Thromboembolic risk after lumbar spine surgery: a cohort study on 325 000 French patients.

Essentials The risk of venous thromboembolism (VTE) after lumbar spine surgery (LBS) is not precisely known. More than 320 000 patients who underwent LBS in France between 2009 and 2014 were followed-up. The overall risk of VTE after LBS is less than 1% but modulated by patient and procedural factors. Surgical device implantation, anterior approach and complex surgery increase the risk of VTE. SUMMARY: Background Postoperative venous thromboembolism (VTE) is a severe complication, the risk of which after lumbar spine surgery (LBS) is not precisely known. Objective To estimate the incidence of VTE after LBS, and to identify individual and surgical risk factors. Methods All patients aged >18 years who underwent LBS in France between 2009 and 2014 were identified. Among 477 024 patients screened, exclusions concerned recent VTE or surgery, and multiple surgeries during the same hospital stay. Results In 323 737 patients (mean age 52.9 years, 51.4% male), we observed 2911 events (0.91%) after a median time of 12 days (Q1-Q3: 5-72 days). The multivariate adjusted Cox model showed increased risks associated with age (4% per year of age; 95% confidence interval [CI] 3.8-4.3), obesity (hazard ratio [HR] 1.32, 95% CI 1.18-1.46), active cancer (HR 1.65, 95% CI 1.5-1.82), previous thromboembolism (HR 5.41, 95% CI 4.74-6.17), severe paralysis (HR 1.47, 95% CI 1.17-1.84), renal disease (HR 1.28, 95% CI 1.04-1.6), psychiatric disease (HR 1.21, 95% CI 1.1-1.32), use of antidepressants (HR 1.13, 95% CI 1.03-1.24), use of contraceptives (HR 1.56, 95% CI 1.19-2.03), extended surgery for scoliosis (HR 3.61, 95% CI 2.96-4.4), implantation of pedicular screws with a 'dose-effect' association, and an anterior approach (HR 1.97, 95% CI 1.6-2.43) or a combined approach (HR 2.03, 95% CI 1.44-2.84). Conclusions The overall VTE risk after LBS is moderate (< 1%) but is widely modulated by several easily identifiable risk factors. The surgical community should be aware of this heterogeneity, adapt prevention according to patients and to the procedure, and use drug prophylaxis in the event of a high risk being present.

Therapeutic management of inflammatory bowel disease in real-life practice in the current era of anti-TNF agents: analysis of the French administrative health databases 2009-2014.

BACKGROUND: Management of inflammatory bowel disease (IBD) has evolved in the last decade. AIM: To assess IBD therapeutic management, including treatment withdrawal and early treatment use in the current era of anti-TNF agents (anti-TNFs). METHODS: All patients affiliated to the French national health insurance diagnosed with IBD were included from 2009 to 2013 and followed up until 31 December 2014. Medication uses, treatment sequences after introduction of thiopurine or anti-TNF monotherapies or both (combination therapy), surgical procedures and hospitalisations were assessed. RESULTS: A total of 210 001 patients were diagnosed with IBD [Crohn's disease (CD), 100 112; ulcerative colitis (UC), 109 889]. Five years after diagnosis, cumulative probabilities of anti-TNF monotherapy and combination therapy exposures were 33.8% and 18.3% in CD patients and 12.9% and 7.4% in UC patients, respectively. Among incident patients who received thiopurines or anti-TNFs, the first treatment was thiopurine in 69.1% of CD and 78.2% of UC patients. Among patients treated with anti-TNFs, 45.2% and 54.5% of CD patients and 38.2% and 39.9% of UC patients started monotherapy and combination therapy within 3 months after diagnosis, respectively; 31.3% of CD and 27.1% of UC incident patients withdrew from thiopurine or anti-TNFs for more than 3 months after their first course of treatment. Five years after diagnosis, the cumulative risks of first intestinal resection in CD patients and colectomy in UC patients were 11.9% and 5.7%, respectively. CONCLUSIONS: Step-up approach remains the predominant strategy, while exposure to anti-TNFs is high. Surgery rates are low. Treatment withdrawal in IBD is more common than expected.

The impact of cardiovascular profile on persistence associated with antihypertensive medications.

BACKGROUND: Antihypertensive drug treatment (AHT) is effective in reducing the risks of cardiovascular events, but long-term persistence is required to achieve these benefits. The aim of the present study was to evaluate persistence with antihypertensive treatment in France. METHODS AND RESULTS: A total of 6924 patients, first prescribed for hypertension in 2008, were retrospectively studied from the principal French National Public Health Insurance Scheme database. Persistence was defined as remaining on therapy at the end of the 12 months postindex date. Cox proportional hazards regression models controlled for demographics and cardiovascular profile. Over 1 year, 65% of patients were persistent and 16% maintained the initial therapy. When correcting for significant factors determining persistence, a 13% risk reduction of discontinuation is observed with angiotensin II antagonists (AIIAs) and 11% with angiotensin-converting enzymes inhibitors (ACE) compared with thiazide diuretics. Persistence therapy depended significantly on the cardiovascular profile. In the secondary prevention subgroup (18% of the study population), no statistically significant differences were observed between thiazide diuretics and the four major classes. In contrast, a 19% risk reduction of discontinuation is observed with AIIA and with ACE compared with thiazide diuretics for primary prevention patients without diabetes or hyperlipidaemia. CONCLUSIONS: When choosing AHT agents for patients with essential hypertension, practitioners are primarily driven by the cardiovascular profile of patients. The study suggests that the therapeutic decision must encompass the individual 'persistence risk', the latter not being independent from the cardiovascular risk.

Aortic pulse pressure and atherosclerotic structural alterations of coronary arteries.

Pulse pressure (PP) is an independent predictor of myocardial infarction, mainly above 50 years of age. In subjects with preserved ejection fraction (EF), aortic PP predicts the severity of coronary atherosclerosis. Comparable findings in subjects with reduced EF have not been evaluated. In 1337 subjects with severe coronary ischaemic disease, intra-aortic and brachial blood pressures were measured together with EF and coronary angiography to evaluate cardiac function, the presence of coronary stenosis and/or occlusions or calcifications. The presence (odds ratio+/-95% CI) of coronary calcification was marginally but not significantly associated (P=0.06) to increased aortic PP (1.32 (0.97-1.80)), whereas that of coronary occlusion was significantly associated (P<0.01) with decreased aortic PP (0.62 (0.42-0.91)), even after adjustment to EF and heart rate. Increased aortic PP did not correlate with stenosis number. No comparable predictive value was observed using intra-aortic or non-invasive brachial systolic blood pressure (SBP) or diastolic blood pressure (DBP). In high cardiovascular risk populations, even in the presence of reduced EF and high heart rate, intra-aortic PP, but not SBP or DBP, is a significant predictor of coronary occlusions and possibly calcifications, but not stenosis.

Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study.

As statins may contribute to plaque stabilisation, it is important to evaluate whether these drugs may modify arterial stiffness. In 23 patients, aged 32-70 years, with hypertension and hypercholesterolaemia, a double-blind randomised study vs placebo was performed to evaluate whether atorvastatin was able to modify aortic stiffness, measured from aortic pulse wave velocity (PWV), after a 12-week treatment. The results revealed that atorvastatin did not change blood pressure, significantly lowered (P<0.003; <0.002) plasma total and LDL cholesterol, and increased aortic PWV by +8% (vs -2% under placebo) (P

Aortic pulse wave velocity predicts cardiovascular mortality in subjects >70 years of age.

Aortic pulse wave velocity (PWV) is a significant and independent predictor of cardiovascular mortality in subjects with essential hypertension and in patients with end-stage renal disease. Its contribution to cardiovascular risk in subjects 70 to 100 years old has never been tested. A cohort of 141 subjects (mean+/-SD age, 87.1+/-6.6 years) was studied in 3 geriatrics departments in a Paris suburb. Together with sphygmomanometric blood pressure measurements, aortic PWV was measured with a validated automatic device. During the 30-month follow-up, 56 patients died (27 from cardiovascular events). Logistic regressions indicated that age (P=0.005) and a loss of autonomy (P=0.01) were the best predictors of overall mortality. For cardiovascular mortality, aortic PWV was the major risk predictor (P=0.016). The odds ratio was 1.19 (95% confidence interval, 1.03 to 1.37). Antihypertensive drug treatment and blood pressure, including systolic and pulse pressure, had no additive role. In subjects 70 to 100 years old, aortic PWV is a strong, independent predictor of cardiovascular death, whereas systolic or pulse pressure was not. This prospective result will need to be confirmed in an intervention trial.

Aortic pulse wave velocity as a marker of cardiovascular disease in subjects over 70 years old.

BACKGROUND: Aortic pulse wave velocity (PWV) is a significant and independent predictor of cardiovascular diseases (CVD) in hypertensive subjects and in patients with end-stage renal disease, but its contribution to cardiovascular risk in subjects between 70 and 100 years old has never been tested. PATIENTS: A cohort of 124 subjects (mean age: 87 +/- 7 years) was studied in two geriatric departments in a Paris suburb. Together with sphygmomanometric blood pressure measurements, aortic PWV was measured using a validated automatic device. RESULTS: Blood pressure, heart rate and body mass index, but not age, explained 48% of the PWV variability in this cohort. Furthermore, PWV was the major factor predicting the presence of CVD. The adjusted odds ratio was 17.44 (95% confidence intervals: 2.52-120.55). Antihypertensive drug therapy and low plasma albumin level had only an additive role. Blood pressure, particularly pulse pressure, had no predictive value. CONCLUSION: In 70-100-year-old subjects, aortic PWV is a strong independent marker of CVD, a finding that remains to be to confirmed by long-term longitudinal studies.

Cardiovascular mortality in hypertensive men according to presence of associated risk factors.

To evaluate the risk of cardiovascular disease (CVD) mortality in hypertensive men according to the presence of associated risk factors (ARFs). The population was composed of 29 640 normotensive men without ARFs (reference group) and 60 343 hypertensive men (with and without ARFs) who had a standard health checkup at the Centre d'Investigations Préventives et Cliniques between 1978 and 1988. Mortality data for a mean period of 14 years were analyzed. The following ARFs were considered: total cholesterol >/=2.5 g/L, personal history of diabetes, smoking (current smokers), body mass index >28 kg/m(2), and heart rate >80 bpm. CVD risk related to the presence of isolated hypertension (assessed in hypertensive subjects without ARFs versus the reference group) increased linearly from 15% at the age of 30 years to 134% at the age of 80 years. In hypertensive subjects, one additional ARF increased CVD risk by 56% (47% to 65%, P<0.01) in younger subjects but only by 4% (-8% to 17%, P=NS) in older subjects. The role of hypercholesterolemia and tobacco smoking in CVD mortality was significantly higher in hypertensive subjects aged <55 years than in hypertensive subjects aged >/=55 years (P<0.01), whereas the roles of tachycardia and obesity were not affected by age. In younger hypertensive subjects, evaluation of CVD risk and therapeutic strategies should target ARFS: In older subjects, the presence of high blood pressure levels seems to be the major determinant of CVD risk.

Creatinine clearance, pulse wave velocity, carotid compliance and essential hypertension.

BACKGROUND: The vascular hallmark of subjects with end-stage renal disease is increased arterial stiffness independent of blood pressure, wall stress, and cardiovascular risk factors such as hypertension, plasma glucose and cholesterol, obesity, and tobacco consumption. Whether arterial stiffness and kidney function are statistically associated in subjects with plasma creatinine < or =130 micromol/L has not yet been determined. Material. In 1290 subjects with normal or elevated blood pressure values and plasma creatinine < or =130 micromol/L, subjects were divided into three tertiles according to the calculated creatinine clearance. Blood pressure, aortic pulse wave velocity (PWV), and standard cardiovascular risk factors were determined in parallel. In 112 of the hypertensive subjects, common carotid and radial artery structure and function (high-resolution echo-Doppler techniques) also were measured. RESULTS: From the 1290 subjects, only the low-tertile group presented a significant negative association between PWV and creatinine clearance independently of blood pressure and standard risk factors. This association was stronger in subjects < or =55 years of age. In the 112 hypertensive subjects, carotid compliance was positively correlated to creatinine clearance even after an adjustment for age, gender, and blood pressure. At less than 55 years of age, creatinine clearance represented 20% of the variance of carotid compliance. Such findings were not observed for radial artery compliance. CONCLUSION: Increased stiffness of central arteries is statistically associated with reduced creatinine clearance in subjects with mild-to-moderate renal insufficiency, indicating that kidney alterations may interact not only with small but also large arteries, and this is independent of age, blood pressure, and standard risk factors.

Pulse pressure and aortic pulse wave are markers of cardiovascular risk in hypertensive populations.

BACKGROUND: Pulse pressure (PP) and aortic pulse wave velocity (PWV) are significant markers of cardiovascular risk, but a similar role for central wave reflections has never been investigated. PROCEDURES: To determine the factors influencing PP, PWV, and carotid wave reflections, a cohort of 1087 patients with essential hypertension either treated or untreated was studied cross-sectionally. Atherosclerotic alterations (AA) were defined on the basis of clinical events and PWV evaluated from an automatic device. The carotid amplification index (CAI), a quantitative estimation of the magnitude of central wave reflections, was measured noninvasively from pulse wave analysis using radial and carotid aplanation tonometry. RESULTS: In the overall population, age and mean arterial pressure represented 30.4%, 32.3%, and 5.6% of the variance of, respectively PP, PWV, and CAI. For the latter, body weight and heart rate represented 22.9% of variability. On the basis of logistic regression, AA were associated, in addition to age, plasma creatinine and HDL cholesterol levels, and tobacco consumption to three mechanical factors, increased PP, increased PWV, and low diastolic blood pressure, but not by CAI (adjusted odds ratio: 1.00; 95% confidence intervals: 0.99-1.01). CONCLUSION: In cross-sectional hypertensive populations, PP and PWV, but not CAI, are significantly and independently associated with cardiovascular amplications.

Drug treatment of hypertension: the reduction of pulse pressure does not necessarily parallel that of systolic and diastolic blood pressure.

Drug treatment of hypertension reduces systolic and diastolic blood pressure according to a well-established dose-response curve. Whether there is a parallel decrease in mean blood pressure and pulse pressure has not been investigated in the past Recent analysis of the literature and personal work indicates that, during drug treatment of hypertension, a significant decrease in systolic and diastolic blood pressure may be associated with an unchanged pulse pressure, a situation that might contribute to maintaining cardiovascular risk.

How can hypertensive patients be better treated? The contribution of combination therapy.

Recent studies demonstrated that target blood pressure (BP) in treated hypertensive patients should be below 140 mmHg for systolic blood pressure (SBP) and below 90 mmHg for diastolic blood pressure (DBP). However, population studies from several countries have demonstrated that in clinical practice the proportion of controlled hypertensive patients is less than 30%. In order to elucidate these questions in France we analysed a large population of 145,000 subjects examined at the Centre d'Investigations Préventives et Cliniques in Paris (IPC). Among those with high BP at the time of their IPC visit, only 20% received an antihypertensive treatment. Among those receiving an antihypertensive treatment, less than 27% (24% in men and 30% in women) presented with BP values less than 140 mmHg for SBP and less than 90 mmHg for DBP. This analysis also showed that 72% of hypertensive patients presented with at least one modifiable associated cardiovascular risk factor and that more than 30% of hypertensive men and more than 25% of hypertensive women presented with at least two associated risk factors. The use of combination therapies could help to increase the percentage of well-controlled hypertensive subjects. It has been shown that in order to reach this BP level, combination therapy should be used in more than two-thirds of the treated subjects. The trandolapril-verapamil combination is the first fixed combination of an angiotensin-converting enzyme inhibitor and a non-dihydropyridine calcium-channel blocker. Administered once daily, this combination reduces BP more than a classic monotherapy. The effects of the trandolapril-verapamil combination on risk factors are either neutral (metabolic parameters), or even beneficial (reduction in heart rate).

Influence of heart rate on mortality in a French population: role of age, gender, and blood pressure.

-The aim of the present study was to assess the effects of high heart rate on mortality in different subgroups in a French population according to age, gender, and blood pressure levels. We studied 19 386 subjects (12 123 men, 7263 women), aged 40 to 69 years, who had a routine health examination at the Centre d'Investigations Préventives et Cliniques (IPC) between 1974 and 1977. Heart rate (HR) measured by ECG was classified into 4 groups: HR1, <60; HR2, 60 to 80; HR3, 81 to 100; and HR4, >100 bpm. Mortality data were recorded for the period of 1974 through 1994. In both sexes, HR was a significant predictor of noncardiovascular mortality. In men, the relative risk (95% confidence interval) for cardiovascular death after adjustment for age and other risk factors in the HR2, HR3, and HR4 groups was 1.35 (1.01 to 1.80), 1.44 (1.04 to 2.00), and 2.18 (1.37 to 3.47), respectively, when compared with HR1. In women, HR did not influence cardiovascular mortality. The association of HR with cardiovascular mortality in men was (1) related to a strong association with coronary but not cerebrovascular mortality, (2) independent of age and hypertension, and (3) influenced by the level of pulse pressure; in patients with high pulse pressure (>65 mm Hg), accelerated HR was not associated with increased cardiovascular mortality. In conclusion, in a large French population, accelerated resting HR represents an independent predictor of noncardiovascular mortality in both genders, and of cardiovascular mortality in men, independent of age and the presence of hypertension. Further investigations are needed to explain the complex interactions between HR, pulse pressure, and cardiovascular complications.

Pulse pressure and cardiovascular mortality in normotensive and hypertensive subjects.

There is now increasing evidence that high pulse pressure, which is an indicator of large artery stiffness, is an independent risk factor for cardiovascular mortality, especially coronary mortality, in different populations. We have recently shown in a large French population that in male subjects aged 40 to 69 years, increased pulse pressure was a strong predictor of cardiovascular mortality, especially coronary mortality. In the present report, we analyzed the effect of pulse pressure in men and women of the same cohort after classifying them as normotensive (systolic blood pressure [SBP] <140 mm Hg and DBP <90 mm Hg) or hypertensive (SBP >/=160 mm Hg or DBP >/=95 mm Hg). After adjustment for age, mean blood pressure, and other risk factors, the relative risk (95% confidence limits) for cardiovascular mortality for an increase of 10 mm Hg of pulse pressure was 1.20 (1.01 to 1.44) in normotensives and 1.09 (1.03 to 1.14) in hypertensives. Cardiovascular and coronary death rates were similar in the group of normotensive men with a pulse pressure >50 mm Hg and in the group of hypertensive men with a pulse pressure <45 mm Hg. No association between cardiovascular mortality and pulse pressure was observed in either normotensive or hypertensive women (0.85 [0.60 to 1.21] and 1.0 [0. 91 to 1.11], respectively). Low mortality rates could explain this observation in normotensive but not in hypertensive women, in whom cardiovascular mortality rates were relatively high. Because a high pulse pressure in men is an independent predictor of cardiovascular mortality in both hypertensives and in those considered as having normal blood pressure, this parameter could aid in evaluating cardiovascular risk.

Prevalence of cardiovascular risk factors in a French population.

UNLABELLED: STUDY ON THE IDENTIFICATION OF CARDIOVASCULAR RISK FACTORS: Identification of cardiovascular risk factors and the estimation of their prevalence in different populations is an important aim of preventive medicine. We analysed the data from 58,803 volunteers who were subjected to systematic health examinations in the Centre d'Investigations Préventives et Cliniques in Paris during the period January 1991 to December 1993. In this report we present some results concerning the prevalence of the major cardiovascular risk factors and their associations with sex, age and the presence of hypertension. CONCLUSIONS: The present study clearly shows that before the age of 55 years, the prevalence of risk factors is higher in men than in women, whereas in postmenopausal women the risk-profile increases rapidly, reaching the level of men after the age of 65 years. The presence of multiple risk factors is much higher in hypertensive than in normotensive individuals. We also observed that more than two-thirds of the treated hypertensives had systolic/diastolic blood pressure levels of > 140/90 mmHg. These observations could contribute to the debate regarding the evaluation of global risk and therapeutic strategies in cardiovascular disease prevention.

Pulse pressure: a predictor of long-term cardiovascular mortality in a French male population.

Studies on the usefulness of blood pressure as a prognostic factor in cardiovascular disease have more often involved investigations of the levels of diastolic or systolic blood pressure. However, blood pressure may be divided into two other components: steady (mean pressure) and pulsatile (pulse pressure). In this study, the relationship of pulse pressure to cardiovascular mortality was investigated in 19 083 men 40 to 69 years old who were undergoing a routine systematic health examination and were being followed up after a mean period of 19.5 years. Subjects were divided into four groups according to age (40 to 54 and 55 to 69 years) and mean arterial pressure (<107 and > or =107 mm Hg). Each group was further divided into four subgroups according to the pulse pressure level. A wide pulse pressure (evaluated according to the quartile group or as a continuous quantitative variable) was an independent and significant predictor of all-cause, total cardiovascular, and, especially, coronary mortality in all age and mean pressure groups. No significant association between pulse pressure and cerebrovascular mortality was observed. In conclusion, in a large population of men with a relatively low cardiovascular risk, a wide pulse pressure is a significant independent predictor of all-cause, cardiovascular, and, especially, coronary mortality.