Assessment of cardiovascular risk in primary health care.

OBJECTIVE: This study aimed at investigating whether cardiovascular risk factors and their impact on total risk estimation differ between men and women. DESIGN: Cross-sectional cohort study. SUBJECTS: Finnish cardiovascular risk subjects (n = 904) without established cardiovascular disease, renal disease, or known diabetes. MAIN OUTCOME MEASURES: Ankle-brachial index (ABI), estimated glomerular filtration rate (eGFR), oral glucose tolerance test, and total cardiovascular risk using SCORE risk charts. RESULTS: According to the SCORE risk charts, 27.0% (95% CI 23.1-31.2) of the women and 63.1% (95% CI 58.3-67.7) of the men (p < 0.001) were classified as high-risk subjects. Of the women classified as low-risk subjects according to SCORE, 25% had either subclinical peripheral arterial disease or renal insufficiency. CONCLUSIONS: The SCORE system does not take into account cardiovascular risk factors typical in women, and thus underestimates their total cardiovascular risk. Measurement of ABI and eGFR in primary care might improve cardiovascular risk assessment. especially in women.

Both hypertensive men and women are inadequately treated in Finnish general practice.

A general comprehension is that men are treated poorer than women. This study was planned to assess the Finnish hypertensive care with interests in possible hypertensive and cardiovascular control differences between men and women. A cross-sectional study was carried out by nationwide questionnaire survey of 714 consecutive drug-treated hypertensive patients having visited general practice during autumn 2006. Mean (SD) blood pressure (BP) of the women was 148.3 (21.1)/86.8 (11.7) mm Hg and of men 146.5 (19.5)/89.0 (11.8). Women had significantly lower diastolic BP (P = .016). The mean LDL cholesterol of women was 2.94 (0.91) mmol/L and of men 2.95 (0.94) mmol/L (P = .94). The blood pressure target <140/85 mm Hg was reached by 25% of the women and 23% of the men (P = .70). Of the women 30.7% and of the men 31.1% reached low-density lipoprotein (LDL)-cholesterol <2.5 mmol/L. Women used more diuretics than men (P = .06). No significant difference was seen between women and men in the number of patients reaching the target pressure <140/85 mm Hg, although diastolic blood pressure of the women was significantly lower. Hypertensive women and men were equally undertreated, and regardless of the sex, antihypertensive and hyperlipidemic control of hypertensive patients should be intensified.

Low-dose acetylsalicylic acid and blood pressure control in drug-treated hypertensive patients.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase blood pressure (BP) and potentially reduce the efficacy of several antihypertensive drugs. We evaluated the effect of low-dose acetylsalicylic acid (ASA) on BP control in drug-treated hypertensive patients in a primary care population. DESIGN/METHODS: Nine hundred and five successive patients aged 25­91 years (mean 65.5 years) from 15 health centers in south-west Finland were studied. The patients were on antihypertensive monotherapy (45.7%) or on combination therapy (54.3%). Office BP was measured twice with a 2-min interval after at least a 10-min rest using an ordinary sphygmomanometer. RESULTS: Patients receiving ASA (n = 246) showed lower diastolic BP (83.9 ± 9.0 vs. 87.0 ± 9.6 mmHg; P < 0.001) compared with those who were not using any NSAIDs (n = 659). No significant difference in systolic BP was observed between the groups. As a result, pulse pressure was slightly higher in the ASA group (66.9 ± 18.9 vs. 63.3 ± 17.7 mmHg, P = 0.01). Mean arterial pressure was lower in the ASA group (106.2 ± 10.6 vs. 108.1 ± 10.4 mmHg, P = 0.02). In a stepwise linear multivariate model, ASA remained a significant predictor of lower diastolic BP even after the adjustment with the confounding effects of age and sex. CONCLUSION: According to our population-based study low-dose ASA does not have deleterious effects on BP control in drug-treated hypertensive patients.

The assessment of total cardiovascular risk in hypertensive subjects in primary care.

BACKGROUND: Recently published guidelines emphasize that detection of any subclinical target organ damage in hypertensive subjects should be regarded as a sign of high cardiovascular risk. AIM: To assess the ability of conventional multivariable cardiovascular disease risk prediction tools and high-sensitivity C-reactive protein (hs-CRP) to identify hypertensive subjects with target organ damage. METHODS: Ankle-brachial index (ABI), estimated glomerular filtration rate (eGFR), electrocardiographically determined left ventricular hypertrophy (ECG-LVH), and base-line variables were measured in hypertensive subjects aged 45-70 years without established cardiovascular or renal disease or known diabetes. RESULTS: Of the 495 subjects, 123 (24.8% (95% CI 21.1-28.9)) had ABI <1.00, 81 (16.4% (95% CI 13.2-19.9)) had ECG-LVH, and 41 (8.3% (95% CI 6.0-11.1)) had eGFR <60 mL/min/1.73 m(2). In patients with SCORE <5% or Framingham risk <20%, any sign of target organ damage was found in 46% and 49% of patients, respectively. CONCLUSION: Assessment of ECG-LVH, ABI, and eGFR reclassifies a significant number of hypertensive patients to the high-risk category as compared to SCORE and Framingham risk prediction tools only.

Ankle-brachial index is lower in hypertensive than in normotensive individuals in a cardiovascular risk population.

BACKGROUND: Hypertension is an established risk factor for peripheral arterial disease (PAD), but the prevalence of this condition in hypertensive patients without comorbidities is unknown. METHODS: In this study, we assess the prevalence and factors associated with PAD, and the usefulness of ankle-brachial index (ABI) in evaluating cardiovascular risk in hypertensive patients without cardiovascular or renal disease or previously known diabetes mellitus. We measured ABI in 972 nonclaudicant patients with hypertension, newly diagnosed glucose disorders, metabolic syndrome, obesity or a 10-year risk of cardiovascular disease death of 5% or more according to the Systematic Coronary Risk Evaluation System. RESULTS: The prevalence of PAD (defined as ABI < or =0.90) and borderline PAD (defined as ABI 0.91-1.00) in hypertensive patients was 7.3% (39/532) and 23.7% (126/532), respectively. In a multivariate model, hypertension remained an independent factor associated with PAD (adjusted odds ratio 3.20; 95% confidence interval 1.56-6.58). There was no association between PAD and metabolic risk factors. SBP and pulse pressure increased linearly across subgroups of ABI (normal 0.91-1.00 and < or =0.90) in hypertensive patients (P < 0.001). CONCLUSION: Subclinical PAD is common in hypertensive patients even without comorbidities. The measurement of ABI is an efficient method to identify patients with increased cardiovascular risk and worth performing to hypertensive patients, particularly those with pulse pressure above 65 mmHg. Uniform criterions of defining PAD and borderline PAD would aid physicians in clinical decision-making.

Treatment of hypertension in Finnish general practice seems unsatisfactory despite evidence-based guidelines.

OBJECTIVES: This study was performed to clarify whether treatment of hypertension and concomitant risk factors in Finland has improved after the introduction of national evidence-based guidelines for antihypertensive treatment in 2002. Changes in the other cardiovascular risk factors of the Finnish hypertensive patients were also assessed. DESIGN: Nationwide questionnaire survey of consecutive hypertensive patients having met by general practitioners during a given week in autumn 2006. SETTING: Finnish general practice offices in primary care. SUBJECTS: Data from 715 hypertensive patients, 358 men and 357 women, from 72 general practice offices. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure, serum lipids, smoking status and information about other risk factors. RESULTS: The mean blood pressure of the patients was 147/88 mmHg. Eighty-one men (23%) and 85 women (24%) reached the treatment goal of 140/85 mmHg or less. Low-density lipoprotein-cholesterol level below 2.5 mmol/l was reached by 104 (29%) men and 104 (29%) women. Only 13% of the hypertensive patients (16.8% of the men and 9.2% of the women) were active smokers. CONCLUSIONS: Roughly three-quarters of hypertensive patients still failed to reach the blood pressure target of 140/85 mmHg recommended by the current Finnish Hypertension Guidelines. Our results are disappointing, considering the homogenous Finnish population and thorough primary healthcare system. Although the mean serum cholesterol concentration of the hypertensive population exceeded target values set by the guidelines, a clear improvement compared with early 21st century is seen. Also smoking has diminished considerably.

The effects of a 6-month sodium restriction on cardiac autonomic function in patients with mild to moderate essential hypertension.

BACKGROUND: The blood pressure-lowering mechanism of low-sodium diet is not fully understood. METHODS: We assessed the effects of salt restriction on cardiac parasympathetic function as measured by heart-rate variability (HRV) in mild to moderate hypertensive patients. Eighty patients were randomized to a 6-month low- (N = 40) or normal (N = 40) sodium diet and a 24-h electrocardiogram (ECG) was carried out in the beginning of the study and at 6 months. Five time-domain and six frequency-domain HRV variables were analyzed: mean RR interval, standard deviation of normal RR intervals, mean of the standard deviations of all RR intervals for 5-min segments of the entire recording, percentage of differences between adjacent normal RR intervals exceeding 50 ms, square root of the mean of squared differences between adjacent normal RR intervals, total (0.01-0.40 Hz), high frequency (HF, 0.15-0.40 Hz), low frequency (LF, 0.04-0.15 Hz), very LF (0.01-0.04 Hz) and LF/HF ratio. RESULTS: Although blood pressure diminished significantly (systolic blood pressure (SBP) from 149.9 +/- 14.7 mm Hg to 130.3 +/- 11.8 mm Hg, P < 0.001 and diastolic blood pressure (DBP) from 98.0 +/- 6.4 mm Hg to 87.1 +/- 6.2 mm Hg, P <0.001) after 6 months in the salt reduction group, no significant differences in the change between the groups could be detected. CONCLUSIONS: A moderate, prolonged dietary sodium restriction does not alter HRV. Therefore, mechanisms other than cardiac autonomic mechanisms are likely to predominate in the blood pressure-lowering effect of salt restriction.

Risk of upper gastrointestinal events with the use of various NSAIDs: a case-control study in a general population.

OBJECTIVE: The gastrointestinal (GI) safety of different non-steroidal anti-inflammatory drugs (NSAIDs) in a real-life setting remains ill defined. The aim of this study was to examine the risk of upper GI events associated with various NSAIDs in a general population. MATERIAL AND METHODS: A nationwide, register-based, matched case-control study was carried out in outpatient residents of Finland in 2000-04. Cases with upper GI events (n=9191) were drawn from the Hospital Discharge Register and individually matched to controls (n=41,780) from the Population Register. RESULTS: The semi-selective NSAIDs (nimesulide, nabumetone, meloxicam, etodolac) had the highest odds ratio for upper GI events even after adjusting for various potential confounders (adjusted odds ratio (AOR) 3.63; 95% CI 3.08-4.28), followed by non-selective (2.98; 2.70-3.29) and COX-2 selective NSAIDs (2.53; 2.09-3.07). When the current use of semi-selective NSAIDs was compared with that of non-selective and COX-2 selective NSAIDs, the AORs were 1.54 (1.13-2.09) and 1.67 (1.10-2.53), respectively. The AORs for the use of COX-2 selective NSAIDs did not differ statistically from the non-selective NSAIDs (AOR 0.92; 0.65-1.31). The AORs for individual NSAIDs varied across and within categories. CONCLUSIONS: As a group, the GI safety of the COX-2 selective NSAIDs was not demonstrated as definitively superior to non-selective NSAIDs. Semi-selective NSAIDs do not seem to offer any GI advantage over other NSAIDs.

Coronary reactivity, homocysteine and methylenetetrahydrofolate reductase gene variation in young men during pravastatin therapy.

High plasma homocysteine (Hcy) has been linked to impaired endothelial function. We investigated whether treatment with pravastatin affects the Hcy levels. Moreover, we studied whether the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism affects coronary vasomotion at baseline and during the treatment with pravastatin. Fifty-one healthy, mildly hypercholesterolemic men (mean age 35+/-4 years) attended this randomised, double-blind, placebo-controlled study. The volunteers were randomised into groups with 6-month treatment with pravastatin (40 mg/day, n=25) or placebo (n=26). Coronary blood flow measurements with positron emission tomography at rest and during adenosine infusion as well as biochemical analyses were done at baseline and at the end of the treatment period. The Hcy concentration decreased significantly during the pravastatin therapy (-0.81+/-1.46 micromol/l, p=0.01), but not during placebo (0.02+/-2.39 micromol/l, p=0.97). The MTHFR polymorphism did not affect the Hcy concentration or coronary flow indices. Neither did the MTHFR polymorphism modulate the effects of pravastatin on coronary vasomotion. In conclusion, a 6-month therapy with pravastatin decreases Hcy concentration in Finnish healthy young men. The MTHFR genotype is neither a determinant of baseline coronary flow indices nor does it modulate the effect of pravastatin on coronary reactivity.

NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland.

AIMS: To evaluate the risk of first myocardial infarction (MI) associated with the use of various non-steroidal anti-inflammatory drugs (NSAIDs) in the general population. METHODS AND RESULTS: We conducted a population-based matched case-control study over the years 2000-3 in outpatient residents of Finland. In the nationwide Hospital Discharge Register 33 309 persons with first time MI were identified. A total of 138 949 controls individually matched for age, gender, hospital catchment area, and index day were selected from the Population Register. For combined NSAIDs, the adjusted odds ratio for the risk of first MI with current use was 1.40 (95% CI, 1.33-1.48). The risk was similar for conventional (1.34; 1.26-1.43), semi-selective (etodolac, nabumetone, nimesulide, and meloxicam) (1.50; 1.32-1.71), and cyclo-oxygenase-2 (COX-2) selective NSAIDs (rofecoxib, celecoxib, valdecoxib, and etoricoxib) (1.31; 1.13-1.50). Age of current user did not consistently modify the risk. No NSAID was associated with an MI-protective effect. All durations from 1 to 180 days of conventional NSAIDs and from 31 to 90 days duration of COX-2 selective NSAIDs were associated with an elevated risk of MI. CONCLUSION: Current use of all NSAIDs is associated with a modest risk of first time MI.

A comparison of home measurement and ambulatory monitoring of blood pressure in the adjustment of antihypertensive treatment.

BACKGROUND: The purpose of this study was to compare home and ambulatory blood pressure (BP) in the adjustment of antihypertensive treatment. METHODS: After a 4-week washout period, patients whose untreated daytime diastolic ambulatory BP averaged > or = 85 mm Hg were randomized to be treated according to their ambulatory or home BP. Antihypertensive treatment was adjusted at 6-week intervals according to the mean daytime ambulatory diastolic BP or the mean home diastolic BP, depending on the patient's randomization group. If the diastolic BP stayed above 80 mm Hg, the physician blinded to randomization intensified hypertensive treatment. RESULTS: Ninety-eight patients completed the study. During the 24-week follow-up period both systolic and diastolic BP decreased significantly within both groups (P < .001). At the end of the study, the systolic/diastolic differences between ambulatory (n = 46) and home (n = 52) BP groups in home, daytime ambulatory, night-time ambulatory, and 24-h ambulatory BP changes averaged 2.6/2.6 mm Hg, 0.6/1.7 mm Hg, 1.0/1.4 mm Hg, and 0.6/1.5 mm Hg, respectively (P range .06 to .75) A nonsignificant trend to more intensive drug therapy in the ambulatory BP group and a nonsignificant trend to larger share of patients reaching (57.7% v 43.5%, P = .16) the target pressure in the home BP group was observed due to the 3.8 mm Hg difference in ambulatory and home diastolic BP at randomization. CONCLUSIONS: The adjustment of antihypertensive treatment based on either ambulatory or home BP measurement led to good BP control. No significant between-group differences in BP changes were seen at the end of the study. Additional research is needed to provide more conclusive results.

Genetic variant of the SREBF-1 gene is significantly related to cholesterol synthesis in man.

Sterol regulatory element binding proteins-1 and -2 (SREBPs) are transcription factors controlling lipid homeostasis in human cells. The G-allele carriers of the SREBF-1 gene C-G polymorphism in exon 18c and coding for glycine at the protein level (G952G) have shown to associate more frequently with obesity and type 2 diabetes than the C-allele carriers. However, the C-allele has suggested to be linked to dyslipidemia. Thus, our aim was to study effect of the SREBF-1 gene polymorphism (G952G) on sterol metabolism in man. Ninety-five subjects with moderate hypercholesterolemia participated in this study and 14 homozygous CC carriers of the SREBF-1 (G952G) gene were found. Plasma lathosterol concentration and lathosterol-to-cholesterol ratio, markers of endogenous cholesterol synthesis, were significantly higher in CC homozygous subject compared to others. Similarly muscle cholesterol (p=0.045) and lathosterol (p=0.054) concentrations were elevated in the CC homozygotes supporting the view that endogenous cholesterol synthesis rate is SREBF-1 genotype-dependent.

Effect of pravastatin on plasma sterols and oxysterols in men.

OBJECTIVES: The HMG-CoA reductase inhibitors, or statins, are well established in the prevention and treatment of coronary artery disease, mainly by lowering low-density lipoprotein (LDL) cholesterol levels. These compounds are structurally similar, but differ in their lipophilicity. Several studies have indicated a link between cholesterol and Alzheimer's disease (AD), and there is also epidemiological evidence that statin treatment may decrease the prevalence of dementias. In the present study we wanted to investigate whether pravastatin treatment affects brain cholesterol metabolism. METHODS: A post hoc analysis was performed with plasma material from a clinical trial where 51 healthy men (35+/-4 years) were randomly assigned to receive either pravastatin (40 mg/day) or placebo for 6 months. Cholesterol, its precursor lathosterol, its brain-specific metabolite 24(S)-hydroxycholesterol (24S-OH-chol) and 27-hydroxycholesterol (27-OH-chol) were determined in plasma samples before and after treatment by using gas-liquid chromatography (GC)-flame ionization detection (GC-FID) and GC mass spectrometry (GC-MS). RESULTS: Besides reducing total cholesterol (-20%, P<0.001) and LDL cholesterol (LDL-C; -33%, P<0.001) concentrations, pravastatin treatment resulted in a decrease of the ratio of lathosterol to cholesterol, a surrogate marker of endogenous cholesterol synthesis, by 20% (P<0.05). Absolute concentrations of 24S-OH-chol were not altered, but its ratio to cholesterol slightly increased by 15% (P<0.05). 27-OH-chol concentrations as well as its ratio to cholesterol were both significantly altered due to pravastatin treatment (-7% and +14%, P<0.05 for both, respectively). CONCLUSIONS: The treatment with pravastatin 40 mg once a day for 6 months does not affect brain cholesterol metabolism as judged by plasma concentrations of 24(S)-hydroxycholesterol.

The influence of hepatic lipase C-480T polymorphism on coronary flow reserve in young men is independent of the plasma cholesterol level.

BACKGROUND: The hepatic lipase (HL) gene C-480T promoter polymorphism affects gene transcription and enzyme activity and leads to CC, CT, and TT genotypes. Recently, HL expression was detected in macrophages. It has been postulated that HL might have a direct role in the pathogenesis of atherosclerosis without changes in the plasma profile. We hypothesized that the difference of plasma cholesterol level may not influence the effect of HL genotype on coronary reactivity. METHODS: A total of 108 young men (aged 34+/-5 years) were genotyped and divided into three groups. These groups contained 45, 49 and 14 men having either normal (4.9+/-1.2 mmol/L), mildly (5.5+/-0.8 mmol/L) or severely (7.8+/-1.9 mmol/L, subjects with familial hypercholesterolemia) elevated mean plasma cholesterol level, respectively. Myocardial blood flow (MBF) was measured at rest and during adenosine or dipyridamole-induced hyperemia with positron emission tomography using [(15)O] H(2)O. RESULTS: The effect of HL genotype on the indices of MBF was parallel within all cholesterol groups and therefore they were combined. In all subjects, basal flow did not differ between the genotypes. However, men with CC genotype had a significantly higher hyperemic blood flow (3.86+/-1.26 mLg(-1)min(-1) versus 3.20+/-1.38 mLg(-1)min(-1), p=0.007), higher coronary flow reserve (CFR, 4.80+/-1.77 versus 3.77+/-1.43, p=0.001) and lower coronary resistance during hyperemia (25.63+/-9.98 mmHg min g mL(-1) versus 35.00+/-23.95 mmHg min g mL(-1), p=0.003) than T allele carriers. In multivariate regression analysis, after adjustment for age, body mass index, serum lipids, blood pressure, adenosine or dipyridamole administration, and study group, HL polymorphism was an independent predictor of blood flow during hyperemia (p=0.016), coronary resistance (p=0.014), and CFR (p=0.005), respectively. CONCLUSIONS: The HL C-480 T polymorphism is associated with CFR, which is an early indicator of atherosclerosis, independently of the level of plasma cholesterol in young men.

Self-monitoring of blood pressure promotes achievement of blood pressure target in primary health care.

BACKGROUND: The majority of hypertensive patients do not reach the target blood pressure (BP). We sought to clarify whether intermittent self-monitoring of BP leads to better BP control compared to ordinary treatment in general practice. METHODS: Two hundred sixty-nine hypertensive patients participated in this multicenter, randomized, parallel-group study in primary health care. Home BP was measured in the self-monitoring (SM) group at 0, 2, 4, and 6 months, and in the control (C) group at 0 and 6 months. The participating physicians were instructed to intensify the antihypertensive therapy when needed. RESULTS: At the beginning, both groups had similar home BP levels (SM 143.1 +/- 17.4/85.3 +/- 7.4 mm Hg v C 143.9 +/- 18.3/85.4 +/- 7.5 mm Hg). After 6 months, there were significant decreases in systolic (P

Transthoracic Doppler echocardiography as a noninvasive tool to assess coronary artery stenoses--a comparison with quantitative coronary angiography.

We prospectively tested the diagnostic accuracy of Doppler transthoracic echocardiography in detection of coronary artery stenoses throughout the main coronary arterial tree. In all, 84 patients referred for diagnostic quantitative coronary angiography were studied. Coronary artery stenosis was identified with color Doppler as local spot of turbulence, and local flow velocity was measured using pulsed wave Doppler. Angiography showed significant stenoses (diameter reduction > 50%) in 33 patients. An abnormal maximal-to-prestenotic blood flow velocity ratio greater than 2.0 in subtotal stenoses, or the detection of collateral blood flow in the absence of normal antegrade flow in the case of total occlusion (N = 6), resulted in overall sensitivity of 82% and specificity of 92%. The sensitivity and specificity were, respectively, 73% and 92% for left anterior descending coronary artery, 63% and 96% for right coronary artery, and 38% and 99% for left circumflex coronary artery stenoses. Transthoracic echocardiography is a promising noninvasive technique to diagnose significant coronary artery stenoses.

Bell or diaphragm in the measurement of blood pressure?

BACKGROUND: International guidelines have given diverse recommendations as to which side of the stethoscope should be used in the measurement of blood pressure. OBJECTIVE: To determine if there is any difference between the bell and the diaphragm sides of the ordinary acoustic stethoscope in the measurement of blood pressure. DESIGN AND METHODS: We compared, in random order, the bell and the diaphragm side of the ordinary acoustic stethoscope and also the effect of low- and high-frequency amplification with an electronic stethoscope in the measurement of blood pressure, in 250 adults. SETTING: Department of Medicine, Turku University Central Hospital. RESULTS: No statistically significant difference was seen between the bell side and the diaphragm side of the acoustic stethoscope, either in systolic blood pressure (SBP; mean +/- SD 129.5 +/- 21.7 and 129.4 +/- 20.8 mmHg, respectively) or diastolic blood pressure (DBP; 77.0 +/- 12.0 and 77.1 +/- 12.0 mmHg, respectively). Both the low-frequency (130.7 +/- 22.5 mmHg) and the high-frequency (131 +/- 22.2 mmHg) amplification of systolic Korotkoff sounds yielded significantly greater values of SBP than were measured either with the bell (P = 0.008 compared with low frequency, P = 0.0005 compared with high frequency) or the diaphragm (P = 0.004 compared with low frequency, P = 0.0001 compared with high frequency). Low-frequency amplification of DBP (76.4 +/- 12.3 mmHg) yielded values significantly lower than those measured with the bell (P = 0.04) or the diaphragm (P = 0.01). Values from high-frequency amplification of DBP (77.2 +/- 12.3 mmHg) did not differ significantly from those measured with the acoustic stethoscope. CONCLUSIONS: Both sides of the acoustic stethoscope give similar results in the measurement of office blood pressure and either side can be used in the reliable measurement of blood pressure.

Estrogen receptor genotype modulates myocardial perfusion in young men.

Most of the effects of estrogens are mediated by estrogen receptors. Vascular endothelial cells and smooth muscle cells express estrogen receptor alpha (ESR1) in both genders. A long genotype group of a common thymine-adenine (TA) dinucleotide repeat polymorphism in the regulatory region of this gene has previously been related to coronary artery disease. The present study examined whether coronary blood flow is affected by this genotype. A total of 49 healthy men were genotyped by PCR and divided into three groups according to median number of the ESR1 promoter TA repeat (=19), i.e., in the short allele genotype group both alleles were of fewer than 19 repeats whereas in the long allele group both alleles were 19 repeats or more. The intermediate group comprised men who had one short and one long allele. Myocardial blood flow was measured by positron emission tomography using [(15)O]water, performed at rest and during adenosine stimulation. Men with long alleles had lower adenosine-stimulated coronary flow than those with short alleles and those with one short and one long allele. Our results suggest that adenosine-stimulated myocardial perfusion is lower in subjects with ESR1 long alleles than the other TA repeat genotypes.

The effect of mannan-binding lectin variant alleles on coronary artery reactivity in healthy young men.

Mannan-binding lectin (MBL) is a serum acute-phase protein and a complement component secreted by the liver. Its deficiency caused by point mutations in the MBL gene has recently been associated with severe atherosclerosis. In this study, we investigated the effect of MBL variant alleles on coronary artery reactivity, which is an early marker of coronary dysfunction and predicts the development of atherosclerosis and coronary artery disease. The study population consisted of 51 apparently healthy, normo- or mildly hypercholesterolemic young men. Myocardial blood flow was measured at baseline and during adenosine-induced hyperemia with positron emission tomography (PET), and MBL genotyping was performed using restriction fragment-length polymorphism. As a result, MBL variant alleles had no effect on coronary artery reactivity. This finding suggests that MBL deficiency is not an independent risk factor for coronary dysfunction and early atherogenic changes but rather a co-factor in the development of atherosclerosis. Thus, the connection of MBL variant alleles with environmental risk factors in atherosclerosis should further be assessed.