Antihypertensives and Statin Therapy for Primary Stroke Prevention

Background and Purpose: The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups. Methods: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed. Results: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59–1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55–1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34–1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41–2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52–0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37–0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59–2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57–2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36–0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23–0.72]). Conclusions: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00468923.

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Impact of blood pressure lowering, cholesterol lowering and their combination in Asians and non-Asians in those without cardiovascular disease: an analysis of the HOPE 3 study

European Journal of Preventive Cardiology ◽

10.1177/2047487318819019 ◽

2018 ◽

Vol 26 (7) ◽

pp. 681-697 ◽

Cited By ~ 4

Author(s):

Prem Pais ◽

Hyejung Jung ◽

Antonio Dans ◽

Jun Zhu ◽

Lisheng Liu ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Primary Outcome ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Intermediate Risk ◽

Blood Pressure Lowering ◽

Low Density Lipoprotein Cholesterol ◽

Cholesterol Lowering ◽

Pressure Lowering

Background and design There are limited data on the effects of blood pressure and cholesterol lowering in Asians at intermediate risk and no cardiovascular disease. We report an analysis of the effects of blood pressure and cholesterol lowering in Asians enrolled in the Heart Outcomes Prevention Evaluation 3 (HOPE 3) trial. Methods We randomly assigned 6241 Asians and 6464 non-Asians at intermediate risk without cardiovascular disease to candesartan 16 mg/hydrochlorothiazide 12.5 mg or placebo and rosuvastatin 10 mg or placebo. The first co-primary outcome was a composite of cardiovascular disease death, myocardial infarction and stroke. The second co-primary outcome additionally included heart failure, cardiac arrest and revascularisation. Median follow-up was 5.6 years. Results Reduction in systolic blood pressure was less among Asians (4.3 vs. 7.7 mmHg for non-Asians, P < 0.0001) mainly due to a lesser effect in Chinese (2.1 mmHg) than in other Asians (7.3 mmHg), reduction in the latter being similar to non-Asians. The effect on the composite outcomes was similar, with no significant benefits from blood pressure lowering for either Asians (Chinese or non-Chinese) or non-Asians. Rosuvastatin reduced low-density lipoprotein cholesterol to a lesser degree in Asians (0.49 mmol/L (–19.1 mg/dL) compared with non-Asians 0.95 mmol/L (−36.7 mg/dL), Pinteraction < 0.0004). Yet both groups had similar reductions in the two co-primary outcomes. There was no increase in permanent medication discontinuation due to muscle-related symptoms in either group. There was an excess in new diabetes in non-Asians (4.70% rosuvastatin, 3.52% placebo, P = 0.025) but not in Asians (3.02% rosuvastatin, 4.04% placebo, P = 0.0342), Pinteraction = 0021. Conclusions Candesartan/hydrochlorothiazide had fewer effects in reducing blood pressure in Chinese and rosuvastatin reduced low-density lipoprotein cholesterol to a lesser extent in Asians compared with non-Asians. There was no overall reduction in clinical events with lowering blood pressure in either Asians or non-Asians, whereas there were clear and consistent benefits with lipid lowering in both. Despite extensive analyses, we have no obvious explanation for the observed findings. Future studies need to include larger numbers of individuals from different regions of the world to ensure that the results of trials are applicable globally.

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Effects of atorvastatin (and blood pressure lowering comparing amlodipide-based therapy with beta-blocker-based therapy) on serum variables of cholesterol synthesis and absorption, thrombogenicity and on low-density lipoprotein oxidation in vivo

Journal of Human Hypertension ◽

10.1038/sj.jhh.1001083 ◽

2001 ◽

Vol 15 (S1) ◽

pp. S27-S29 ◽

Cited By ~ 1

Author(s):

MS Nieminen ◽

J Viikari ◽

M Ahotupa ◽

T Vasankari ◽

I Kantola ◽

...

Keyword(s):

Blood Pressure ◽

Cholesterol Synthesis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Blood Pressure Lowering ◽

Lipoprotein Oxidation ◽

Pressure Lowering ◽

Low Density Lipoprotein Oxidation

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Risk factors for cardiovascular diseases and development of prehypertension

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2018.03.37-43 ◽

2018 ◽

pp. 37-43

Author(s):

В.В. Шерстнев ◽

М.А. Грудень ◽

В.П. Карлина ◽

В.М. Рыжов ◽

А.В. Кузнецова ◽

...

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Cardiovascular Disease ◽

Ldl Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Serum Levels ◽

Left Ventricular ◽

Optimal Blood Pressure

Цель - исследование взаимосвязи факторов риска сердечно-сосудистых заболеваний и развития предгипертонии. Методика. Проведен сравнительный и корреляционный анализы показателей модифицируемых и немодифицируемых факторов риска сердечно-сосудистых заболеваний у обследованных лиц в возрасте 30-60 лет с «оптимальным» артериальным давлением, (n = 63, АД <120/80 мм рт.ст.) и лиц с предгипертонией (n = 52, АД = 120-139/80-89 мм рт.ст.). Результаты. Показано, что лица с предгипертонией по сравнению с группой лиц, имеющих «оптимальное» артериальное давление характеризуются статистически значимо повышенным содержанием холестерина и холестерина липопротеидов низкой плотности, интеллектуальным характером трудовой деятельности, а также значимыми сочетаниями факторов риска: повышенный уровень холестерина липопротеидов низкой плотности с интеллектуальным характером трудовой деятельности; повышенное содержание креатинина с уровнем триглициридов; наследственная отягощенность по заболеваниям почек и интеллектуальным характером трудовой деятельности; наследственная отягощенность по сахарному диабету и гипертрофия левого желудочка сердца. У лиц с предгипертонией документированы перестройки структуры взаимосвязи (количество, направленность и сила корреляций) между показателями факторов риска в сравнении с лицами, имеющими «оптимальное» артериальное давление. Заключение. Выявленные особенности взаимосвязей факторов риска сердечно-сосудистых заболеваний при предгипертонии рассматриваются как проявление начальной стадии дизрегуляционной патологии и нарушения регуляции физиологических систем поддержания оптимального уровня артериального давления. The aim of the study was to investigate the relationship between risk factors for cardiovascular disease and development of prehypertension. Methods. Comparative and correlation analyses of modifiable and non-modifiable risk factors for cardiovascular disease were performed in subjects aged 30-60 with «optimal» blood pressure (n = 63, BP <120/80 mm Hg) and prehypertension (n = 52, BP = 120-139 / 80-89 mm Hg). Results. The group with prehypertension compared with the «optimal» blood pressure group had significantly increased serum levels of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, sedentary/intellectual type of occupation, and significant combinations of risk factors. The risk factor combinations included an increased level of LDL cholesterol and a sedentary/intellectual occupation; increased serum levels of creatinine and triglycerides; hereditary burden of kidney disease and a sedentary/intellectual occupation; hereditary burden of diabetes mellitus and cardiac left ventricular hypotrophy. In subjects with prehypertension compared to subjects with «optimal» blood pressure, changes in correlations (correlation number, direction, and strength) between parameters of risk factors were documented. Conclusion. The features of interrelationships between risk factors for cardiovascular disease observed in prehypertension are considered a manifestation of early dysregulation pathology and disordered regulation of physiological systems, which maintain optimal blood pressure.

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Faculty Opinions recommendation of Effect of intensive blood pressure lowering on cardiovascular outcomes based on cardiovascular risk: A secondary analysis of the SPRINT trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734084254.793578582 ◽

2020 ◽

Author(s):

Costas Tsioufis

Keyword(s):

Blood Pressure ◽

Cardiovascular Risk ◽

Secondary Analysis ◽

Cardiovascular Outcomes ◽

Blood Pressure Lowering ◽

Pressure Lowering ◽

Intensive Blood Pressure

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The neurological level of spinal cord injury and cardiovascular risk factors: a systematic review and meta-analysis

Spinal Cord ◽

10.1038/s41393-021-00678-6 ◽

2021 ◽

Author(s):

Peter Francis Raguindin ◽

Gion Fränkl ◽

Oche Adam Itodo ◽

Alessandro Bertolo ◽

Ramona Maria Zeh ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Blood Pressure ◽

Spinal Cord ◽

Cardiovascular Risk ◽

Meta Analysis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Cord Injury

Abstract Study design Systematic review and meta-analysis. Objective To determine the difference in cardiovascular risk factors (blood pressure, lipid profile, and markers of glucose metabolism and inflammation) according to the neurological level of spinal cord injury (SCI). Methods We searched 5 electronic databases from inception until July 4, 2020. Data were extracted by two independent reviewers using a pre-defined data collection form. The pooled effect estimate was computed using random-effects models, and heterogeneity was calculated using I2 statistic and chi-squared test (CRD42020166162). Results We screened 4863 abstracts, of which 47 studies with 3878 participants (3280 males, 526 females, 72 sex unknown) were included in the meta-analysis. Compared to paraplegia, individuals with tetraplegia had lower systolic and diastolic blood pressure (unadjusted weighted mean difference, −14.5 mmHg, 95% CI −19.2, −9.9; −7.0 mmHg 95% CI −9.2, −4.8, respectively), lower triglycerides (−10.9 mg/dL, 95% CI −19.7, −2.1), total cholesterol (−9.9 mg/dL, 95% CI −14.5, −5.4), high-density lipoprotein (−1.7 mg/dL, 95% CI −3.3, −0.2) and low-density lipoprotein (−5.8 mg/dL, 95% CI −9.0, −2.5). Comparing individuals with high- vs. low-thoracic SCI, persons with higher injury had lower systolic and diastolic blood pressure (−10.3 mmHg, 95% CI −13.4, −7.1; −5.3 mmHg 95% CI −7.5, −3.2, respectively), while no differences were found for low-density lipoprotein, serum glucose, insulin, and inflammation markers. High heterogeneity was partially explained by age, prevalent cardiovascular diseases and medication use, body mass index, sample size, and quality of studies. Conclusion In SCI individuals, the level of injury may be an additional non-modifiable cardiovascular risk factor. Future well-designed longitudinal studies with sufficient follow-up and providing sex-stratified analyses should confirm our findings and explore the role of SCI level in cardiovascular health and overall prognosis and survival.

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Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease

New England Journal of Medicine ◽

10.1056/nejmoa1600175 ◽

2016 ◽

Vol 374 (21) ◽

pp. 2009-2020 ◽

Cited By ~ 350

Author(s):

Eva M. Lonn ◽

Jackie Bosch ◽

Patricio López-Jaramillo ◽

Jun Zhu ◽

Lisheng Liu ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Intermediate Risk ◽

Blood Pressure Lowering ◽

Pressure Lowering

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Association of Blood Pressure Lowering With Mortality and Cardiovascular Disease Across Blood Pressure Levels

JAMA Internal Medicine ◽

10.1001/jamainternmed.2017.6015 ◽

2018 ◽

Vol 178 (1) ◽

pp. 28 ◽

Cited By ~ 118

Author(s):

Mattias Brunström ◽

Bo Carlberg

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Blood Pressure Lowering ◽

Pressure Lowering

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Gender Difference in Blood Pressure Control and Cardiovascular Risk Factors with Diagnosed Hypertension

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i56a33911 ◽

2021 ◽

pp. 275-280

Author(s):

Tarique Shahzad Chachar ◽

Ummama Laghari ◽

Ghullam Mustafa Mangrio ◽

Abdul Ghaffar Dars ◽

Ruqayya Farhad ◽

...

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Pressure Control ◽

Health Sciences ◽

Low Density Lipoprotein Cholesterol ◽

Male And Female

Objective: Our study was designed to compare the gender difference in Blood Pressure Control and Cardiovascular Risk Factors in patients of Liaquat University of Medical and Health Sciences Jamshoro Pakistan. Methodology: This cross-sectional study was conducted in Liaquat University of Medical and Health Sciences Jamshoro Pakistan from December 2019 to December 2020. Blood pressure was measured twice by trained physicians using aneroid sphygmomanometers after a standardized protocol. Patients were asked to sit with both feet on the floor for ≥5 minutes before the first BP measurement. Both the two BP measurements were taken 60 seconds apart. For this research we defined hypertension as systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg. Results: We conducted a comparison between Hypertensive and nonhypertensive participants of the male and female groups. High blood pressure increased the level of uric acid in both male and female groups (351 ± 92 vs 303 ± 75). We observed that the hypertensive male population reported a high prevalence of cardiovascular risk factors due to increase amount of total cholesterol level, triglyceride and low-density lipoprotein cholesterol (5.45 ± 1.01, 1.42 ± 0.85, 2.56 ± 0.70) than females (5.15 ± 0.91, 1.29 ± 0.87, 2.30 ± 0.63). Conclusion: Our results concluded that the male hypertensive population is more prone to future cardiovascular risk due to increased amount of total cholesterol levels, triglycerides, and low-density lipoprotein cholesterol, and sex hormones (androgens).

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