Cardiovascular disease healthcare trajectories: descriptions, similarities, mortality rates of heart failure in France.

AIMS: The primary objectives of this study were to analyse the nationwide healthcare trajectories of heart failure (HF) patients in France, 2 years after their first hospitalization, and to measure sequence similarities. Secondary objectives were to identify the association between trajectories and the risk of mortality. METHODS AND RESULTS: A retrospective, observational study was conducted using data extracted from the Echantillon Généraliste des Bénéficiaires database, covering the period from 1 January 2008 to 31 December 2018. Follow-up concluded upon death or at the end of the study. We developed a methodology specific to healthcare data by extracting frequent healthcare trajectories and measuring their similarity for use in a survival machine learning analysis. In total, 11 488 HF patients were included and followed up for an average of 2.9 ± 1.3 years. The mean age of the patients was 78.0 ± 13.2 years. The first-year mortality rate was 31.7% and increased to 78.8% at 5 years. Fifty per cent of patients experienced re-hospitalization for reasons related to cardiovascular diseases. We identified 1707 hospitalization sequences, and 21 sequences were associated with survival, while 15 sequences were linked to mortality. In all our models, age and gender emerged as the most significant predictors of mortality (permutation feature importance: 0.099 ± 0.00078 and 0.0087 ± 0.00018, respectively; weights could be interpreted in relative terms). Specifically, the age at initial hospitalization for HF was positively associated with mortality. Gender (male: 49.5%) was associated with poorer prognoses. Healthcare trajectories, including non-surgical device treatments, valve replacements, and atrial fibrillation ablation, were associated with a better prognosis (permutation feature importance: 0.0047 ± 0.00011, 0.0014 ± 0.000073, and 0.00095 ± 0.000097, respectively), except in cases where these invasive treatments preceded or followed hospitalization for cardiac decompensation. The predominant negative prognosis sequences were mostly those that included HF-related hospitalizations before or after other-related hospitalizations (permutation feature importance: 0.0007 ± 0.000091 and 0.00011 ± 0.000045, respectively). CONCLUSIONS: We highlight the value of healthcare trajectories on frequent hospitalization sequences, mortality, and prognosis and indicate the necessary prognostic value of HF re-hospitalization. Our work may be an essential tool for better identification of at-risk patients in order to increase and improve personalized care in the future.

Coaching of lifestyle recommendations improves sensory neurophysiological parameters in neuropathies related to glycemic disorder or metabolic syndrome. A pilot study.

OBJECTIVES: Metabolic abnormalities, such as, glycemic disorders and metabolic syndrome (GDMS) are one of the main causes of peripheral neuropathies. The objective of this study was to evaluate the impact of adding specific coaching care (CC) to standard care (SC) of therapeutic education based on lifestyle recommendations for neuropathies associated with GDMS. METHODS: This prospective randomized study included two groups of four patients (SC vs. CC) with examiners blinded to group allocation. The SC group had one day of therapeutic education on lifestyle measures (physical activity and diet recommendations) followed by only one phone call of reinforcement. The CC group received an additional weekly phone call of reinforcement for 3 months. Clinical, biological and neurophysiological variables were compared between the two groups at baseline and for the percentage of change at 3 months. RESULTS: All patients (4 men and 4 women) had diabetes or pre-diabetes, which was associated with metabolic syndrome in 5 cases. There was no difference on any variable at baseline, but at 3 months, Mann-Whitney test showed a difference (P=0.0008) between the two groups regarding the sensory neurophysiological variable, which deteriorated in the SC group (median: -6.0%) and improved in the CC group (median: +12.4%). No significant difference was observed between the two groups for the other variables at 3 months. CONCLUSION: The weekly coaching of recommendations for lifestyle measures over a period of three months allows an improvement of GDMS neuropathies, at least in terms of sensory aspects, as evidenced by neurophysiological assessments.

Carotid-femoral pulse wave velocity is not increased in obesity.

BACKGROUND: There are conflicting results in the literature concerning the relationship between obesity and arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV). The discrepancies could be due to differences in carotid-femoral distance measurement and/or to the presence of pathologies frequently associated with obesity and which increase arterial stiffness. In this study, we examine the relationship between PWV and weight, without and with associated cardiovascular risk factors (diabetes and/or dyslipidemia). METHODS: PWV was assessed with a Complior SP device (Alam Medical, France) in 2,034 patients referred for ambulatory blood pressure monitoring. The carotid-femoral distance used to calculate PWV was measured with a flexible tape and from the estimated straight carotid-femoral distance obtained with a published equation. RESULTS: In the whole cohort, PWV did not differ significantly according to weight (9.6±2.1, 9.8±2.2 and 9.7±1.9 m/s in normal weight, overweight and obese subjects, respectively, with the distance measured with a tape). PWV was significantly higher in the four groups of patients with cardiovascular risk factors (e.g., 11.1±2.4, 11.0±2.7 and 10.4±2.0 m/s in normal weight, overweight, and obese subjects, respectively, in the group treated for diabetes and dyslipidemia) than in the group of patients without cardiovascular risk factors (8.5±1.6, 8.8±1.7 and 8.5±1.2 in normal weight, overweight, and obese subjects, respectively). There was no relationship between PWV value and weight status, whether or not there were cardiovascular risk factors, and whatever the distance used to calculate PWV. CONCLUSIONS: In our cohort, obesity per se was not associated with increased arterial stiffness.

Antihypertensive drug classes have different effects on short-term blood pressure variability in essential hypertension.

Increased blood pressure variability (BPV) contributes to end-organ damage, cardiovascular events and mortality associated with hypertension. In a cohort of 2780 hypertensive patients treated by either calcium channel blockers (CCBs), diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) or ß-blockers alone or in combination, we compared indices of short-term BPV according to the different treatments. Short-term BPV was calculated as the standard deviation (s.d.) of 24 h, daytime or nighttime systolic blood pressure and diastolic blood pressure (SBP and DBP). Short-term BPV was compared between patients treated with a given antihypertensive class of interest (alone or in combination) and those not treated with this class, after controlling for ambulatory average blood pressure, heart rate, age, gender, propensity scores and carotid-femoral pulse wave velocity. Patients treated with CCBs (n=1247) or diuretics (n=1486) alone, or in addition to other drugs had significant lower s.d. of 24-h SBP compared with those not treated with these classes (mean differences in s.d. -0.50±0.50 mm Hg, P=0.001 and -0.17±0.15 mm Hg, P=0.05, respectively). There was no significant difference regarding treatment with or without ARBs, ACEIs and ß-blockers. The combinations of CCBs with diuretics or ARBs on top of other treatments resulted in a lower 24-h SBP variability (mean differences in s.d. -0.43±0.17 mm Hg, P=0.02 and -0.44±0.19 mm Hg, P=0.005 vs. other combination uses, respectively). Antihypertensive drug classes have differential effects on short-term BPV with a greater reduction in patients treated with CCBs and diuretics. The combinations of CCBs with diuretics may be the most efficient treatments in lowering BPV.

Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis.

OBJECTIVES: Prevention of cognitive decline and dementia with blood pressure lowering treatments has shown inconsistent results. We compared the effects of different classes of antihypertensive drugs on the incidence of dementia, and on cognitive function. METHODS: We conducted a systematic review and included 19 randomized trials (18 515 individuals) and 11 studies (831 674 individuals) analysing the effects of antihypertensive treatment on cognition and on the incidence of dementia, respectively, in hypertensive patients without prior cerebrovascular disorders. Network meta-analysis was used for the comparison of antihypertensive classes. RESULTS: Antihypertensive treatment, regardless of the drug class, had benefits on overall cognition [effect size 0.05, 95% confidence interval (CI) 0.02-0.07] and all cognitive functions except language. Antihypertensive treatment reduced the risk of all-cause dementia by 9%, with reference to the control group (hazard ratio 0.91, 95% CI 0.89-0.94), when randomized trials and observationnal studies were combined (n = 15). Result was not significant with randomized trials alone (n = 4). Angiotensin II receptor blockers (ARBs) had larger benefits than placebo on overall cognition (adjusted effect size 0.60 ±â€Š0.18, P = 0.02). ARBs were more effective than ß-blockers (0.67 ±â€Š0.18, P = 0.01), diuretics (0.54 ±â€Š0.19, P = 0.04) and angiotensin-converting enzyme inhibitors (0.47 ±â€Š0.17, P = 0.04) in rank. The mean change in blood pressure did not differ significantly between the different antihypertensive drug classes. CONCLUSION: Our results support the notion that antihypertensive treatment has beneficial effects on cognitive decline and prevention of dementia, and indicate that these effects may differ between drug classes with ARBs possibly being the most effective.

Crucial importance of using a sliding calliper to measure distance for carotid-femoral pulse wave velocity assessment.

BACKGROUND AND OBJECTIVES: In the past, different methods have been used to measure the carotid-femoral distance for the assessment of pulse wave velocity (PWV). However, the latest consensus published advises to use 80% of the direct straight carotid-femoral distance (D(0.8)) using either a flexible tape or a sliding calliper. We studied the influence of the use of a tape measure and a calliper on PWV values and provided equations to derive the straight D(0.8) distance from previous methodologies. METHODS: PWV was measured in patients referred for ambulatory blood pressure monitoring. Carotid-femoral, carotid-sternal notch, and sternal notch-femoral distances were measured with a tape and a sliding calliper. RESULTS: Two hundred and fifty-nine patients (141 men and 118 women) were recruited consecutively. Their BMI ranged from 18 to 45 kg/m(2) (28.4 ±â€Š5.0, mean ±â€ŠSD). As expected, distances measured with tape were longer (3.1 ±â€Š1.3 cm for D(0.8)) leading to higher values of PWV (0.6 ±â€Š0.3 m/s for PWV(0.8)). This difference was similar in men and women and depended for 20% on the BMI. Equations explaining more than 85% of variance can be used to convert tape carotid-femoral, carotid-sternal notch, and tape sternal notch-femoral distances to D(0.8). CONCLUSION: It is crucial to use a sliding calliper to assess distances for PWV measurement. The overestimation with flexible tape depends on the BMI but not on the sex. Conversion equations between previous methods and the D(0.8) method can be used.

Target organ damage assessment in French hypertensive patients without established cardiovascular or renal disease: results of the PREVENT-A study.

OBJECTIVES: To evaluate the modalities of subclinical target organ damage (TOD) assessment in France, 2-3 years after publication of the European Society of Hypertension (ESH)/European Society of Cardiology (ESC) 2007 guidelines. METHODS: Two parallel, large, cross-sectional surveys were performed in representative samples of 516 private practice cardiologists, and 943 general practitioners (GPs), in hypertensive patients (952 and 1778, respectively) without established cardiovascular or renal disease. RESULTS: At least one TOD search was performed in 97.6% of cardiologists' patients, performed or ongoing in 96.1% of GPs' patients, with a median number of three TOD searches in both surveys. Only 8.6% of cardiologists' patients and 6.3% of GPs' patients had a full set of TOD analyses [i.e. the five categories investigated: left ventricular hypertrophy (LVH), vascular, renal, retinopathy and cerebrovascular]. When considering the three priority categories of subclinical TOD search recommended by the ESH/ESC guidelines (i.e. LVH, vascular and renal), 63.2% of cardiologists' patients and 49.5% of GPs' patients had this triple assessment completed. The new TOD assessment modalities, namely pulse wave velocity, ankle brachial index and microalbuminuria, were rarely used. Only 3.3% of GPs' patients and 15.4% of cardiologists' patients were reclassified with an upgraded cardiovascular risk. CONCLUSION: Subclinical TOD modalities are commonly assessed in French hypertensive patients without established cardiovascular or renal diseases, although 55% still do not benefit from combined triple LVH, macrovascular and renal assessment. The new modalities of TOD assessment are rarely implemented. Moreover, TOD assessment displayed poor effectiveness in upgrading cardiovascular risk classification.

Do all antihypertensive drugs improve carotid intima-media thickness? A network meta-analysis of randomized controlled trials.

The many clinical trials investigating the effect of various antihypertensive drugs on carotid intima-media thickness (CIMT) produced conflicting results. We used meta-analysis to evaluate CIMT changes and network meta-analysis to rank drugs according to the magnitude of these changes. We identified 31 randomized controlled trials listed in three databases as of January 2008. Using a random-effects model, we found a significant CIMT decrease with antihypertensive drugs compared to placebo (-0.10 [-0.16; -0.04]). Overall effect sizes vs. placebo were significant for angiotensin-converting enzyme (ACE) inhibitors (-0.08 [-0.14; -0.02]), and a trend was found for beta-blockers (-0.09 [-0.19; 0.01]). The data did not allow other direct comparisons vs. placebo. Significant benefits were found for calcium-channel blockers (CCBs) compared to both ACE inhibitors (0.37 [0.20; 0.54]), as well as for angiotensin II receptor blockers (ARBs) compared to beta-blockers (0.42 [0.29; 0.55]). Diuretics were less efficient than CCBs (-0.09 [-0.16; -0.02]). Indirect comparisons with network meta-analysis showed significant effects of CCBs and ARBs vs. placebo (both P < 0.05) and vs. diuretics (both P < 0.001). The CIMT decrease with ACE inhibitors and beta-blockers was greater than with diuretics (both P < 0.05) but was not different from the placebo effect. In subgroup analyses, significant benefits occurred with lower baseline CIMT values and shorter treatment durations but were unrelated to the size of the blood pressure decrease. In conclusion, among antihypertensive drugs, CCBs and ARBs have the greatest effect on CIMT.

Lowering of brachial pulse pressure in 9379 hypertensives with type 2 diabetes and reduction of cardiovascular events.

OBJECTIVES: Pulse pressure (PP) is a major risk factor for cardiovascular (CV) events, mainly in diabetic hypertensives. The objectives of the study were to determine which clinical characteristics could predict the fall in PP and the reduction of CV events under treatment. Design and methods. Type 2 diabetic hypertensives (n = 9379) with PP>60 mmHg (mean age 64 years) were included in a cohort study. During the 9 months follow-up, the physician in charge was asked to reinforce treatment in order to lower PP, using preferentially a fixed low-dose perindopril/indapamide combination. RESULTS: After 9 months, PP had fallen by 9.1+/-0.2 mmHg (p<0.001). Multivariate analysis of the determinants of PP reduction showed a significant positive association with administration of fixed ACEI/diuretic combination (p<0.001) and a negative association with glycated hemoglobin (p<0.01). During the 9 months follow-up, 632 CV events occurred. In multivariate analysis, the administration of fixed perindopril/indapamide combination was associated with a lower incidence of CV events (OR = 0.64 [0.48-0.86], p<0.01), independently of CV risk factors. CONCLUSIONS: The reinforcement of therapeutic measures made possible the reduction of PP in type 2 diabetic hypertensives, under conditions of usual care. Administration of a fixed perindopril/indapamide combination therapy was associated with an independent reduction of CV events.

Impact of somatostatin analogs on the heart in acromegaly: a metaanalysis.

CONTEXT: Acromegaly can be complicated by cardiomyopathy. Treatment with somatostatin analogs has been shown to improve some cardiac parameters, but most published clinical trials involved few patients and were not randomized or controlled. In addition, their results are rather variable. OBJECTIVE: The objective of the study was to conduct a metaanalysis aimed at obtaining a more accurate picture of the effect of somatostatin analogs on the heart in patients with acromegaly. DESIGN: We systematically reviewed all studies of somatostatin analogs in acromegaly. Eighteen studies were identified in three databases. We conducted a combined analysis of the effects of somatostatin analogs by using the overall effect size to evaluate significance and by computing the weighted mean differences with and without treatment to assess the effect size. RESULTS: Somatostatin analog treatment was associated with significant reductions in the heart rate [-5.8 (2.1) beats/min], the left ventricular mass index [-22.3 (6.7) g/m(2)], interventricular septum thickness [-0.3 (0.2) mm], left ventricular posterior wall thickness [-0.8 (0.4) mm], and the ratio of the E-wave and A-wave peak velocities of the mitral flow profile [0.2 (0.1)]. It was also associated with improved exercise tolerance [1.6 (0.4) min]. Trends toward beneficial effects were noted for the left ventricular end-diastolic dimension [-1.5 (2.2) mm] and the left ventricular ejection fraction [3.3% (1.7%)]. Overall effect sizes were not significant for blood pressure, left ventricular end-systolic dimension, or fractional shortening. Bigger improvements were observed in studies with larger falls in IGF-I and/or GH levels and studies of younger patients. CONCLUSION: This metaanalysis confirms that somatostatin analog therapy aimed at achieving stringent control of serum GH/IGF-I concentrations in patients with acromegaly is associated with significant positive effects on morphological and functional hemodynamic parameters.

Different effects of ambulatory blood pressure monitoring on subjective and objective sleep quality.

OBJECTIVE: To determine whether ambulatory blood pressure monitoring affects objective and subjective sleep quality in patients tested at home. METHODS: Seventy consecutive patients (40 women and 30 men, aged 53+/-15 years), having ambulatory blood pressure monitoring to monitor the efficacy of antihypertensive treatment or to distinguish between hypertension or white-coat hypertension had an evaluation of their sleep quality on a first night with ambulatory blood pressure monitoring and the three following nights without ambulatory blood pressure monitoring. Ambulatory blood pressure monitoring was performed with an auscultatory device with a measure every 15 min during 24 h. Sleep evaluation criteria were both subjective (sleep quality score and sleep questionnaire) and objective (wrist actigraphy monitoring). Sleep parameters during night 1 with ambulatory blood pressure monitoring were compared with those during night 4 without ambulatory blood pressure monitoring. Usual quality of sleep of the patients was assessed by the mean sleep quality score over 7 consecutive days. RESULTS: The sleep quality score was significantly higher for night 4 than for night 1 (7.3+/-2.1 vs. 5.3+/-2.3; P<0.0001). In contrast, actigraphy parameters (actual sleep time, mean activity score, and fragmentation index) were similar on night 1 and night 4 (6.7+/-1.2 vs. 6.9+/-1.2, 13.2+/-9.8 vs. 12.1+/-8.4, and 31.0+/-14.5 vs. 29.9+/-14.3, respectively). Subjective sleep quality was significantly altered by ambulatory blood pressure monitoring in good sleepers (mean sleep quality score > or =7, 73% of patients) but not in poor sleepers. The effect of ambulatory blood pressure monitoring on subjective sleep quality did not differ between dippers and nondippers. CONCLUSIONS: Objective sleep quality as assessed by wrist actigraphy is not significantly altered by ambulatory blood pressure monitoring, whereas subjective sleep quality is adversely affected in good sleepers.

Brachial pressure-independent reduction in carotid stiffness after long-term angiotensin-converting enzyme inhibition in diabetic hypertensives.

Hypertension and diabetes are associated with an increased arterial stiffness. A direct blood pressure-independent effect of angiotensin-converting enzyme inhibitors on arterial stiffness has never been unequivocally demonstrated. In this mechanistic study, we used an experimental design in which patients responding to 1 month treatment with 4 mg perindopril were randomized double-blind to either 4 mg perindopril or 8 mg perindopril for 6 months. We determined carotid distensibility with echotracking and applanation tonometry at baseline and after the 7-month treatment period in 57 essential hypertensive patients with type 2 diabetes (age 63+/-7 years). We monitored ambulatory blood pressure at baseline and after treatment. After 7 months treatment, 24-hour ambulatory blood pressure significantly decreased, with no significant difference between 4 mg and 8 mg perindopril. Carotid distensibility increased more after 8 mg perindopril compared with 4 mg perindopril (8 mg: from 13.1+/-5.9 to 16.0+/-6.7 kPa(-1)x10(-3); 4 mg: from 13.2+/-5.2 to 12.7+/-5.9 kPa(-1)x10(-3); ANOVA, dose-period interaction, P<0.05). Carotid internal diameter and elastic modulus were significantly lower after 8 mg perindopril compared with 4 mg perindopril, independent of blood pressure reduction. These results indicate a dose-dependent and blood pressure-independent reduction in carotid stiffness under chronic treatment with an angiotensin-converting enzyme inhibitor. They suggest that arterial distensibility was increased through an inward remodeling, leading to a reduction in wall stress, thus reducing elastic modulus. They also suggest that long-term administration of high doses (8 mg) of perindopril is required to improve carotid structure and function in hypertensive patients with type 2 diabetes.

Pulse pressure reduction and cardiovascular protection.

Brachial pulse pressure (PP) is now a well-established cardiovascular risk factor. Central rather than peripheral PP should be measured to determine the 'true' haemodynamic effects of antihypertensive agents on target organs. Peripheral PP, measured at the brachial artery, does not reflect central PP (either carotid or ascending aorta), because their determinants are different and pathophysiological conditions and drugs may change central PP without changing peripheral PP. Central PP (i.e. carotid artery or ascending aorta) has shown an independent predictive value for all-cause mortality in patients with end-stage renal disease and in the hypertensive patients of the CAFE study. Antihypertensive treatment has repeatedly demonstrated its ability to prevent cardiovascular events. Whether the effect on cardiovascular events in clinical trials comparing two pharmacological classes or two therapeutic strategies is, at least partly, the result of differential effects on PP remains to be demonstrated. It is therefore of major importance to determine which therapeutic strategies may differentially lower central PP, and in turn reduce cardiovascular events. In clinical practice, lowering PP is often a difficult task, particularly in diabetic hypertensive individuals. In the PARADIS study, we aimed to determine, in a population of hypertensive patients with both type 2 diabetes and PP greater than 60 mmHg, which clinical characteristics predict the fall in PP on treatment and a reduction in cardiovascular events. The reinforcement of therapeutic measures, including a fixed low-dose perindopril/indapamide combination, made possible the effective lowering of PP and cardiovascular events in type 2 diabetic hypertensive patients, under conditions of usual care by general practitioners and specialists.

Carotid and aortic stiffness: determinants of discrepancies.

Several studies have shown that aortic stiffness was an independent predictor for cardiovascular events. However, data are less consistent concerning carotid stiffness. We analyzed the determinants of the discrepancies between aortic and carotid stiffness in different populations with contrasting cardiovascular risk factors: 94 healthy normotensives (NT), 243 nondiabetic hypertensives (HT), and 126 patients with hypertension and type 2 diabetes (T2D). Aortic stiffness was measured with carotid-femoral pulse wave velocity. Common carotid stiffness was determined from the relative stroke change in diameter (measured with a high-resolution echotracking system) and carotid pulse pressure (measured with applanation tonometry) and was expressed in the same dimensions as pulse wave velocity (m/s). We identified the various factors explaining the discrepancies between aortic and carotid stiffness by multivariate analysis of the residuals of the correlation between aortic and carotid stiffness. The strength of the correlation between aortic and carotid stiffness became weaker as the number of cardiovascular risk factors increased (NT, r2=0.41; HT, r2=0.16; and T2D, r2=0.11), whereas we observed the opposite for the discrepancies (residuals) between aortic and carotid stiffness, of which an increasing part was explained (11% in NT, 22% in HT, and 45% in T2D) primarily by aging. In conclusion, although carotid-femoral pulse wave velocity and carotid stiffness provided similar information on the impact of aging on large artery stiffness in normal subjects, this was not the case for high blood pressure and/or diabetes. In these cases, the aorta stiffened more than the carotid artery with age and other cardiovascular risk factors.

Glucose level is a major determinant of carotid intima-media thickness in patients with hypertension and hyperglycemia.

BACKGROUND: A causal relationship has been established between hyperglycemia and cardiovascular diseases, but no threshold has been retained to determine a 'glycemia-associated' cardiovascular risk. Carotid intima-media thickness (CIMT) is an independent predictor for cardiovascular events. High blood pressure is a major determinant of CIMT. OBJECTIVES: To determine the influence of fasting glycemia on CIMT in hypertensive patients with either normal fasting glucose, impaired fasting glucose (IFG) or type 2 diabetes (DM-2). METHODS: We included 158 essential hypertensive patients with either normal fasting glucose (n=74), IFG (n=24) or DM-2 (n=60) in a cross-sectional study. Common carotid IMT was measured with a high resolution echotracking system. RESULTS: CIMT of DM-2 patients was significantly higher than that of IFG and normal fasting glucose patients (809 +/- 180, 697 +/- 151 and 689 +/- 134 microm, respectively; analysis of variance (ANOVA) P <0.0001). In multivariate analysis in normal fasting glucose patients, local pulse pressure and age were the major determinants of CIMT, whereas glycemia was not. In IFG and DM-2 patients, fasting glycemia was strongly associated with CIMT, explaining 21 and 18% of its variance, respectively. Particularly, in IFG patients, an increase in 1 mmol/l glycemia was associated with a 165 microm increase in CIMT. In hyperglycemic patients, with either IFG or DM-2, age was an important determinant of CIMT, whereas local pulse pressure was not. CONCLUSION: These data suggest that glycemia is a major independent determinant of CIMT in hypertensive hyperglycemic patients, not only in DM-2 patients but also at the earlier stage of IFG, offsetting the mechanical role of local pulse pressure.

Angiotensinogen gene M235T polymorphism and reduction in wall thickness in response to antihypertensive treatment.

The angiotensinogen M235T polymorphism has been linked to hypertension and cardiovascular disease. Carotid intima-media thickness (IMT) is an early marker of atherosclerosis. The objectives of the present study were to determine in previously untreated essential hypertensive patients whether carotid IMT was associated with the M235T polymorphism, and to determine whether the M235T polymorphism could influence the reduction of carotid IMT by antihypertensive treatment. Common carotid artery IMT was determined with a high-definition echotracking system in 98 previously untreated hypertensive patients in a cross-sectional study. A subgroup of 56 patients was included in a randomized double-blind parallel group study comparing the effect of the angiotensin-converting-enzyme-inhibitor enalapril with that of the beta-blocker celiprolol during a 5 month period. In the cross-sectional study, a multivariate analysis showed that the M235T genotype was a significant independent determinant of carotid IMT, explaining 7% of the variance. Carotid IMT was higher in patients homozygous for the T allele than in MM patients. In the longitudinal study, the reduction in carotid IMT after antihypertensive treatment was significantly ( P <0.01) higher in patients carrying the TT genotype than in patients carrying the MM genotype, despite similar reductions in blood pressure and independently of drug type. In conclusion, these data suggest that the angiotensinogen TT genotype at position 235 is a genetic marker for early carotid atherosclerosis in a hypertensive population and its regression under antihypertensive treatment.

Aortic stiffness is an independent predictor of fatal stroke in essential hypertension.

BACKGROUND AND PURPOSE: Pulse pressure is a stronger predictor of cardiovascular events than systolic or diastolic blood pressure in large cohorts of French and North American patients. However, its influence on stroke is controversial. Large-artery stiffness is the main determinant of pulse pressure. The influence of arterial stiffness on the occurrence of stroke has never been demonstrated. Our aim was to establish the relationship between aortic stiffness and stroke death in hypertensive patients. METHODS: We included, in a longitudinal study, 1715 essential hypertensive patients who had a measurement of arterial stiffness at entry (ie, between 1980 and 2001) and no overt cardiovascular disease or symptoms. Mean follow-up was 7.9 years. At entry, aortic stiffness was assessed from the carotid-femoral pulse wave velocity. A Cox proportional hazard regression model was used to estimate the relative risk (RR) of stroke and coronary deaths. RESULTS: Mean+/-SD age at entry was 51+/-13 years. Twenty-five fatal strokes and 35 fatal coronary events occurred. Pulse wave velocity significantly predicted the occurrence of stroke death in the whole population. There was a RR increase of 1.72 (95% CI, 1.48 to 1.96; P<0.0001) for each SD increase in pulse wave velocity (4 m/s). The predictive value of pulse wave velocity remained significant (RR=1.39 [95% CI, 1.08 to 1.72]; P=0.02) after full adjustment for classic cardiovascular risk factors, including age, cholesterol, diabetes, smoking, mean blood pressure, and pulse pressure. In this population, pulse pressure significantly predicted stroke in univariate analysis, with a RR increase of 1.33 (95% CI, 1.16 to 1.51) for each 10 mm Hg of pulse pressure (P<0.0001) but not after adjustment for age (RR=1.19 [95% CI, 0.96 to 1.47]; P=0.10). CONCLUSIONS: This study provides the first evidence, in a longitudinal study, that aortic stiffness is an independent predictor of fatal stroke in patients with essential hypertension.

Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study.

Arterial stiffness may predict coronary heart disease beyond classic risk factors. In a longitudinal study, we assessed the predictive value of arterial stiffness on coronary heart disease in patients with essential hypertension and without known clinical cardiovascular disease. Aortic stiffness was determined from carotid-femoral pulse wave velocity at baseline in 1045 hypertensives. The risk assessment of coronary heart disease was made by calculating the Framingham risk score according to the categories of gender, age, blood pressure, cholesterol, diabetes, and smoking. Mean age at entry was 51 years, and mean follow-up was 5.7 years. Coronary events (fatal and nonfatal myocardial infarction, coronary revascularization, and angina pectoris) and all cardiovascular events served as outcome variables in Cox proportional-hazard regression models. Fifty-three coronary events and 97 total cardiovascular events occurred. In univariate analysis, the relative risk of follow-up coronary event or any cardiovascular event increased with increasing level of pulse wave velocity; for 1 SD, ie, 3.5 m/s, relatives risks were 1.42 (95% confidence interval [CI], 1.10 to 1.82; P<0.01) and 1.41 (95% CI, 1.17 to 1.70; P<0.001), respectively. Framingham score significantly predicted the occurrence of coronary and all cardiovascular events in this population (P<0.01 and P<0.0001, respectively). In multivariate analysis, pulse wave velocity remained significantly associated with the occurrence of coronary event after adjustment either of Framingham score (for 3.5 m/s: relative risk, 1.34; 95% CI, 1.01 to 1.79; P=0.039) or classic risk factors (for 3.5 m/s: relative risk, 1.39; 95% CI, 1.08 to 1.79; P=0.01). Parallel results were observed for all cardiovascular events. This study provides the first direct evidence in a longitudinal study that aortic stiffness is an independent predictor of primary coronary events in patients with essential hypertension.