Kathryn Bean

Telomere Length as an Indicator of Biological Aging: The Gender Effect and Relation With Pulse Pressure and Pulse Wave Velocity

Chronological age is the primary determinant of stiffness of central arteries. Increased stiffness is an independent indicator of cardiovascular risk. The aim of this study was to determine whether telomere length, a possible index of biological aging, provides a better account than chronological age for variation in arterial stiffness, evaluated by measuring pulse pressure and aortic pulse wave velocity. The study population included 193 French subjects (120 men, 73 women), with a mean age of 56±11 years, who were not on any antihypertensive medications. Telomere length was evaluated in white blood cells by measuring the mean length of the terminal restriction fragments. Age-adjusted telomere length was longer in women than in men (8.67±0.09 versus 8.37±0.07 kb;P =0.016). In both genders, telomere length was inversely correlated with age (P <0.01). Multivariate analysis showed that in men, but not in women, telomere length significantly contributed to pulse pressure and pulse wave velocity variations. In conclusion, telomere length provides an additional account to chronological age of variations in both pulse pressure and pulse wave velocity among men, such that men with shorter telomere length are more likely to exhibit high pulse pressure and pulse wave velocity, which are indices of large artery stiffness. The longer telomere length in women suggests that for a given chronological age, biological aging of men is more advanced than that of women.

Short Telomeres Are Associated With Increased Carotid Atherosclerosis in Hypertensive Subjects

Abstract—Recent studies have shown that individuals with shorter telomeres present a higher prevalence of arterial lesions and higher risk of cardiovascular disease mortality. As a group, patients with high blood pressure are at an increased risk for cardiovascular diseases. However, some hypertensive patients are more prone than others to atherosclerotic lesions. The main objective of this study was to examine the relationship between telomere length, as expressed in white blood cells, and carotid artery atherosclerotic plaques in hypertensive males. Data from 163 treated hypertensive men who were volunteers for a free medical examination were analyzed. Extracranial carotid plaques were assessed with B-mode ultrasound. Telomere length was measured from DNA samples extracted from white blood cells. The results of this study show that telomere length was shorter in hypertensive men with carotid artery plaques versus hypertensive men without plaques (8.17±0.07 kb versus 8.46±0.07 kb; P <0.01). Multivariate analysis showed that in addition to age, telomere length was a significant predictor of the presence of carotid artery plaques. The findings from this study suggest that in the presence of chronic hypertension, which is a major risk factor for atherosclerotic lesions, shorter telomere length in white blood cells is associated with an increased predilection to carotid artery atherosclerosis.

A Decrease in Diastolic Blood Pressure Combined With an Increase in Systolic Blood Pressure Is Associated With a Higher Cardiovascular Mortality in Men

OBJECTIVES The study evaluated the risk of cardiovascular mortality according to combined spontaneous (non-treatment-related) changes in both systolic and diastolic blood pressure (BP). BACKGROUND Long-term longitudinal changes in blood pressure may be a more accurate determinant of cardiovascular risk since changes in systolic or diastolic blood pressure over a period of time reflect the evolution of arterial and arteriolar alterations. METHODS Two independent French male cohorts were studied: the IPC cohort (Investigations Préventives et Cliniques) composed of 15,561 men aged 20 to 82 years who had had two visits spaced four to 10 years apart, and the Paris Prospective Study composed of 6,246 men aged 42 to 53 years, examined annually for a period of four years. None of the subjects were taking antihypertensive medication. Annual changes in BP were estimated, and subjects were divided into groups according to the increase, lack of change, or decrease of systolic or diastolic BP. Nine groups were formed by combining the changes of systolic and diastolic BP. Cardiovascular mortality was assessed for a mean period of 13.5 years for the IPC Study and 17 years for the Paris Prospective Study. RESULTS In both cohorts, after adjustment for age and major risk factors, the group with an increase in systolic and a decrease in diastolic BP presented the highest relative risk of cardiovascular mortality compared to the group with no changes in either systolic or diastolic BP (relative risk: 2.07 [1.05 to 4.06] in the IPC Study and 2.16 [1.16 to 4.01] in the Paris Prospective Study). CONCLUSIONS Assessment of spontaneous changes of BP over a long period of time can contribute to the evaluation of cardiovascular risk. Subjects whose systolic BP increased while their diastolic BP decreased had the highest cardiovascular risk independently of absolute values of BP or other risk factors.

Carotid plaques, but not common carotid intima-media thickness, are independently associated with aortic stiffness

Objective It has been suggested that non-invasive aortic stiffness measurements can be used as an indicator of atherosclerosis. The relationships of arterial stiffness with arterial wall hypertrophy and atherosclerosis however, have rarely been investigated in large-scale studies. The present study reports the associations of carotid arterial structure assessed by B-mode ultrasound with carotid-femoral pulse-wave velocity in hypertensive and non-hypertensive subjects. Design and methods Free health examinations were performed on 564 subjects (age 58.2 ± 10.8 years, 31.9% of women, 53.2% of all were hypertensive). Carotid–femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid ultrasound examination included measurements (at sites free of plaques) of intima–media thickness (IMT) at the common carotid arteries (CCA), CCA-lumen diameter, and assessment of atherosclerotic plaques in the extracranial carotid arteries. Results Subjects with carotid plaques had significantly higher mean sex-adjusted values of PWV than those without carotid plaques (12.7 ± 0.2 versus 11.1 ± 0.1 m/s, P < 0.001). Multivariate analyses showed that this association was independent of sex, age, height, body mass index, mean blood pressure, pulse pressure, diabetes, hypercholesterolaemia and smoking habits (P < 0.009). PWV was positively associated with CCA-IMT and CCA-lumen diameter in sex-adjusted analysis (partial correlation coefficients (r) were respectively 0.39 and 0.42, P < 0.001 for each). However, the association of PWV with CCA-IMT, but not that with CCA-lumen diameter, disappeared after further adjustment for age and blood pressure measurements (mean blood pressure and/or pulse pressure). Conclusion This study shows that there is a differential association of PWV with CCA-IMT and carotid plaques. The nature of the independent positive association between atherosclerosis and arterial stiffness should be thoroughly investigated.

Cardiovascular Mortality in Overweight Subjects: The Key Role of Associated Risk Factors

The role of obesity and overweight as independent risk factors for cardiovascular disease is still debated. The aim of this study was to evaluate the impact of overweight on cardiovascular mortality according to the presence or absence of associated risk factors. This study included 139 562 men and 104 236 women, aged 18 to 95 years, who had a standard health checkup at the IPC Center between 1972 and 1988. The follow-up period for mortality ended in December 1997. In both genders, the prevalence of hypertension, diabetes, and hypercholesterolemia increased with body mass index (P<0.001). When compared with subjects with a body mass index <25 kg/m2 without associated risk factors, overweight subjects without associated risk factors did not have an increased risk of cardiovascular mortality. Risk of cardiovascular death increased significantly when overweight was associated with hypertension alone [hazard ratio: 2.05 (1.71 to 2.46) in men; 2.15 (1.48 to 3.11) in women]. In both genders, the association of overweight with diabetes alone or hypercholesterolemia alone did not increase the risk. By contrast, in the presence of hypertension, cardiovascular mortality dramatically increased in overweight subjects with hypercholesterolemia [hazard ratio: 2.65 (2.20 to 3.19) in men, 2.57 (1.80 to 3.68) in women] or diabetes [hazard ratio: 3.01 (2.29 to 3.95) in men; 4.50 (2.67 to 7.58) in women]. The data suggest that the presence of high blood pressure in overweight subjects is the key factor leading to a significant increase in cardiovascular mortality. Because overweight significantly increases the prevalence of associated risk factors, especially hypertension, it should be considered as a major cardiovascular risk determinant.

Cardiovascular Mortality in Hypertensive Men According to Presence of Associated Risk Factors

Abstract—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 29640 normotensive men without ARFs (reference group) and 60343 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/m2, 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.

Echogenic carotid plaques are associated with aortic arterial stiffness in subjects with subclinical carotid atherosclerosis.

Abstract—A better understanding of the interrelationships between the structure and function of the large arteries would lead to optimize cardiovascular disease prevention strategies. In this study, we investigated the relationships of aortic arterial stiffness assessed by carotid-femoral pulse-wave velocity (PWV), with carotid plaque echogenicity assessed by B-mode ultrasound. We analyzed 561 subjects (without coronary heart disease or stroke) who were volunteers for free health examinations (age, 58.3±10.8 years; 32.6% women). Extracranial carotid plaque echogenicity was graded from 1 (plaque appearing black or almost black) to 4 (plaque appearing white or almost white) according to the Gray-Weale classification. Plaques of grades 1 and 2 were defined as echolucent plaques, and plaques of grades 3 and 4 were defined as echogenic plaques. Fifty-one subjects (9.1%) had echolucent carotid plaques, 109 (19.4%) had echogenic plaques, and 401 (71.5%) had no plaques. Subjects with echogenic plaques had higher PWV mean (12.9±2.8 m/s) compared with those without plaques (11.1±2.3 m/s, P <0.001) and compared with those with echolucent plaques (11.3±2.3 m/s, P <0.01). The PWV means in subjects without plaques and those with echolucent plaques were similar and not statistically different (P =0.55). When multivariate adjustment for major known cardiovascular risk factors was performed, these results were not markedly modified. Similar patterns of results were also observed in many subgroups according to age, gender, and hypertensive status. This study provides the first evidence that echogenic but not echolucent carotid plaques are associated with aortic arterial stiffness. This association applies to individuals with normal blood pressure and those with elevated blood pressure. Assessment of the joint and interaction effects of plaque morphology and arterial stiffness on the occurrence of cardiovascular events would permit a better identification of high-risk subjects.

Combined effects of heart rate and pulse pressure on cardiovascular mortality according to age

Objectives The aim of the study was to assess the combined effects of pulse pressure (PP) and heart rate (HR) on cardiovascular mortality in a large French population. Design The study population was composed of 125 513 men and 96 301 women aged 16–95 years who had a health check-up at the IPC Center between January 1978 and December 1988. Subjects taking antihypertensive treatment were excluded. Mortality was assessed for an 8-year period. HR and PP were classified into three groups. HR groups were:< 60, 60–79 and ⩾ 80 beats per minute (bpm). PP groups were:< 50, 50–64 and ⩾ 65 mmHg. Results In men, PP and HR were both positively associated with cardiovascular mortality risk. In women, mean arterial pressure (MAP) but not PP or HR was associated with cardiovascular mortality. In men, a combined elevation of PP and HR was associated with an important increase of cardiovascular mortality risk. The group with the highest PP and the highest HR had a 4.8-fold increase in cardiovascular mortality risk as compared to the reference group (PP < 50 mmHg and HR < 60 bpm). This effect was more pronounced in younger men (5.4-fold increase) than in older men (3.7-fold increase), as compared to the reference groups of the same age. In women, the combined effects of PP and HR on cardiovascular mortality were not significant. Conclusion A combined elevation of the two components of pulsatile arterial stress is associated with an important increase in cardiovascular mortality in men, especially in younger men. In women, steady-state stress (evaluated primarily by MAP), but not pulsatile stress, is an important determinant of cardiovascular mortality.

Role of modifiable risk factors in life expectancy in the elderly.

Objective The aim of the present study was to evaluate the role of ‘modifiable’ risk factors, assessed between the ages of 60 and 70 years, in late survival. Design The study population included subjects aged 60–70 years, who had a standard health examination at the IPC Center, and who could potentially reach the age of 80 years for men and 85 years for women at the end of the follow-up period. Methods The role of ‘modifiable’ risk factors was assessed by comparing subjects who died before the age of 80 years for men (n = 1333) and before 85 years for women (n = 543) to subjects who survived beyond these ages (3681 men, 1910 women). Multivariate analyses were conducted to determine which parameters were independently associated with survival to an advanced age. Results The multivariate analysis showed a decreased probability of late survival with higher pulse pressure (P < 0.0001), higher heart rate (P < 0.002), higher glycemia (P < 0.0034), and an increased probability with regular physical activity (P < 0.0001). A significant interaction between heart rate and gender (P < 0.01) was observed, indicating that heart rate was a predictor of late survival in men but not in women. Body mass index, cholesterol and triglyceride levels, and diastolic blood pressure and tobacco smoking were not associated with late survival in this population. Conclusions A systematic search for certain risk factors in an elderly patient can have a significant impact on late survival and can lead to the establishment of priority goals, such as increasing physical activity and reducing blood pressure, heart rate and glycemia.

RESTING HEART RATE IN OLDER PEOPLE: A PREDICTOR OF SURVIVAL TO AGE 85

3. Lieberman MA, Fisher L. The effects of family conflict resolution and decision making on the provision of help for an elder with Alzheimer’s disease. Gerontologist 1999;39:159–166. 4. Zanetti O, Frisoni GB, Bianchetti A et al. Depressive symptoms of Alzheimer caregivers are mainly due to personal rather than patient factors. Int J Geriatr Psychiatry 1998;13:358–367. 5. Rabins P, Blacker D, Bland W et al. Practice guideline for the treatment of patients with Alzheimer’s disease and other dementias of late life. Am Psychiatric Assoc Am J Psychiatry 1997;154(5 Suppl):1–39.