Differential impacts of 24 hour urinary sodium excretion on cardiovascular diseases or cancer mortality in a general population.

BACKGROUND: Elevated blood pressure is a major risk factor for cardiovascular (CV) disease. But the effects of sodium intake or excretion on CV mortality are uncertain. The present study aimed to investigate the association between 24 h urinary sodium excretion, as a marker of dietary salt intake, and CV or cancer mortality in a healthy Japanese population using 24 hurine collection. METHODS: The baseline study was conducted in 1980. A total of 1291 participants aged 21 to 85 years, underwent health check-ups, which included blood chemistry measurements and the collection of 24 h urine samples. Enrolled 1291 participants were followed up for 27.5 years, in whom the final follow-up rate was 95.8%. Cox proportional hazards regression models were used to assess the association between 24 h urinary sodium excretion and CV or cancer mortality. RESULTS: The mean 24 h urinary sodium excretion was 5.80 ± 2.28 g/day. There were 631 deaths: 153 (27%) from cancer, 142 (26%) from CV disease. In the Cox proportional hazard regression model after adjustment for confounding factors, systolic and diastolic blood pressures, and uric acid were positively associated with CV mortality, and the 24 h urinary sodium and potassium excretions were inversely associated with CV mortality (p < 0.05). On the other hand, there were no association between 24 h urinary sodium excretions and cancer mortality. We divided the urinary sodium excretions levels into quartiles. After adjustment for confounding factors, the hazard ratio of CV mortality in the highest quartile of 24 h urinary sodium excretion versus the lowest was 0.46 (p < 0.05). The cumulative survival rate for CV death was significantly decreased in the lowest quartile compared with the other higher groups. CONCLUSIONS: We found that impacts of 24 h sodium excretion on CV and cancer mortalities were much different in the general population.

Impact of combined elevations of homocysteine and asymmetric dimethylarginine on all-cause death - The Tanushimaru Study.

BACKGROUND: Both homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) induce endothelial dysfunction. However, the impact of both elevations on all-cause death is not known. We investigated the association between elevations of Hcy or ADMA and all-cause death in a general population. METHODS: A total of 517 subjects (224 men, 293 women; mean age, 62.8 years) were recruited from a population-based survey in 1999 in Tanushimaru, and we measured fasting plasma Hcy and ADMA levels. We followed them up for over 20 years and examined the effect on mortality using Cox proportional hazard regression model. RESULTS: The mean follow-up years were 17.7 (1.8-20.8). In this period, 182 subjects have died (35.2%). The correlation between Hcy and ADMA was high (r=0.194; p<0.001). With Cox regression analysis after adjustments for age and sex, elevated log transformed Hcy levels were significantly associated with all-cause death (p=0.028). When Hcy and ADMA levels were divided into quintiles, the hierarchical model showed the synergistic effect of Hcy and ADMA on all-cause death. CONCLUSIONS: This is the first report that we have measured Hcy and ADMA levels simultaneously in this community-dwelling Japanese, and we demonstrated that combined elevations of Hcy and ADMA had big impact on all-cause death in this epidemiological study.

Lower albumin levels are associated with frailty measures, trace elements, and an inflammation marker in a cross-sectional study in Tanushimaru.

BACKGROUND: There is little data on the association between the lower nutrition represented by serum albumin levels and related factors in a general population. The present study aimed to determine whether the albumin level positioned as some kind of biomarker with frailty measures, trace elements, and an inflammation marker. METHODS: In 2018, we performed an epidemiological survey in 1368 subjects who resided in Tanushimaru, Japan, in which we examined the blood chemistry including albumin, trace elements, hormone levels, and carotid ultrasonography. Albumin levels were categorized into 4 groups (G1 [3.2-3.9 mg/dL], G2 [4.0-4.3 mg/dL], G3 [4.4-4.6 mg/dL], and G4 [4.7-5.3 mg/dL]). The participants underwent measurements of handgrip strength and were tested by asking to walk 5 m. Their cognitive functions were evaluated by the mini-mental state examination (MMSE). RESULTS: Multiple stepwise regression analysis demonstrated that albumin levels were significantly and independently associated with age (inversely), systolic blood pressures, estimated glomerular filtration rate (eGFR), MMSE score, frailty measures (handgrip strength), an inflammation marker (high-sensitivity C-reactive protein), hormones (growth hormone (inversely) and insulin-like growth factor-1), and trace elements (calcium, magnesium, iron, and zinc), with a linear trend. CONCLUSIONS: Lower albumin levels, even in the normal range, were found to be related factors of frailty measures, trace elements, and an inflammation marker in a general population.

Serum Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is Independently Associated with Insulin Resistance, Triglycerides, Lipoprotein(a) Levels but not Low-Density Lipoprotein Cholesterol Levels in a General Population.

AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as an important regulator of low-density lipoprotein (LDL) receptor processing. Evolocumab and alirocumab are PCSK9 inhibitors; however, little is known about the association between PCSK9 levels and lipid profiles in a general population. Because PCSK9 inhibitors have LDL-C lowering effects, we investigated whether there is a positive correlation between serum PCSK9 levels and LDL-C or lipoprotein(a) [Lp(a)]. METHODS: In Uku town, 674 residents (mean age; 69.2±8.3 years) received health check-ups. The participants underwent a physical examination and blood tests, including PCSK9 and Lp(a). Serum PCSK9 and Lp(a) were measured by ELISA and Latex methods, respectively. HOMA-IR was calculated by fasting plasma glucose×insulin levels/405. RESULTS: The mean (range) of PCSK9 and Lp(a) were 211.2 (49-601) ng/mL and 60 (1-107) mg/dL, respectively. Because of a skewed distribution, the log-transformed values were used. With univariate linear regression analysis, PCSK9 levels were associated with Lp(a) (p=0.028), triglycerides (p＜0.001), and HOMA-IR (p＜0.001), but not with LDL-C (p=0.138) levels. Multiple stepwise regression analysis revealed that serum PCSK9 levels were independently associated with triglycerides (p＜0.001), Lp(a) (p=0.033) and HOMA-IR (p=0.041). CONCLUSIONS: PCSK-9 is independently associated with triglycerides, Lp(a) levels, and HOMA-IR, but not LDL-C, in a relatively large general population sample.

Association between growth hormone and hypertension in a general population.

Insulin-like growth factors are polypeptides, with arrays similar to insulin, and insulin-like growth factor 1 (IGF-1) is secreted via stimulation by growth hormone (GH) in the liver. The lack of both GH and IGF-1 leads to physiological age-related changes in the cardiovascular system; however, the role of IGF-1 and GH in hypertension has not been fully elucidated. Thus, we examined the association between plasma IGF-1 and GH levels and hypertension. Among 1368 health check-up examination participants in the town of Tanushimaru, 1094 subjects were analyzed after excluding subjects with diabetes mellitus or impaired liver function. Multiple linear and logistic regression analyses were performed for factors related to systolic and diastolic blood pressures (BPs). Characteristics of participants stratified by IGF-1 and GH quartiles were compared using analysis of covariance. We calculated odds ratios associated with each standard deviation increase in IGF-1 and GH levels for hypertension, which was defined as BP ≥ 140/90 mmHg and/or the use of antihypertensive medication. Multivariable analysis showed that FPG, insulin, HOMA-IR, eGFR, total cholesterol, triglycerides, and the use of medication for hypertension were associated with the Z-score of IGF-1 measurement quartiles. Next, we found that BMI, systolic and diastolic BPs, insulin, HOMA-IR, total cholesterol, HDL-cholesterol, triglycerides, smoking, and alcohol intake were associated with GH quartiles, indicating that hypertension was inversely associated with GH but not IGF-1. A significant and inverse relationship between serum GH and hypertension was found after adjustment for confounders. In conclusion, decreased GH but not IGF-1, was associated with hypertension in a general population.

Trends in nutritional intake and coronary risk factors over 60 years among Japanese men in Tanushimaru.

We investigated the relationship between time trends in nutrient intake and coronary risk factors/mortality rates in Tanushimaru, a Japanese cohort of the Seven Countries Study. All men between the ages of 40 and 64 were enrolled. Subjects numbered 628 in 1958, 539 in 1977, 602 in 1982, 752 in 1989, 402 in 1999, 329 in 2009, and 160 in 2018. Eating patterns were evaluated by 24-h dietary recall from 1958 through 1989, and by a food frequency questionnaire administered from 1999 through 2018. The total daily energy intake decreased from 2,837 kcal in 1958 to 2,096 kcal in 2018. Carbohydrate intake as a percentage of the total decreased remarkably from 84% (1958) to 53% (2018), whereas there was a large increase in fat intake (from 5 to 24%) during the same period. Age-adjusted mean cholesterol levels rose sharply (from 167.9 to 209.4 mg/dl) and body mass index levels also increased (from 21.7 to 24.4 kg/m2), but smoking rate decreased from 69% (1958) to 30% (2018). The mortality rates from stroke and cancer declined, but mortality from myocardial infarction and sudden death remained stable at low levels. The remarkable changes in dietary patterns over the last 60 years can be related to coronary risk factors, but not currently to the mortality of coronary artery disease; more follow-up is needed.

Habitual coffee intake reduces all-cause mortality by decreasing heart rate.

It is well known that subjects with metabolic syndrome show an elevated resting heart rate. We previously reported that elevated heart rate was significantly related to all-cause mortality, and that coffee consumption was inversely associated with metabolic syndrome. We hypothesized that higher coffee consumption may decrease all-cause mortality by reducing resting heart rate. We performed a longitudinal epidemiological study in Tanushimaru (a cohort of the Seven Countries Study). A total of 1920 residents aged over 40 years received health checkups in 1999. We measured components of metabolic syndrome, and eating and drinking patterns were evaluated by a food frequency questionnaire. We followed up the participants annually for 15 years. During the follow-up period, 343 of the participants died. Of these, 102 subjects died of cancer, 48 of cerebro-cardiovascular diseases, and 44 of infectious diseases. Multivariate analyses revealed that higher coffee consumption was inversely associated with resting heart rate. Kaplan-Meier curves found lower mortality rates in the higher coffee consumption groups. In the lower coffee consumption groups, elevated hazard ratios of all-cause death were observed in the increased heart rate quintiles, whereas heart rate was not associated with all-cause death in the higher coffee consumption groups. These significant associations remained after further adjustment for confounders. This prospective study suggests that higher coffee consumption may have a protective effect against all-cause death due to reducing resting heart rate.

Coronary artery stent dislodgement and aortic dissection in a patient with a severely calcified lesion in the proximal right coronary artery.

In atherosclerosis progression, calcium deposition may have an impact on the natural history of coronary atherosclerosis, and the amount of calcium may affect the success rate of percutaneous coronary intervention (PCI). Coronary stent dislodgement does not commonly occur in the modern PCI era; however, it may lead to fatal death. If it occurs, retrieval of a dislodged stent can be performed either surgically or percutaneously using a variety of retrieval techniques, including inflating a catheter balloon distal to the undeployed stent, twirling 2 wires around the stent, a loop snare, or forceps. Here, we report a rare case that coronary artery stent dislodgement and aortic dissection simultaneously occurred during PCI for a severely calcified lesion in the proximal right coronary artery with shepherd's crook morphology. The situation was successfully rectified by using balloons to deploy the stent, as well as by applying an additional stent and minimizing the contrast used to treat aortic dissection. Learning objective: During percutaneous coronary intervention (PCI), stent dislodgement and aortic dissection are extremely rare, but life-threatening complications. In this rare case of simultaneous stent dislodgement in the coronary artery and aortic dissection during PCI for a severely calcified lesion in the right coronary artery with shepherd's crook morphology, the situation was successfully rectified by using balloons to retrieve and deploy the stent, as well as by applying an additional stent and minimizing the contrast used to treat aortic dissection.