Harri Niinikoski

Early impairment of coronary flow reserve in young men with borderline hypertension

OBJECTIVES The purpose of this study was to investigate whether functional abnormalities in coronary vasomotion are present in young healthy asymptomatic men fulfilling the World Health Organization (WHO) criteria for borderline hypertension. BACKGROUND Previous studies have reported reduced coronary flow reserve in middle-aged subjects with sustained hypertension and hypertension-induced microvascular heart disease or left ventricular hypertrophy. METHODS Myocardial blood flow was measured at baseline and during dipyridamole-induced hyperemia by means of positron emission tomography and oxygen-15-labeled water in asymptomatic young men with borderline hypertension (group 1: n = 16, mean +/- SD age 37 +/- 4 years, 24-h ambulatory blood pressure 135 +/- 10/81 +/- 9 mm Hg) and matched healthy control subjects (group 2: n = 19, age 35 +/- 3 years, 24-h ambulatory blood pressure 119 +/- 8/69 +/- 8 mm Hg, p < 0.001). Left ventricular (LV) mass, dimensions and function were measured by echocardiography. RESULTS LV mass, dimensions and diastolic function were similar in the study groups. Baseline myocardial blood flow was similar (0.83 +/- 0.21 vs. 0.80 +/- 0.22 ml/g per min, group 1 vs. group 2, respectively, p = NS), and a significant increase in flow was detected after dipyridamole infusion (0.56 mg/kg body weight in 4 min intravenously) in both groups. However, the flow response to dipyridamole was significantly lower in group 1, leading to lower hyperemic flow in group 1 than in group 2 (2.85 +/- 1.20 vs. 3.80 +/- 1.44 ml/g per min, respectively). Consequently, the coronary flow response was lower in hypertensive than in normotensive men (3.46 +/- 1.23 vs. 4.99 +/- 2.5 ml/g per min, group 1 vs. group 2, respectively, p < 0.05). CONCLUSIONS These results demonstrate reduced coronary reactivity present in young asymptomatic men with borderline hypertension and no signs of hypertension-induced angina or left ventricular hypertrophy. Because baseline basal myocardial blood flow was unchanged, the reduction in coronary flow reserve depends on an impaired maximal vasodilator capacity.

Coronary Flow Reserve Is Impaired in Young Men With Familial Hypercholesterolemia

OBJECTIVES We sought to investigate whether functional abnormalities in coronary vasomotion exist in young adults by studying 15 men (age 31 +/- 8 years [mean +/- SD]) with familial hypercholesterolemia (FH) and a matched group of 20 healthy control subjects. BACKGROUND Precursors of morphologic coronary artery disease are known to be present in adolescents and young adults with a high risk factor profile. METHODS Myocardial blood flow was measured at the basal state and during dipyridamole-induced hyperemia using positron emission tomography and oxygen-15-labeled water. RESULTS Serum total and low density lipoprotein cholesterol concentrations were higher in the patients than in the control subjects (mean +/- SD): 7.7 +/- 1.9 versus 5.3 +/- 1.5 mmol/liter (298 +/- 73 vs. 205 +/- 58 mg/dl) and 6.1 +/- 1.8 versus 3.5 +/- 1.4 mmol/liter (236 +/- 70 vs. 135 +/- 54 mg/dl), respectively (both p < 0.001). The baseline myocardial blood flow was similar in the patients and control subjects: 0.92 +/- 0.24 versus 0.83 +/- 0.13 ml/g per min, respectively (p = 0.21). A significant increase in flow was observed in both groups after dipyridamole infusion, but the flow at maximal vasodilation was 29% lower in the patients: 3.19 +/- 1.59 versus 4.49 +/- 1.27 ml/g per min (p = 0.011). Consequently, coronary flow reserve (the ratio of hyperemia flow to basal flow) was 35% lower in the patients than in the control subjects: 3.5 +/- 1.6 versus 5.4 +/- 1.5 (p = 0.0008). Total coronary resistance during hyperemia was higher in the patients than in the control subjects: 36 +/- 25 versus 21 +/- 10 mm Hg/min per g per ml (p = 0.045). Coronary flow reserve was inversely associated with serum total cholesterol concentration: r = -0.43 (p = 0.009). CONCLUSIONS Coronary flow reserve is reduced in young men with FH, and, consequently, coronary resistance during hyperemia is increased. The results demonstrate very early impairment of coronary vasomotion in hypercholesterolemic patients.

Impact of Repeated Dietary Counseling Between Infancy and 14 Years of Age on Dietary Intakes and Serum Lipids and Lipoproteins The STRIP Study

Background— Atherosclerosis development might be delayed or prevented by dietary measures. The aims of the present study were to evaluate the effect of low-saturated-fat, low-cholesterol dietary counseling on fat intakes, growth, serum cholesterol values, and pubertal development in children and adolescents. Methods and Results— In the randomized prospective Special Turku Coronary Risk Factor Intervention Project (STRIP), a low-saturated-fat, low-cholesterol diet was introduced to intervention infants (n=540) at 7 months of age, and control children (n=522) received an unrestricted diet. Dietary intakes, serum cholesterol values, somatic growth, and development were followed up throughout childhood and adolescence. Saturated fat intakes, serum total cholesterol, and low-density lipoprotein cholesterol values were lower (P<0.001) in the intervention than in control children during the 14 years, whereas high-density lipoprotein cholesterol values in the 2 study groups showed no difference. Boys had lower total and low-density lipoprotein cholesterol concentrations than girls throughout childhood (P<0.001), and the intervention effect on serum cholesterol concentration was larger in boys than girls. The 2 study groups showed no difference in growth, body mass index, pubertal development, or age at menarche (median, 13.0 and 12.8 years in the intervention and control girls, respectively; P=0.52). The cholesterol values decreased as puberty progressed. Mean concentrations of total and high-density lipoprotein cholesterol decreased from ≈4.5 and ≈1.4 mmol/L, respectively, in Tanner stage 1 (prepubertal) boys to ≈3.9 and ≈1.1 mmol/L in Tanner stage 4 (late pubertal) boys. Conclusions— Repeated dietary counseling remains effective in decreasing saturated fat and cholesterol intake and serum cholesterol values at least until 14 years of age. Puberty markedly influences serum cholesterol concentrations.

Constantly low HDL-cholesterol concentration relates to endothelial dysfunction and increased in vivo LDL-oxidation in healthy young men

To test the hypothesis that low HDL-C concentration interferes with vascular endothelial function and lipoprotein oxidation, we measured endothelium-dependent flow mediated dilatation (FMD, %) of the brachial artery in young men (n=20) classified prospectively into two groups on basis of having either low or high HDL-C concentration over the past 2 years. As an estimate of in vivo low-density lipoprotein oxidation (ox-LDL), we measured LDL diene conjugation. FMD was present in the group with high HDL-C concentration, but impaired in the group with low HDL-C (5.5+/-3.2 vs 0.2+/-1.2%, P<0. 001). The group with high HDL-C level had significantly lower levels of ox-LDL compared to low HDL-C group (18.0+/-1.8 vs 22.9+/-4.4, P</=0.01). In all subjects, FMD correlated with HDL-C (r=0.59, P=0. 006), HDL(2)-C (r=0.62, P=0.004) and ox-LDL (r=-0.56, P=0.013) but not with HDL(3)-C (r=0.16, P=0.52). We conclude that constantly low HDL-C concentration is related with endothelial dysfunction and increased oxidative stress in healthy young men, consistent with the idea that HDL particles may protect endothelium and inhibit the oxidation of LDL. These findings may offer insight into increased atherosclerosis associated with low HDL-C levels.

Large-Artery Elastic Properties in Young Men Relationships to Serum Lipoproteins and Oxidized Low-Density Lipoproteins

Measures of arterial elasticity have been proposed as surrogate markers for asymptomatic atherosclerosis. We investigated the relations of serum lipoproteins, oxidized low-density lipoprotein (ox-LDL), and familial hypercholesterolemia (FH) to arterial elasticity among young men. As a marker of arterial elasticity we measured compliance in the thoracic aorta by using magnetic resonance imaging and in the common carotid artery by using ultrasound. LDL diene conjugation was used as a marker of ox-LDL. In study I, 25 healthy men (aged 29 to 39) were classified into 2 extreme groups according to previously measured high-density lipoprotein cholesterol to total cholesterol ratio (HDL-C/TC ratio). In study II, the healthy men were used as controls for 10 age matched asymptomatic patients with FH. In healthy men, the group with low HDL-C/TC ratio had decreased carotid artery compliance (2. 3+/-0.4% versus 1.9+/-0.5%/10 mm Hg, P=0.034). In univariate analysis, the compliance of the carotid artery associated with ox-LDL (r =-0.49, P=0.016) and HDL-C/TC ratio (r=0.41, P=0.040). In multivariate regression analyses, ox-LDL was the only independent determinant for compliance of the carotid artery (P=0.016). Aortic elasticity was not related to standard lipid variables, but the compliance of the ascending aorta associated with ox-LDL (r=-0.44, P=0.030). In FH patients, arterial elasticity was similar to that in controls. We conclude that elasticity of the common carotid artery is affected by serum lipid profile in young men. The current study demonstrates for the first time an in vivo association between ox-LDL and arterial elasticity suggesting that oxidative modification of LDL may play a role in the alteration of arterial wall elastic properties.

Association of Physical Activity With Vascular Endothelial Function and Intima-Media Thickness

Background— Impairment of vascular endothelial function and increased intima-media thickness (IMT) are important early steps in atherogenesis. Longitudinal data on the effect of physical activity on endothelial function and IMT in healthy adolescents are lacking. We investigated prospectively the association of leisure-time physical activity with endothelial function (brachial artery flow-mediated dilatation; FMD) and aortic IMT in adolescents. Methods and Results— FMD and IMT were measured with ultrasonography at 13 (n=553), 15 (n=531), and 17 (n=494) years of age in adolescents participating in a longitudinal atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children). Mean aortic IMT, maximum FMD, and total FMD response (area under the dilatation curve 40 to 180 seconds after hyperemia) were calculated. Leisure-time physical activity was assessed with a questionnaire, and metabolic equivalent (MET) hours per week of leisure-time physical activity were calculated by multiplying weekly mean exercise intensity, duration, and frequency. Leisure-time physical activity was directly associated with endothelial function (P for maximum FMD=0.0021, P for total FMD response=0.0036) and inversely with IMT (P=0.011) after adjustment for age, sex, body mass index, high-density lipoprotein/total cholesterol, systolic blood pressure, and C-reactive protein and regarding FMD brachial artery diameter. Sedentary adolescents who increased their leisure-time physical activity from <5 to >5 (IMT) or >30 (maximum FMD) MET h/wk between 13 and 17 years of age had an increased maximum FMD (P=0.031) and decreased progression of IMT (P=0.047) compared with adolescents who remained sedentary. IMT progression was attenuated in persistently active adolescents compared with those who became sedentary (P=0.0072). Conclusions— Physical activity is favorably associated with endothelial function and IMT in adolescents. Importantly, a moderate increase in physical activity is related to decreased progression of IMT. A physically active lifestyle seems to prevent the development of subclinical atherosclerotic vascular changes in healthy adolescents. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00223600 (STRIP19902010).

Ideal Cardiovascular Health in Adolescence Effect of Lifestyle Intervention and Association With Vascular Intima-Media Thickness and Elasticity (The Special Turku Coronary Risk Factor Intervention Project for Children [STRIP] Study)

Background— In the Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) study, repeated dietary counseling introduced in infancy and maintained until 20 years of age has led to lower intakes of saturated fat and serum low-density lipoprotein cholesterol. In this study, we examined prospectively the intervention effects on the ideal cardiovascular health concept recently described by the American Heart Association. Additionally, we investigated the association between the concept and vascular intima-media thickness and elasticity in adolescence. Methods and Results— In adolescents participating in the longitudinal, randomized, atherosclerosis-prevention STRIP study, complete data on ideal cardiovascular health metrics were available at 15 (n=394), 17 (n=376), and 19 (n=298) years of age. Aortic intima-media thickness and elasticity were measured with ultrasonography at the same ages. None of the adolescents had all 7 ideal cardiovascular health metrics. At least 5 ideal metrics was found in 60.2%, 45.5%, and 34.2% of the adolescents at 15, 17, and 19 years of age, respectively. Adolescents in the control group had an increased risk of low ideal cardiovascular health (⩽3 metrics) compared with the intervention adolescents (risk ratio=1.35; 95% confidence interval=1.04–1.77). The number of ideal cardiovascular health metrics was inversely associated with aortic intima-media thickness (P<0.0001) and directly associated with elasticity (P=0.045). The risk of having high intima-media thickness (>85th percentile) was nearly 2-fold in adolescents with a low number of metrics (⩽3) compared with those with a higher score (risk ratio=1.78; 95% confidence interval=1.31–2.43). Conclusions— Ideal cardiovascular health as determined by the AHA can be promoted in adolescents. The ideal cardiovascular health concept is beneficially associated with vascular health already in adolescence, supporting the relevance of targeting these metrics as part of primordial prevention. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00223600Background —In the STRIP study, repeated dietary counseling introduced in infancy and maintained until age 20 has led to lower intakes of saturated fat and serum LDL-cholesterol. In this study, we examined prospectively the intervention effects on the ideal cardiovascular health concept recently described by the AHA. Additionally, we investigated association of the concept with vascular intima-media thickness (IMT) and elasticity in adolescence. Methods and Results —In adolescents participating in the longitudinal, randomized atherosclerosis prevention STRIP study, complete data on ideal cardiovascular health metrics were available at age 15 (n=394), 17 (n=376) and 19 (n=298). Aortic IMT and elasticity were measured with ultrasonography at same ages. None of the adolescents had all 7 ideal cardiovascular health metrics. At least 5 ideal metrics was found in 60.2%, 45.5% and 34.2% of the adolescents at age 15, 17 and 19, respectively. Adolescents in the control group had an increased risk of low ideal cardiovascular health (≤3 metrics) compared with the intervention adolescents (RR=1.35, 95%CI=1.04-1.77). Number of the ideal cardiovascular health metrics was inversely associated with aortic IMT (p 85 th percentile) was nearly two fold in adolescents with low number of the metrics (≤3) compared with those with a higher score (RR=1.78, 95%CI=1.31-2.43). Conclusions —Ideal cardiovascular health as determined by the AHA can be promoted in adolescents. The ideal cardiovascular health concept is beneficially associated with vascular health already in adolescence supporting the relevance of targeting these metrics as part of primordial prevention. Clinical Trial Registration Information —ClinicalTrials.gov, STRIP19902010. Unique Identifier: NCT00223600.

Association of Physical Activity With Vascular Endothelial Function and Intima-Media Thickness A Longitudinal Study in Adolescents

Background— Impairment of vascular endothelial function and increased intima-media thickness (IMT) are important early steps in atherogenesis. Longitudinal data on the effect of physical activity on endothelial function and IMT in healthy adolescents are lacking. We investigated prospectively the association of leisure-time physical activity with endothelial function (brachial artery flow-mediated dilatation; FMD) and aortic IMT in adolescents. Methods and Results— FMD and IMT were measured with ultrasonography at 13 (n=553), 15 (n=531), and 17 (n=494) years of age in adolescents participating in a longitudinal atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children). Mean aortic IMT, maximum FMD, and total FMD response (area under the dilatation curve 40 to 180 seconds after hyperemia) were calculated. Leisure-time physical activity was assessed with a questionnaire, and metabolic equivalent (MET) hours per week of leisure-time physical activity were calculated by multiplying weekly mean exercise intensity, duration, and frequency. Leisure-time physical activity was directly associated with endothelial function (P for maximum FMD=0.0021, P for total FMD response=0.0036) and inversely with IMT (P=0.011) after adjustment for age, sex, body mass index, high-density lipoprotein/total cholesterol, systolic blood pressure, and C-reactive protein and regarding FMD brachial artery diameter. Sedentary adolescents who increased their leisure-time physical activity from <5 to >5 (IMT) or >30 (maximum FMD) MET h/wk between 13 and 17 years of age had an increased maximum FMD (P=0.031) and decreased progression of IMT (P=0.047) compared with adolescents who remained sedentary. IMT progression was attenuated in persistently active adolescents compared with those who became sedentary (P=0.0072). Conclusions— Physical activity is favorably associated with endothelial function and IMT in adolescents. Importantly, a moderate increase in physical activity is related to decreased progression of IMT. A physically active lifestyle seems to prevent the development of subclinical atherosclerotic vascular changes in healthy adolescents. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00223600 (STRIP19902010).

Sucrose Intake since Infancy and Dental Health in 10-Year-Old Children

The dental health of children in western countries has improved without a concomitant decrease in the mean sucrose consumption. Our aim was to analyse the association of long-term sucrose consumption with dental health in children representing the highest (n = 33, 18 boys) and the lowest 5 percentiles (n = 33, 21 boys) of sucrose intake, in a study where food consumption was prospectively recorded from infancy to 10 years of age. The sum of decayed, missing and filled teeth in the primary (dmft) and permanent (DMFT) teeth was assessed. Children’s sucrose intake in the high intake group was constantly higher than in their counterparts (p < 0.001), and already exceeded 10% of energy intake (E %) at 2 years of age. The mean ± SD of the dmft + DMFT scores was higher in the high than in the low sucrose intake group (3.9 ± 3.9 and 1.9 ± 2.5, respectively; p = 0.032). We conclude that a persistently high sucrose intake increases the risk of dental caries in children.

Ideal Cardiovascular Health in Adolescence: Effect of Lifestyle Intervention and Association with Vascular Intima-Media Thickness and Elasticity (the STRIP Study)

Background— In the Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) study, repeated dietary counseling introduced in infancy and maintained until 20 years of age has led to lower intakes of saturated fat and serum low-density lipoprotein cholesterol. In this study, we examined prospectively the intervention effects on the ideal cardiovascular health concept recently described by the American Heart Association. Additionally, we investigated the association between the concept and vascular intima-media thickness and elasticity in adolescence. Methods and Results— In adolescents participating in the longitudinal, randomized, atherosclerosis-prevention STRIP study, complete data on ideal cardiovascular health metrics were available at 15 (n=394), 17 (n=376), and 19 (n=298) years of age. Aortic intima-media thickness and elasticity were measured with ultrasonography at the same ages. None of the adolescents had all 7 ideal cardiovascular health metrics. At least 5 ideal metrics was found in 60.2%, 45.5%, and 34.2% of the adolescents at 15, 17, and 19 years of age, respectively. Adolescents in the control group had an increased risk of low ideal cardiovascular health (⩽3 metrics) compared with the intervention adolescents (risk ratio=1.35; 95% confidence interval=1.04–1.77). The number of ideal cardiovascular health metrics was inversely associated with aortic intima-media thickness (P<0.0001) and directly associated with elasticity (P=0.045). The risk of having high intima-media thickness (>85th percentile) was nearly 2-fold in adolescents with a low number of metrics (⩽3) compared with those with a higher score (risk ratio=1.78; 95% confidence interval=1.31–2.43). Conclusions— Ideal cardiovascular health as determined by the AHA can be promoted in adolescents. The ideal cardiovascular health concept is beneficially associated with vascular health already in adolescence, supporting the relevance of targeting these metrics as part of primordial prevention. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00223600Background —In the STRIP study, repeated dietary counseling introduced in infancy and maintained until age 20 has led to lower intakes of saturated fat and serum LDL-cholesterol. In this study, we examined prospectively the intervention effects on the ideal cardiovascular health concept recently described by the AHA. Additionally, we investigated association of the concept with vascular intima-media thickness (IMT) and elasticity in adolescence. Methods and Results —In adolescents participating in the longitudinal, randomized atherosclerosis prevention STRIP study, complete data on ideal cardiovascular health metrics were available at age 15 (n=394), 17 (n=376) and 19 (n=298). Aortic IMT and elasticity were measured with ultrasonography at same ages. None of the adolescents had all 7 ideal cardiovascular health metrics. At least 5 ideal metrics was found in 60.2%, 45.5% and 34.2% of the adolescents at age 15, 17 and 19, respectively. Adolescents in the control group had an increased risk of low ideal cardiovascular health (≤3 metrics) compared with the intervention adolescents (RR=1.35, 95%CI=1.04-1.77). Number of the ideal cardiovascular health metrics was inversely associated with aortic IMT (p 85 th percentile) was nearly two fold in adolescents with low number of the metrics (≤3) compared with those with a higher score (RR=1.78, 95%CI=1.31-2.43). Conclusions —Ideal cardiovascular health as determined by the AHA can be promoted in adolescents. The ideal cardiovascular health concept is beneficially associated with vascular health already in adolescence supporting the relevance of targeting these metrics as part of primordial prevention. Clinical Trial Registration Information —ClinicalTrials.gov, STRIP19902010. Unique Identifier: NCT00223600.