiovascular risk in hypertensive individuals. In a 20-year follow-up of normotensive and hypertensive men, signs of end-organ damage were examined, focusing on hypertensive retinopathy. In all, 56 of the original 79 men were reexamined for hypertensive organ damage, including by digital fundus photography. The diameters of the central retinal artery equivalent (CRAE) and vein were estimated and the artery-to-vein diameter ratio calculated. Components of metabolic syndrome were assessed. Fifty percent of the normotensive men developed hypertension during follow-up. Significant differences appeared in CRAE between the different blood pressure groups (P=0.025) while no differences were observed for other markers of hypertensive organ damage. There were significant relationships between CRAE and blood pressure at baseline (r=-0.466, P=0.001) and at follow-up (r=-0.508, P<0.001). A linear decrease in CRAE was observed with increasing number of components of the metabolic syndrome (beta=-3.947, R(2)=0.105, P=0.023). Retinal vascular diameters were closely linked to blood pressures and risk factors of the metabolic syndrome. The diversity in the development of hypertensive organ damage, with changes in retinal microvasculature preceding other signs of damage, should encourage more liberal use of fundus photography in assessing cardiovascular risk in hypertensive individuals.


Subject(s)
Blood Pressure , Hypertension/complications , Hypertension/physiopathology , Retinal Diseases/etiology , Retinal Diseases/physiopathology , Adult , Disease Progression , Follow-Up Studies , Hematocrit , Humans , Male , Middle Aged , Ophthalmoscopy , Outpatients , Photography , Retinal Artery/pathology , Retinal Diseases/pathology
15.
J Hum Hypertens ; 24(4): 263-73, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19890371

ABSTRACT

Although angiotensin receptor blockers have different receptor binding properties no comparative studies with cardiovascular disease (CVD) end points have been performed within this class of drugs. The aim of this study was to test the hypothesis that there are blood pressure independent CVD-risk differences between losartan and candesartan treatment in patients with hypertension without known CVD. Seventy-two primary care centres in Sweden were screened for patients who had been prescribed losartan or candesartan between the years 1999 and 2007. Among the 24 943 eligible patients, 14 100 patients were diagnosed with hypertension and prescribed losartan (n=6771) or candesartan (n=7329). Patients were linked to Swedish national hospitalizations and death cause register. There was no difference in blood pressure reduction when comparing the losartan and candesartan groups during follow-up. Compared with the losartan group, the candesartan group had a lower adjusted hazard ratio for total CVD (0.86, 95% confidence interval (CI) 0.77-0.96, P=0.0062), heart failure (0.64, 95% CI 0.50-0.82, P=0.0004), cardiac arrhythmias (0.80, 95% CI 0.65-0.92, P=0.0330), and peripheral artery disease (0.61, 95% CI 0.41-0.91, P=0.0140). No difference in blood pressure reduction was observed suggesting that other mechanisms related to different pharmacological properties of the drugs may explain the divergent clinical outcomes.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/administration & dosage , Benzimidazoles/administration & dosage , Hypertension/drug therapy , Hypertension/epidemiology , Losartan/administration & dosage , Tetrazoles/administration & dosage , Aged , Biphenyl Compounds , Blood Pressure/drug effects , Female , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Infarction/epidemiology , Myocardial Infarction/prevention & control , Myocardial Ischemia/epidemiology , Myocardial Ischemia/prevention & control , Primary Health Care/statistics & numerical data , Proportional Hazards Models , Registries , Risk Factors , Risk Reduction Behavior , Sensitivity and Specificity , Stroke/epidemiology , Stroke/prevention & control , Sweden/epidemiology
16.
Nutr Metab Cardiovasc Dis ; 19(9): 634-40, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19361968

ABSTRACT

BACKGROUND AND AIMS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome predicted outcome in the LIFE study, independently of single risk markers, including obesity, diabetes and baseline ECG left ventricular hypertrophy (LVH). We examined whether clusters of two or more metabolic abnormalities (MetAb, including obesity, high plasma glucose without diabetes, low HDL-cholesterol) in addition to hypertension were associated to levels of ECG LVH reduction comparable to that obtained in hypertensive subjects without or with only one additional metabolic abnormality (no-MetAb). METHODS AND RESULTS: We studied 5558 non-diabetic participants without MetAb (2920 women) and 1235 with MetAb (751 women) from the LIFE-study cohort. MetAb was defined by reported LIFE criteria, using partition values from the ATPIII recommendations. Time-trends of Cornell voltage-duration product (CP) over 5 years was assessed using a quadratic polynomial contrast, adjusting for age, sex, prevalent cardiovascular disease and treatment arm (losartan or atenolol). At baseline, despite similar blood pressures, CP was greater in the presence than in the absence of MetAb (p<0.0001). During follow-up, despite similar reduction of blood pressure, CP decreased less in patients with than in those without MetAb, even after adjustment for the respective baseline values (both p<0.002). Losartan was more effective than atenolol in reducing CP independently of MetAb. CONCLUSIONS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome are related to greater initial ECG LVH in hypertensive patients with value of blood pressure similar to individuals without metabolic abnormalities, and are associated with less reduction of ECG LVH during antihypertensive therapy, potentially contributing to the reported adverse prognosis of metabolic syndrome.


Subject(s)
Hypertension/epidemiology , Hypertension/metabolism , Hypertrophy, Left Ventricular/epidemiology , Hypertrophy, Left Ventricular/metabolism , Aged , Blood Glucose/metabolism , Blood Pressure/physiology , Cholesterol/blood , Cluster Analysis , Cohort Studies , Diabetes Mellitus/epidemiology , Diabetes Mellitus/metabolism , Echocardiography , Electrocardiography , Female , Follow-Up Studies , Humans , Hypertrophy, Left Ventricular/diagnostic imaging , Male , Middle Aged , Obesity/epidemiology , Obesity/metabolism , Prevalence , Risk Factors
17.
J Hum Hypertens ; 23(5): 316-24, 2009 May.
Article in English | MEDLINE | ID: mdl-19005476

ABSTRACT

The GOOD survey investigated the global cardiometabolic risk profile in adult patients with hypertension across 289 sites in four European regions (Northwest, Mediterranean, Atlantic European Mainland and Central Europe). Demographic, lifestyle, clinical and laboratory data were collected from eligible patients (n=3370) during a single clinic visit. In Central Europe, represented by Hungary, 44% of the participants had type II diabetes compared with 33% in the Atlantic European Mainland, and 26% in the Northwest and the Mediterranean regions. The prevalence of metabolic syndrome was also significantly higher in Central Europe (68%) and the Atlantic European Mainland (60%) than in the Northwest and the Mediterranean regions (50 and 52%, respectively). Fasting blood glucose, total cholesterol and triglyceride levels were all highest in Central Europe compared with the other three regions (P<0.001). In the Atlantic European Mainland, more patients had uncontrolled blood pressure (80%) compared with the other three regions (70-71%). Declared alcohol consumption was highest in the Atlantic European Mainland and exercise lowest in Central Europe. The prevalence of congestive heart failure, left ventricular hypertrophy, coronary artery disease and stable/unstable angina was higher in Central Europe compared with the other regions, whereas a family history of premature stroke or myocardial infarction, stroke, coronary revascularization and transient ischaemic attacks was all highest in the Atlantic European Mainland. These data indicate that many hypertensive patients across Europe have multiple cardiometabolic risk factors with the prevalence higher in Central Europe and the Atlantic European Mainland compared with Northwest and Mediterranean regions.


Subject(s)
Geography , Hypertension/epidemiology , Aged , Alcohol Drinking/blood , Alcohol Drinking/epidemiology , Alcohol Drinking/genetics , Angina Pectoris/blood , Angina Pectoris/epidemiology , Angina Pectoris/genetics , Blood Glucose , Cholesterol/blood , Comorbidity , Coronary Artery Disease/blood , Coronary Artery Disease/epidemiology , Coronary Artery Disease/genetics , Cross-Sectional Studies , Europe/epidemiology , Female , Health Surveys , Heart Failure/blood , Heart Failure/epidemiology , Heart Failure/genetics , Humans , Hypertension/blood , Hypertension/genetics , Hypertrophy, Left Ventricular/blood , Hypertrophy, Left Ventricular/epidemiology , Hypertrophy, Left Ventricular/genetics , Male , Metabolic Syndrome/blood , Metabolic Syndrome/epidemiology , Metabolic Syndrome/genetics , Middle Aged , Pedigree , Prevalence , Risk Factors , Triglycerides/blood
18.
J Hum Hypertens ; 22(8): 520-7, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18509347

ABSTRACT

Diabetes mellitus often develops in patients with hypertension. We investigated predictors of diabetes mellitus development in hypertensives at risk of developing the disease in the VALUE trial population. Among the 9995 non-diabetic hypertensive patients at baseline, 1298 patients developed diabetes mellitus during the average follow-up of 4.2 years. New-onset diabetes mellitus was defined from adverse event reports, information about new antidiabetic medication and/or a fasting glucose >or=7.0 mmol l(-1) at the end of trial. Twenty-five potential baseline predictors of new-onset diabetes mellitus were analysed by univariate logistic regression and 14 of 25 predictors were found to be statistically significant with a P-value <0.05. The predictors were in order of decreasing significance; glucose, body mass index (BMI), age, uric acid, non-Caucasian race, haemoglobin, heart rate, randomized study treatment, history of coronary heart disease (CHD), gender, total cholesterol, proteinuria, potassium and creatinine. Multivariate stepwise logistic regression analyses were used and potential baseline predictors of new-onset diabetes mellitus were considered significant by four different models (P-value <0.001). The final multivariate model selected included all patients, but not treatment group as a potential predictor, and the six significant predictors identified from this model were glucose, BMI, non-Caucasian race, age, heart rate and history of CHD. In conclusion, glucose and BMI were the most important predictors of new-onset diabetes mellitus in hypertensive patients at high cardiovascular risk, and easily accessible clinical characteristics strongly predict patients at risk of developing diabetes mellitus.


Subject(s)
Amlodipine/therapeutic use , Diabetes Mellitus/etiology , Hypertension/drug therapy , Tetrazoles/therapeutic use , Valine/analogs & derivatives , Angiotensin II Type 1 Receptor Blockers , Antihypertensive Agents/therapeutic use , Blood Glucose/metabolism , Blood Pressure/physiology , Body Weight , Calcium Channel Blockers/therapeutic use , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Double-Blind Method , Drug Therapy, Combination , Follow-Up Studies , Humans , Hypertension/complications , Hypertension/physiopathology , Incidence , Middle Aged , Prognosis , Prospective Studies , Risk Factors , Time Factors , Valine/therapeutic use , Valsartan
19.
Eur J Echocardiogr ; 9(1): 34-9, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17448731

ABSTRACT

AIMS: Hypertension is one of several risk factors of cardiovascular disease and is associated with left ventricular (LV) systolic and diastolic dysfunction. A method for reliably detecting the onset of LV dysfunction before transition to irreversible damage of the myocardium would be of crucial importance in subjects with essential hypertension. METHODS AND RESULTS: Subjects with clear differences in BP level, development and duration of the hypertensive disease were examined at the age of 60 yrs: normotensives (n = 17), new hypertensives who developed hypertension over a 20 year period (n = 15) and hypertensives (n = 19). Relationships between conventional echocardiographic and tissue velocities imaging (TVI) parameters compared to LV parameters, and TVI as an estimate of LV function were explored. E'(Lat) (TVI peak early diastolic velocity) (P = 0.006) and E/E'(Lat) (P = 0.002) demonstrated differences in diastolic function between the groups. There were no significant differences regarding systolic myocardial velocities. E'(Lat) correlated to S'(Lat) (TDI peak systolic velocity) (r = 0.32, P = 0.026) and was independently predicted by S'(Lat) (R(2) = 0.24, P = 0.025) in multivariate analysis. E'(Lat) correlated negatively to LV mass index (r = -0.34, P = 0.012), also in multivariate regression analysis (R(2) = 0.12, P = 0.032). CONCLUSIONS: Myocardial diastolic velocities and mitral flow to annulus velocity ratio differentiated LV function between the hypertensive and normotensive groups. The parameters probably reflect changes in relaxation, recoil and contraction and parallel changes in LV mass index.


Subject(s)
Echocardiography, Doppler , Hypertension/diagnostic imaging , Ventricular Dysfunction, Left/diagnostic imaging , Analysis of Variance , Cross-Sectional Studies , Diastole , Humans , Hypertension/physiopathology , Male , Middle Aged , Predictive Value of Tests , Regression Analysis , Systole , Ventricular Dysfunction, Left/physiopathology
20.
J Hum Hypertens ; 22(1): 63-70, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17728797

ABSTRACT

The prevalence of hypertension continues to rise across the world, and most patients who receive medical intervention are not adequately treated to goal. A Working Group including representatives of nine international health-care organizations was convened to review the barriers to more effective blood pressure control and propose actions to address them. The group concluded that tackling the global challenge of hypertension will require partnerships among multiple constituencies, including patients, health-care professionals, industry, media, health-care educators, health planners and governments. Additionally, health-care professionals will need to act locally with renewed impetus to improve blood pressure goal rates. The Working Group identified five core actions, which should be rigorously implemented by practitioners and targeted by health systems throughout the world: (1) detect and prevent high blood pressure; (2) assess total cardiovascular risk; (3) form an active partnership with the patient; (4) treat hypertension to goal and (5) create a supportive environment. These actions should be pursued with vigour in accordance with current clinical guidelines, with the details of implementation adapted to the economic and cultural setting.


Subject(s)
Global Health , Hypertension/prevention & control , Practice Guidelines as Topic , Delivery of Health Care/standards , Health Planning Guidelines , Humans , Patient Compliance , Risk Assessment
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